Alcohol DependencePhase 2NCT01631630

Role of Proinflammatory Signaling in Alcohol Craving

A Phase 2 study testing Pioglitazone in people with Alcohol Dependence and Alcohol Drinking, run by National Institute on Alcohol Abuse and Alcoholism (NIAAA) at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

Search all trials

Trial summary

Background: Drinking too much alcohol can injure cells in the body. Inflammation is the body s reaction to injured cells. Studies show that inflammation can cause cravings for alcohol. Researchers want to see if pioglitazone, a drug that decreases inflammation, can reduce alcohol craving. Read more about this study

Who is it for?: Ages 21 to 65 years
Conditions the study is for: Alcohol Dependence, Alcohol Drinking, Stress
What is being tested?: Pioglitazone
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 16 participants
Where: 1 siteUnited States
Study dates: May 2012to Sep 2015
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 21 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Diagnostic and Statistical Manual (DSM)-IV diagnosis of alcohol dependence on Structured Clinical Interview for DSM Diagnosis (SCID) alcohol problems as primary complaint among substance use disorders, and alcohol use within the last month.
Age 21 65
Right handed
For women:
post-menopausal or surgically sterile (tubal ligation or hysterectomy); or
if sexually active with a male partner and able to get pregnant, documented agreement to use an effective form of birth control. Acceptable forms of contraception for this study include: hormonal contraceptives (birth-control pills, injectable hormones, vaginal-ring hormones); intrauterine device (IUD); diaphragm with spermicide; condom with spermicide.

Who cannot join

Any medical illness that in the view of the investigators would compromise participation in research, as determined by medical history, physical examination, laboratory tests (see details under Screening measures below), including, but not limited to:
Diabetes mellitus Type I or Type II
Past or current diagnosis of congestive heart failure
Signs and symptoms suggestive of congestive heart failure
Cardiovascular disease (e.g., history of congenital heart defect, heart disease, symptomatic coronary-artery disease, heart attack, clinically significant arrhythmia, etc.)
Cerebrovascular disease

Show all 29Show fewer

Infection, autoimmune disease, or fever of unknown origin
Unexplained history of syncope
History of seizures, except for febrile seizures during childhood
History of head injury with loss of consciousness of more than 30 minutes or with postconcussive sequelae lasting more than two days, regardless of loss of consciousness
Chronic renal failure as estimated by glomerular filtration rate (GFR) <60 milliliters per minute 1.73 per Square
HIV infection
Active bladder cancer, history of bladder cancer, or persistent hematuria
Allergy, hypersensitivity, or intolerance to pioglitazone, other thiazolidinediones, or the metabolites of any of those drugs (determined by medical history)
Pregnancy or breastfeeding (urine pregnancy test; self-report)
Diabetes medications (e.g., sulfonylureas, metformin, insulin, etc.)
Contraindicated or strongly interacting medications: Gemfibrozil (inhibitor of CYP2C8) and rifampin (inducer of CYP2C8), atorvastatin, ketoconazole, nifedipine
Any ongoing, or regular use of central nervous system (CNS) active medications within the last week (fluoxetine: last 4 weeks), with the exception of withdrawal medication, obtained according to the NIAAA clinical guidelines if needed
Use of docosahexaenoic acid (DHA) dietary supplements, or consumption of oily fish >3 times per week (because of effects of DHA on inflammatory parameters)
History of Rhabdomyolysis
Psychiatric history:
Cognitive impairment severe enough to preclude informed consent or valid responses on questionnaires, as established by clinical exam, in questionable cases aided by a Mini Mental State Examination (with a score of <21, indicating more than mild cognitive impairment, being exclusionary)
Current diagnosis of schizophrenia or any other DSM-IV psychotic disorder, bipolar disorder, or major depressive disorder, in each case as established by clinical evaluation and SCID.
Substance use disorders:
Current alcohol intoxication on breathalyzer test or positive urine drug screen on enrollment
Current dependence on drugs other than alcohol or nicotine, as established by SCID interview
Inability or unwillingness to participate in an fMRI scan, including
Presence of ferromagnetic objects in the body that are contraindicated for MRI of the head (pacemakers or other implanted electrical devices, brain stimulators, some types of dental implants, aneurysm clips, metallic prostheses, permanent eyeliner, implanted delivery pump, or shrapnel fragments) or fear of enclosed spaces. Eligibility will be determined by a MRI Safety Screening Questionnaire and verified, if necessary, by a physician.
Subjects that cannot lie comfortably flat on their back for up to 2 hours in the MRI scanner.

Trial locations and contacts

1 site in 1 country.

United States1 site

National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892

Other trials in United States

About this study

Background:

Drinking too much alcohol can injure cells in the body. Inflammation is the body s reaction to injured cells. Studies show that inflammation can cause cravings for alcohol. Researchers want to see if pioglitazone, a drug that decreases inflammation, can reduce alcohol craving. If so, it might help develop new ways to help alcoholics with craving.

Objectives:

To see if pioglitazone can reduce alcohol craving.

Eligibility:

Adults between 21 and 65 years of age who are alcoholic and have been drinking within the past month.

Design:

Participants will be screened with a physical exam and medical history. Blood samples will also be collected.
All participants will have inpatient treatment at the National Institutes of Health Clinical Center for the 5 weeks of the study. They will have standard treatment for alcoholism during their inpatient stay.
Half of the people in this study will have pioglitazone. The other half will have a placebo.
Participants will have different studies during their stay. These studies will include the following:
Personalized audio recordings of stressful, alcohol-related, and neutral events to monitor mood
Imaging studies to test alcohol cravings
Questionnaires about mood and alcohol cravings
Lumbar puncture to collect spinal fluid
Inflammation test to see if the study drug can block alcohol cravings
After the end of the 5-week study, all participants will be offered follow-up outpatient care through the Clinical Center, or referral to outside treatment.

Read the detailed description

Objective: The objective of the present study is to evaluate the role of proinflammatory signaling in alcohol craving. The peroxisome proliferator-activated receptor y (PPARy) agonist pioglitazone, which modulates glial activity, will be used as an experimental treatment. Guided imagery auditory scripts will be used as an established set of stimuli to induce craving. Low dose lipopolysaccharide (LPS) administration which activates proinflammatory signaling will be used as a novel challenge, and evaluated for its ability to provoke alcohol craving. If LPS in fact induces alcohol craving, the present design will allow evaluation of whether pioglitazone can inhibit this response.

Study population: Up to 60 subjects will be recruited for a target accrual of 50 completers. Subjects will be aged 21-65 years, with alcohol dependence as their primary complaint, and without other serious medical or psychiatric conditions. They will be admitted to the NIAAA research inpatient unit at the NIH Clinical Research Center (CRC) through one of the screening protocols (05-AA-0121 Assessment and Treatment of People with Alcohol Drinking Problems ) or 14-AA-0181 "Unit and Clinic Evaluations, Screening, Assessment, and Management") which provides basic assessments and standard withdrawal treatment if needed.

Design: Following inclusion, subjects will undergo interviews for construction of guided imagery scripts, and these scripts will subsequently be used as stress-, alcohol- or neutral condition associated stimuli. Subjects will be randomized to pioglitazone (n=25; final dose: 45mg/daily) or identically looking placebo (n=25). Following at least two weeks of treatment, subjects will undergo three sessions of guided imagery, on separate days and in a counter-balanced order, exposing them to the personalized stress-, alcohol- or neutral condition associated auditory scripts, respectively. During the final week, subjects will undergo two challenge sessions, a minimum of five days apart, with lipopolysaccharide (LPS) or placebo, in counterbalanced order.

Outcome measures: Subjective ratings of mood, anxiety and craving will be obtained twice weekly throughout the study. During the challenge sessions that utilize psychological stimuli or LPS, subjective ratings of craving for alcohol, as well as ratings of negative emotions will be obtained. Lumbar puncture will be performed and cerebrospinal fluid (CSF) obtained to determine the effect of pioglitazone on levels of proinflammatory cytokines. Neuroendocrine, psychological and physiological measures will be collected for exploratory purposes. An fMRI scan will be obtained to evaluate the effect of pioglitazone on BOLD signal in response to emotionally salient visual cues.

Conditions: Alcohol Dependence, Alcohol Drinking, Stress, Alcohol-Related Disorders
Being tested: Pioglitazone, Placebo
Keywords: Alcohol, Alcohol Dependence, Alcohol Use, Nicotine Dependence, Nicotine
Medical subject headings: Alcoholism, Alcohol Drinking, Alcohol-Related Disorders, Tobacco Use Disorder

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PioglitazoneDrug
Also called Actos
Pioglitazone is a thiazolidinedione antidiabetic. It works by lowering blood sugar by making the cells of the body more sensitive to the action of insulin.
PlaceboDrug
Also called Sugar Pill
Placebo is an inactive tablet design to look exactly like pioglitazone

Study groups in NCT01631630
Study group	Role	What they receive
Pioglitazone	Experimental	Subjects received pioglitazone, 15mg/day for 3 days; 30mg day for 3 days; 45mg/day thereafter, for a minimum total of 13 days Receives: Drug: Pioglitazone
Placebo	Placebo comparator	Subjects received placebo on a similar dosing schedule, for a minimum total of 13 days Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Alcohol Craving in Response to the Alcohol Cue Script
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Measured: 15 minutes prior to the beginning of script presentation, which occurred on Day 21, 22, or 23 of the treatment period
Alcohol Craving in Response to the Alcohol Cue Script
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Measured: 5 minutes after the beginning of script presentation, which occurred on Day 21, 22, or 23 of the treatment period
Alcohol Craving in Response to the Alcohol Cue Script
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Measured: 15 minutes after the beginning of script presentation, which occurred on Day 21, 22, or 23 of the treatment period
Alcohol Craving in Response to the Alcohol Cue Script
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Measured: 30 minutes after the beginning of script presentation, which occurred on Day 21, 22, or 23 of the treatment period
Alcohol Craving in Response to the Alcohol Cue Script
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Measured: 45 minutes after the beginning of script presentation, which occurred on Day 21, 22, or 23 of the treatment period
Alcohol Craving in Response to the Alcohol Cue Script
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Measured: 60 minutes after the beginning of script presentation, which occurred on Day 21, 22, or 23 of the treatment period
Alcohol Craving in Response to the Alcohol Cue Script
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Measured: 75 minutes after the beginning of script presentation, which occurred on Day 21, 22, or 23 of the treatment period
Alcohol Craving in Response to the Alcohol Cue Script
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Measured: 90 minutes after the beginning of script presentation, which occurred on Day 21, 22, or 23 of the treatment period
Alcohol Craving in Response to the Lipopolysaccharide Challenge
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Measured: 15 minutes prior to the subject receiving an intravenous bolus of lipopolysaccharide, which occurred on Day 25 or Day 32 of the treatment period
Alcohol Craving in Response to the Lipopolysaccharide Challenge
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Measured: 1 hour after the subject received an intravenous bolus of lipopolysaccharide, which occurred on Day 25 or Day 32 of the treatment period
Alcohol Craving in Response to the Lipopolysaccharide Challenge
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Measured: 2 hours after the subject received an intravenous bolus of lipopolysaccharide, which occurred on Day 25 or Day 32 of the treatment period
Alcohol Craving in Response to the Lipopolysaccharide Challenge
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Measured: 3 hours after the subject received an intravenous bolus of lipopolysaccharide, which occurred on Day 25 or Day 32 of the treatment period
Alcohol Craving in Response to the Lipopolysaccharide Challenge
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Measured: 4 hours after the subject received an intravenous bolus of lipopolysaccharide, which occurred on Day 25 or Day 32 of the treatment period
Alcohol Craving in Response to the Lipopolysaccharide Challenge
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Measured: 5 hours after the subject received an intravenous bolus of lipopolysaccharide, which occurred on Day 25 or Day 32 of the treatment period
Alcohol Craving in Response to the Lipopolysaccharide Challenge
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Measured: 6 hours after the subject received an intravenous bolus of lipopolysaccharide, which occurred on Day 25 or Day 32 of the treatment period
Alcohol Craving in Response to the Stress Script
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Measured: 15 minutes prior to the beginning of script presentation, which occurred on Day 21, 22, or 23 of the treatment period
Alcohol Craving in Response to the Stress Script
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Measured: 15 minutes after the beginning of script presentation, which occurred on Day 21, 22, or 23 of the treatment period
Alcohol Craving in Response to the Stress Script
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Measured: 5 minutes after the beginning of script presentation, which occurred on Day 21, 22, or 23 of the treatment period
Alcohol Craving in Response to the Stress Script
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Measured: 30 minutes after the beginning of script presentation, which occurred on Day 21, 22, or 23 of the treatment period
Alcohol Craving in Response to the Stress Script
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Measured: 45 minutes after the beginning of script presentation, which occurred on Day 21, 22, or 23 of the treatment period
Alcohol Craving in Response to the Stress Script
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Measured: 60 minutes after the beginning of script presentation, which occurred on Day 21, 22, or 23 of the treatment period
Alcohol Craving in Response to the Stress Script
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Measured: 75 minutes after the beginning of script presentation, which occurred on Day 21, 22, or 23 of the treatment period
Alcohol Craving in Response to the Stress Script
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Measured: 90 minutes after the beginning of script presentation, which occurred on Day 21, 22, or 23 of the treatment period

Secondary outcomes (30)

Anxiety Symptom Ratings Measured Bi-weekly During the Treatment Period
Anxiety symptoms were measured using the Comprehensive Psychopathological Rating Scale (CPRS). The CPRS is an 18-item interview-based instrument for assessing depression and anxiety. There are two 10-item subscales, the Montgomery-Asberg Depression Rating Scale (MADRS) and the Brief Scale for Anxiety (BSA). Each subscale ranges from 0 (lowest symptom severity) to 60 (highest symptom severity).
Measured: Day 1 of the treatment period
Anxiety Symptom Ratings Measured Bi-weekly During the Treatment Period
Anxiety symptoms were measured using the Comprehensive Psychopathological Rating Scale (CPRS). The CPRS is an 18-item interview-based instrument for assessing depression and anxiety. There are two 10-item subscales, the Montgomery-Asberg Depression Rating Scale (MADRS) and the Brief Scale for Anxiety (BSA). Each subscale ranges from 0 (lowest symptom severity) to 60 (highest symptom severity).
Measured: Day 3 of the treatment period
Anxiety Symptom Ratings Measured Bi-weekly During the Treatment Period
Anxiety symptoms were measured using the Comprehensive Psychopathological Rating Scale (CPRS). The CPRS is an 18-item interview-based instrument for assessing depression and anxiety. There are two 10-item subscales, the Montgomery-Asberg Depression Rating Scale (MADRS) and the Brief Scale for Anxiety (BSA). Each subscale ranges from 0 (lowest symptom severity) to 60 (highest symptom severity).
Measured: Day 7 of the treatment period
Anxiety Symptom Ratings Measured Bi-weekly During the Treatment Period
Anxiety symptoms were measured using the Comprehensive Psychopathological Rating Scale (CPRS). The CPRS is an 18-item interview-based instrument for assessing depression and anxiety. There are two 10-item subscales, the Montgomery-Asberg Depression Rating Scale (MADRS) and the Brief Scale for Anxiety (BSA). Each subscale ranges from 0 (lowest symptom severity) to 60 (highest symptom severity).
Measured: Day 10 of the treatment period
Anxiety Symptom Ratings Measured Bi-weekly During the Treatment Period
Anxiety symptoms were measured using the Comprehensive Psychopathological Rating Scale (CPRS). The CPRS is an 18-item interview-based instrument for assessing depression and anxiety. There are two 10-item subscales, the Montgomery-Asberg Depression Rating Scale (MADRS) and the Brief Scale for Anxiety (BSA). Each subscale ranges from 0 (lowest symptom severity) to 60 (highest symptom severity).
Measured: Day 14 of the treatment period
Anxiety Symptom Ratings Measured Bi-weekly During the Treatment Period
Anxiety symptoms were measured using the Comprehensive Psychopathological Rating Scale (CPRS). The CPRS is an 18-item interview-based instrument for assessing depression and anxiety. There are two 10-item subscales, the Montgomery-Asberg Depression Rating Scale (MADRS) and the Brief Scale for Anxiety (BSA). Each subscale ranges from 0 (lowest symptom severity) to 60 (highest symptom severity).
Measured: Day 17 of the treatment period
Anxiety Symptom Ratings Measured Bi-weekly During the Treatment Period
Anxiety symptoms were measured using the Comprehensive Psychopathological Rating Scale (CPRS). The CPRS is an 18-item interview-based instrument for assessing depression and anxiety. There are two 10-item subscales, the Montgomery-Asberg Depression Rating Scale (MADRS) and the Brief Scale for Anxiety (BSA). Each subscale ranges from 0 (lowest symptom severity) to 60 (highest symptom severity).
Measured: Day 21 of the treatment period
Anxiety Symptom Ratings Measured Bi-weekly During the Treatment Period
Anxiety symptoms were measured using the Comprehensive Psychopathological Rating Scale (CPRS). The CPRS is an 18-item interview-based instrument for assessing depression and anxiety. There are two 10-item subscales, the Montgomery-Asberg Depression Rating Scale (MADRS) and the Brief Scale for Anxiety (BSA). Each subscale ranges from 0 (lowest symptom severity) to 60 (highest symptom severity).
Measured: Day 24 of the treatment period
Anxiety Symptom Ratings Measured Bi-weekly During the Treatment Period
Anxiety symptoms were measured using the Comprehensive Psychopathological Rating Scale (CPRS). The CPRS is an 18-item interview-based instrument for assessing depression and anxiety. There are two 10-item subscales, the Montgomery-Asberg Depression Rating Scale (MADRS) and the Brief Scale for Anxiety (BSA). Each subscale ranges from 0 (lowest symptom severity) to 60 (highest symptom severity).
Measured: Day 28 of the treatment period
Anxiety Symptom Ratings Measured Bi-weekly During the Treatment Period
Anxiety symptoms were measured using the Comprehensive Psychopathological Rating Scale (CPRS). The CPRS is an 18-item interview-based instrument for assessing depression and anxiety. There are two 10-item subscales, the Montgomery-Asberg Depression Rating Scale (MADRS) and the Brief Scale for Anxiety (BSA). Each subscale ranges from 0 (lowest symptom severity) to 60 (highest symptom severity).
Measured: Day 31 of the treatment period
Depression Symptom Ratings Measured Bi-weekly During the Treatment Period
Depression symptoms were measured using the Comprehensive Psychopathological Rating Scale (CPRS). The CPRS is an 18-item interview-based instrument for assessing depression and anxiety. There are two 10-item subscales, the Montgomery-Asberg Depression Rating Scale (MADRS) and the Brief Scale for Anxiety (BSA). Each subscale ranges from 0 (lowest symptom severity) to 60 (highest symptom severity).
Measured: Day 1 of the treatment period
Depression Symptom Ratings Measured Bi-weekly During the Treatment Period
Depression symptoms were measured using the Comprehensive Psychopathological Rating Scale (CPRS). The CPRS is an 18-item interview-based instrument for assessing depression and anxiety. There are two 10-item subscales, the Montgomery-Asberg Depression Rating Scale (MADRS) and the Brief Scale for Anxiety (BSA). Each subscale ranges from 0 (lowest symptom severity) to 60 (highest symptom severity).
Measured: Day 3 of the treatment period
Depression Symptom Ratings Measured Bi-weekly During the Treatment Period
Depression symptoms were measured using the Comprehensive Psychopathological Rating Scale (CPRS). The CPRS is an 18-item interview-based instrument for assessing depression and anxiety. There are two 10-item subscales, the Montgomery-Asberg Depression Rating Scale (MADRS) and the Brief Scale for Anxiety (BSA). Each subscale ranges from 0 (lowest symptom severity) to 60 (highest symptom severity).
Measured: Day 7 of the treatment period
Depression Symptom Ratings Measured Bi-weekly During the Treatment Period
Depression symptoms were measured using the Comprehensive Psychopathological Rating Scale (CPRS). The CPRS is an 18-item interview-based instrument for assessing depression and anxiety. There are two 10-item subscales, the Montgomery-Asberg Depression Rating Scale (MADRS) and the Brief Scale for Anxiety (BSA). Each subscale ranges from 0 (lowest symptom severity) to 60 (highest symptom severity).
Measured: Day 10 of the treatment period
Depression Symptom Ratings Measured Bi-weekly During the Treatment Period
Depression symptoms were measured using the Comprehensive Psychopathological Rating Scale (CPRS). The CPRS is an 18-item interview-based instrument for assessing depression and anxiety. There are two 10-item subscales, the Montgomery-Asberg Depression Rating Scale (MADRS) and the Brief Scale for Anxiety (BSA). Each subscale ranges from 0 (lowest symptom severity) to 60 (highest symptom severity).
Measured: Day 14 of the treatment period
Depression Symptom Ratings Measured Bi-weekly During the Treatment Period
Depression symptoms were measured using the Comprehensive Psychopathological Rating Scale (CPRS). The CPRS is an 18-item interview-based instrument for assessing depression and anxiety. There are two 10-item subscales, the Montgomery-Asberg Depression Rating Scale (MADRS) and the Brief Scale for Anxiety (BSA). Each subscale ranges from 0 (lowest symptom severity) to 60 (highest symptom severity).
Measured: Day 17 of the treatment period
Depression Symptom Ratings Measured Bi-weekly During the Treatment Period
Depression symptoms were measured using the Comprehensive Psychopathological Rating Scale (CPRS). The CPRS is an 18-item interview-based instrument for assessing depression and anxiety. There are two 10-item subscales, the Montgomery-Asberg Depression Rating Scale (MADRS) and the Brief Scale for Anxiety (BSA). Each subscale ranges from 0 (lowest symptom severity) to 60 (highest symptom severity).
Measured: Day 21 of the treatment period
Depression Symptom Ratings Measured Bi-weekly During the Treatment Period
Depression symptoms were measured using the Comprehensive Psychopathological Rating Scale (CPRS). The CPRS is an 18-item interview-based instrument for assessing depression and anxiety. There are two 10-item subscales, the Montgomery-Asberg Depression Rating Scale (MADRS) and the Brief Scale for Anxiety (BSA). Each subscale ranges from 0 (lowest symptom severity) to 60 (highest symptom severity).
Measured: Day 24 of the treatment period
Depression Symptom Ratings Measured Bi-weekly During the Treatment Period
Depression symptoms were measured using the Comprehensive Psychopathological Rating Scale (CPRS). The CPRS is an 18-item interview-based instrument for assessing depression and anxiety. There are two 10-item subscales, the Montgomery-Asberg Depression Rating Scale (MADRS) and the Brief Scale for Anxiety (BSA). Each subscale ranges from 0 (lowest symptom severity) to 60 (highest symptom severity).
Measured: Day 28 of the treatment period
Depression Symptom Ratings Measured Bi-weekly During the Treatment Period
Depression symptoms were measured using the Comprehensive Psychopathological Rating Scale (CPRS). The CPRS is an 18-item interview-based instrument for assessing depression and anxiety. There are two 10-item subscales, the Montgomery-Asberg Depression Rating Scale (MADRS) and the Brief Scale for Anxiety (BSA). Each subscale ranges from 0 (lowest symptom severity) to 60 (highest symptom severity).
Measured: Day 31 of the treatment period
Spontaneous Alcohol Craving Measured Bi-weekly During the Treatment Period
Alcohol craving was measured using the Penn Alcohol Craving Scale (PACS). The PACS is a five-item self-administered instrument for assessing alcohol craving over the course of the past week. The score ranges from 0 (lowest craving value) to 30 (highest craving value).
Measured: Day 1 of the treatment period
Spontaneous Alcohol Craving Measured Bi-weekly During the Treatment Period
Alcohol craving was measured using the Penn Alcohol Craving Scale (PACS). The PACS is a five-item self-administered instrument for assessing alcohol craving over the course of the past week. The score ranges from 0 (lowest craving value) to 30 (highest craving value).
Measured: Day 3 of the treatment period
Spontaneous Alcohol Craving Measured Bi-weekly During the Treatment Period
Alcohol craving was measured using the Penn Alcohol Craving Scale (PACS). The PACS is a five-item self-administered instrument for assessing alcohol craving over the course of the past week. The score ranges from 0 (lowest craving value) to 30 (highest craving value).
Measured: Day 7 of the treatment period
Spontaneous Alcohol Craving Measured Bi-weekly During the Treatment Period
Alcohol craving was measured using the Penn Alcohol Craving Scale (PACS). The PACS is a five-item self-administered instrument for assessing alcohol craving over the course of the past week. The score ranges from 0 (lowest craving value) to 30 (highest craving value).
Measured: Day 10 of the treatment period
Spontaneous Alcohol Craving Measured Bi-weekly During the Treatment Period
Alcohol craving was measured using the Penn Alcohol Craving Scale (PACS). The PACS is a five-item self-administered instrument for assessing alcohol craving over the course of the past week. The score ranges from 0 (lowest craving value) to 30 (highest craving value).
Measured: Day 14 of the treatment period
Spontaneous Alcohol Craving Measured Bi-weekly During the Treatment Period
Alcohol craving was measured using the Penn Alcohol Craving Scale (PACS). The PACS is a five-item self-administered instrument for assessing alcohol craving over the course of the past week. The score ranges from 0 (lowest craving value) to 30 (highest craving value).
Measured: Day 17 of the treatment period
Spontaneous Alcohol Craving Measured Bi-weekly During the Treatment Period
Alcohol craving was measured using the Penn Alcohol Craving Scale (PACS). The PACS is a five-item self-administered instrument for assessing alcohol craving over the course of the past week. The score ranges from 0 (lowest craving value) to 30 (highest craving value).
Measured: Day 21 of the treatment period
Spontaneous Alcohol Craving Measured Bi-weekly During the Treatment Period
Alcohol craving was measured using the Penn Alcohol Craving Scale (PACS). The PACS is a five-item self-administered instrument for assessing alcohol craving over the course of the past week. The score ranges from 0 (lowest craving value) to 30 (highest craving value).
Measured: Day 24 of the treatment period
Spontaneous Alcohol Craving Measured Bi-weekly During the Treatment Period
Alcohol craving was measured using the Penn Alcohol Craving Scale (PACS). The PACS is a five-item self-administered instrument for assessing alcohol craving over the course of the past week. The score ranges from 0 (lowest craving value) to 30 (highest craving value).
Measured: Day 28 of the treatment period
Spontaneous Alcohol Craving Measured Bi-weekly During the Treatment Period
Alcohol craving was measured using the Penn Alcohol Craving Scale (PACS). The PACS is a five-item self-administered instrument for assessing alcohol craving over the course of the past week. The score ranges from 0 (lowest craving value) to 30 (highest craving value).
Measured: Day 31 of the treatment period

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

May 2012Sep 2015

First posted29 Jun 2012 (estimated)
Study startMay 2012
Primary completionSep 2015
Study completionSep 2015

Why it stopped: The study was closed to recruitment due to feasibility problems.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (4)Papers the sponsor has linked to this study.
Other trials for Alcohol DependenceStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 16 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01631630
Sponsor's protocol ID: 120143
Other IDs: 12-AA-0143
Status last verified: Jan 2017
First submitted: 27 Jun 2012
Last updated: 9 Mar 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: No

Publications

Capuron L, Miller AH. Immune system to brain signaling: neuropsychopharmacological implications. Pharmacol Ther. 2011 May;130(2):226-38. doi: 10.1016/j.pharmthera.2011.01.014. Epub 2011 Feb 17.
PubMed 21334376
Crews FT, Zou J, Qin L. Induction of innate immune genes in brain create the neurobiology of addiction. Brain Behav Immun. 2011 Jun;25 Suppl 1(Suppl 1):S4-S12. doi: 10.1016/j.bbi.2011.03.003. Epub 2011 Mar 21.
PubMed 21402143
Dantzer R, Kelley KW. Twenty years of research on cytokine-induced sickness behavior. Brain Behav Immun. 2007 Feb;21(2):153-60. doi: 10.1016/j.bbi.2006.09.006. Epub 2006 Nov 7.
PubMed 17088043
Schwandt ML, Diazgranados N, Umhau JC, Kwako LE, George DT, Heilig M. PPARgamma activation by pioglitazone does not suppress cravings for alcohol, and is associated with a risk of myopathy in treatment seeking alcohol dependent patients: a randomized controlled proof of principle study. Psychopharmacology (Berl). 2020 Aug;237(8):2367-2380. doi: 10.1007/s00213-020-05540-w. Epub 2020 May 22.
PubMed 32445052

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Recruiting
Trial Phase: Syndemic Adapted Medly Uganda
Mental Health
RecruitingPhase 1
Environment and Alcohol: A Pilot Study
Alcohol Use Disorder
RecruitingObservational study
SMART-r: Substance Monitoring and Active Relapse Tracking Repository
Alcoholism, Substance-Related Disorders
Not yet recruiting
A MRT to Optimize a JITAI for Alcohol Craving and Suicide Ideation
Alcohol Use Disorder (AUD), Suicide Ideation
RecruitingPhase 2
Study on Thiamine Supplementation to REduce braiN Injury Associated With Chronic Alcohol Use in Outpatients With Alcohol Use Disorder
Alcohol Use Disorder

All Alcohol Dependence trials

Study at a glance

From the registry record, last updated by the sponsor on 9 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Role of Proinflammatory Signaling in Alcohol Craving
ClinicalTrials.gov ID: NCT01631630
Acronym / sponsor ID: 120143
Conditions: Alcohol Dependence, Alcohol Drinking, Stress, Alcohol-Related Disorders
Keywords: Alcohol, Alcohol Dependence, Alcohol Use, Nicotine Dependence, Nicotine
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: The study was closed to recruitment due to feasibility problems.
Enrolment: 16 participants (actual)
Lead sponsor: National Institute on Alcohol Abuse and Alcoholism (NIAAA)US National Institutes of Health
Study start: May 2012
Primary completion: Sep 2015 (actual)
Study completion: Sep 2015 (actual)
First posted: 29 Jun 2012 (estimated)
Results: Posted 15 Dec 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Background:

Drinking too much alcohol can injure cells in the body. Inflammation is the body s reaction to injured cells. Studies show that inflammation can cause cravings for alcohol. Researchers want to see if pioglitazone, a drug that decreases inflammation, can reduce alcohol craving. If so, it might help develop new ways to help alcoholics with craving.

Objectives:

To see if pioglitazone can reduce alcohol craving.

Eligibility:

Adults between 21 and 65 years of age who are alcoholic and have been drinking within the past month.

Design:

Participants will be screened with a physical exam and medical history. Blood samples will also be collected.
All participants will have inpatient treatment at the National Institutes of Health Clinical Center for the 5 weeks of the study. They will have standard treatment for alcoholism during their inpatient stay.
Half of the people in this study will have pioglitazone. The other half will have a placebo.
Participants will have different studies during their stay. These studies will include the following:
Personalized audio recordings of stressful, alcohol-related, and neutral events to monitor mood
Imaging studies to test alcohol cravings
Questionnaires about mood and alcohol cravings
Lumbar puncture to collect spinal fluid
Inflammation test to see if the study drug can block alcohol cravings
After the end of the 5-week study, all participants will be offered follow-up outpatient care through the Clinical Center, or referral to outside treatment.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 2

Arm	Type	Receives
Pioglitazone	Experimental	Drug: PioglitazoneSubjects received pioglitazone, 15mg/day for 3 days; 30mg day for 3 days; 45mg/day thereafter, for a minimum total of 13 days
Placebo	Placebo comparator	Drug: PlaceboSubjects received placebo on a similar dosing schedule, for a minimum total of 13 days

Who may qualify

Ages: 21 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

Key exclusion criteria (29 listed)

Any medical illness that in the view of the investigators would compromise participation in research, as determined by medical history, physical examination, laboratory tests (see details under Screening measures below), including, but not limited to:
Psychiatric history:
Substance use disorders:
Inability or unwillingness to participate in an fMRI scan, including

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PioglitazoneAlso: ActosPioglitazone is a thiazolidinedione antidiabetic. It works by lowering blood sugar by making the cells of the body more sensitive to the action of insulin.	Drug	Pioglitazone
PlaceboAlso: Sugar PillPlacebo is an inactive tablet design to look exactly like pioglitazone	Drug	Placebo

Primary outcome

Alcohol Craving in Response to the Alcohol Cue Script
Time frame: 15 minutes prior to the beginning of script presentation, which occurred on Day 21, 22, or 23 of the treatment period
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Alcohol Craving in Response to the Alcohol Cue Script
Time frame: 5 minutes after the beginning of script presentation, which occurred on Day 21, 22, or 23 of the treatment period
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Alcohol Craving in Response to the Alcohol Cue Script
Time frame: 15 minutes after the beginning of script presentation, which occurred on Day 21, 22, or 23 of the treatment period
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Alcohol Craving in Response to the Alcohol Cue Script
Time frame: 30 minutes after the beginning of script presentation, which occurred on Day 21, 22, or 23 of the treatment period
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Alcohol Craving in Response to the Alcohol Cue Script
Time frame: 45 minutes after the beginning of script presentation, which occurred on Day 21, 22, or 23 of the treatment period
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Alcohol Craving in Response to the Alcohol Cue Script
Time frame: 60 minutes after the beginning of script presentation, which occurred on Day 21, 22, or 23 of the treatment period
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Alcohol Craving in Response to the Alcohol Cue Script
Time frame: 75 minutes after the beginning of script presentation, which occurred on Day 21, 22, or 23 of the treatment period
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Alcohol Craving in Response to the Alcohol Cue Script
Time frame: 90 minutes after the beginning of script presentation, which occurred on Day 21, 22, or 23 of the treatment period
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Alcohol Craving in Response to the Lipopolysaccharide Challenge
Time frame: 15 minutes prior to the subject receiving an intravenous bolus of lipopolysaccharide, which occurred on Day 25 or Day 32 of the treatment period
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Alcohol Craving in Response to the Lipopolysaccharide Challenge
Time frame: 1 hour after the subject received an intravenous bolus of lipopolysaccharide, which occurred on Day 25 or Day 32 of the treatment period
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Alcohol Craving in Response to the Lipopolysaccharide Challenge
Time frame: 2 hours after the subject received an intravenous bolus of lipopolysaccharide, which occurred on Day 25 or Day 32 of the treatment period
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Alcohol Craving in Response to the Lipopolysaccharide Challenge
Time frame: 3 hours after the subject received an intravenous bolus of lipopolysaccharide, which occurred on Day 25 or Day 32 of the treatment period
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Alcohol Craving in Response to the Lipopolysaccharide Challenge
Time frame: 4 hours after the subject received an intravenous bolus of lipopolysaccharide, which occurred on Day 25 or Day 32 of the treatment period
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Alcohol Craving in Response to the Lipopolysaccharide Challenge
Time frame: 5 hours after the subject received an intravenous bolus of lipopolysaccharide, which occurred on Day 25 or Day 32 of the treatment period
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Alcohol Craving in Response to the Lipopolysaccharide Challenge
Time frame: 6 hours after the subject received an intravenous bolus of lipopolysaccharide, which occurred on Day 25 or Day 32 of the treatment period
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Alcohol Craving in Response to the Stress Script
Time frame: 15 minutes prior to the beginning of script presentation, which occurred on Day 21, 22, or 23 of the treatment period
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Alcohol Craving in Response to the Stress Script
Time frame: 15 minutes after the beginning of script presentation, which occurred on Day 21, 22, or 23 of the treatment period
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Alcohol Craving in Response to the Stress Script
Time frame: 5 minutes after the beginning of script presentation, which occurred on Day 21, 22, or 23 of the treatment period
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Alcohol Craving in Response to the Stress Script
Time frame: 30 minutes after the beginning of script presentation, which occurred on Day 21, 22, or 23 of the treatment period
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Alcohol Craving in Response to the Stress Script
Time frame: 45 minutes after the beginning of script presentation, which occurred on Day 21, 22, or 23 of the treatment period
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Alcohol Craving in Response to the Stress Script
Time frame: 60 minutes after the beginning of script presentation, which occurred on Day 21, 22, or 23 of the treatment period
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Alcohol Craving in Response to the Stress Script
Time frame: 75 minutes after the beginning of script presentation, which occurred on Day 21, 22, or 23 of the treatment period
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Alcohol Craving in Response to the Stress Script
Time frame: 90 minutes after the beginning of script presentation, which occurred on Day 21, 22, or 23 of the treatment period
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).

30 secondary outcomes

Anxiety Symptom Ratings Measured Bi-weekly During the Treatment Period
Time frame: Day 1 of the treatment period
Anxiety Symptom Ratings Measured Bi-weekly During the Treatment Period
Time frame: Day 3 of the treatment period
Anxiety Symptom Ratings Measured Bi-weekly During the Treatment Period
Time frame: Day 7 of the treatment period
Anxiety Symptom Ratings Measured Bi-weekly During the Treatment Period
Time frame: Day 10 of the treatment period
Anxiety Symptom Ratings Measured Bi-weekly During the Treatment Period
Time frame: Day 14 of the treatment period
Anxiety Symptom Ratings Measured Bi-weekly During the Treatment Period
Time frame: Day 17 of the treatment period
Anxiety Symptom Ratings Measured Bi-weekly During the Treatment Period
Time frame: Day 21 of the treatment period
Anxiety Symptom Ratings Measured Bi-weekly During the Treatment Period
Time frame: Day 24 of the treatment period
Anxiety Symptom Ratings Measured Bi-weekly During the Treatment Period
Time frame: Day 28 of the treatment period
Anxiety Symptom Ratings Measured Bi-weekly During the Treatment Period
Time frame: Day 31 of the treatment period
Depression Symptom Ratings Measured Bi-weekly During the Treatment Period
Time frame: Day 1 of the treatment period
Depression Symptom Ratings Measured Bi-weekly During the Treatment Period
Time frame: Day 3 of the treatment period
Depression Symptom Ratings Measured Bi-weekly During the Treatment Period
Time frame: Day 7 of the treatment period
Depression Symptom Ratings Measured Bi-weekly During the Treatment Period
Time frame: Day 10 of the treatment period
Depression Symptom Ratings Measured Bi-weekly During the Treatment Period
Time frame: Day 14 of the treatment period
Depression Symptom Ratings Measured Bi-weekly During the Treatment Period
Time frame: Day 17 of the treatment period
Depression Symptom Ratings Measured Bi-weekly During the Treatment Period
Time frame: Day 21 of the treatment period
Depression Symptom Ratings Measured Bi-weekly During the Treatment Period
Time frame: Day 24 of the treatment period
Depression Symptom Ratings Measured Bi-weekly During the Treatment Period
Time frame: Day 28 of the treatment period
Depression Symptom Ratings Measured Bi-weekly During the Treatment Period
Time frame: Day 31 of the treatment period
Spontaneous Alcohol Craving Measured Bi-weekly During the Treatment Period
Time frame: Day 1 of the treatment period
Spontaneous Alcohol Craving Measured Bi-weekly During the Treatment Period
Time frame: Day 3 of the treatment period
Spontaneous Alcohol Craving Measured Bi-weekly During the Treatment Period
Time frame: Day 7 of the treatment period
Spontaneous Alcohol Craving Measured Bi-weekly During the Treatment Period
Time frame: Day 10 of the treatment period
Spontaneous Alcohol Craving Measured Bi-weekly During the Treatment Period
Time frame: Day 14 of the treatment period
Spontaneous Alcohol Craving Measured Bi-weekly During the Treatment Period
Time frame: Day 17 of the treatment period
Spontaneous Alcohol Craving Measured Bi-weekly During the Treatment Period
Time frame: Day 21 of the treatment period
Spontaneous Alcohol Craving Measured Bi-weekly During the Treatment Period
Time frame: Day 24 of the treatment period
Spontaneous Alcohol Craving Measured Bi-weekly During the Treatment Period
Time frame: Day 28 of the treatment period
Spontaneous Alcohol Craving Measured Bi-weekly During the Treatment Period
Time frame: Day 31 of the treatment period

Results and safety

Results posted to the registry on 15 Dec 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Pioglitazone	8	5
Placebo	8	8

Primary outcome: Alcohol Craving in Response to the Alcohol Cue Script

Time frame: 15 minutes prior to the beginning of script presentation, which occurred on Day 21, 22, or 23 of the treatment period. Least squares mean (Standard Error). Unit: Units on a scale

Measure	Pioglitazone n = 6	Placebo n = 8
Value	13.7505 (2.3136)	8.1871 (1.9853)

Population analysed: The analyses included only those subjects who completed all three script types (neutral, alcohol, stress)

Primary outcome: Alcohol Craving in Response to the Alcohol Cue Script

Time frame: 5 minutes after the beginning of script presentation, which occurred on Day 21, 22, or 23 of the treatment period. Least squares mean (Standard Error). Unit: Units on a scale

Measure	Pioglitazone n = 6	Placebo n = 8
Value	20.5838 (2.3136)	9.6871 (1.9853)

Population analysed: The analyses included only those subjects who completed all three script types (neutral, alcohol, stress)

Primary outcome: Alcohol Craving in Response to the Alcohol Cue Script

Time frame: 15 minutes after the beginning of script presentation, which occurred on Day 21, 22, or 23 of the treatment period. Least squares mean (Standard Error). Unit: Units on a scale

Measure	Pioglitazone n = 6	Placebo n = 8
Value	17.4172 (2.3136)	9.8121 (1.9853)

Population analysed: The analyses included only those subjects who completed all three script types (neutral, alcohol, stress)

Primary outcome: Alcohol Craving in Response to the Alcohol Cue Script

Time frame: 30 minutes after the beginning of script presentation, which occurred on Day 21, 22, or 23 of the treatment period. Least squares mean (Standard Error). Unit: Units on a scale

Measure	Pioglitazone n = 6	Placebo n = 8
Value	19.0838 (2.3136)	10.5621 (1.9853)

Population analysed: The analyses included only those subjects who completed all three script types (neutral, alcohol, stress)

30 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse event data were collected throughout the 31 days of the inpatient stay for each subject. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Pioglitazone	2 of 8 (25%)	8 of 8 (100%)	Not reported
Placebo	0 of 8 (0%)	7 of 8 (87.5%)	Not reported

Limitations and caveats (from the sponsor): This study was terminated early, so the number of subjects analyzed is small.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 21334376Capuron L, Miller AH. Immune system to brain signaling: neuropsychopharmacological implications. Pharmacol Ther. 2011 May;130(2):226-38. doi: 10.1016/j.pharmthera.2011.01.014. Epub 2011 Feb 17.
Background: PubMed 21402143Crews FT, Zou J, Qin L. Induction of innate immune genes in brain create the neurobiology of addiction. Brain Behav Immun. 2011 Jun;25 Suppl 1(Suppl 1):S4-S12. doi: 10.1016/j.bbi.2011.03.003. Epub 2011 Mar 21.
Background: PubMed 17088043Dantzer R, Kelley KW. Twenty years of research on cytokine-induced sickness behavior. Brain Behav Immun. 2007 Feb;21(2):153-60. doi: 10.1016/j.bbi.2006.09.006. Epub 2006 Nov 7.
Derived from this study: PubMed 32445052Schwandt ML, Diazgranados N, Umhau JC, Kwako LE, George DT, Heilig M. PPARgamma activation by pioglitazone does not suppress cravings for alcohol, and is associated with a risk of myopathy in treatment seeking alcohol dependent patients: a randomized controlled proof of principle study. Psychopharmacology (Berl). 2020 Aug;237(8):2367-2380. doi: 10.1007/s00213-020-05540-w. Epub 2020 May 22.
NIH Clinical Center Detailed Web PageLink provided by the sponsor.
Individual participant dataSharing planned: No

Related trials for Alcohol Dependence

Recruiting
Trial Phase: Syndemic Adapted Medly Uganda
Mental Health
RecruitingPhase 1
Environment and Alcohol: A Pilot Study
Alcohol Use Disorder
RecruitingObservational study
SMART-r: Substance Monitoring and Active Relapse Tracking Repository
Alcoholism, Substance-Related Disorders
Not yet recruiting
A MRT to Optimize a JITAI for Alcohol Craving and Suicide Ideation
Alcohol Use Disorder (AUD), Suicide Ideation
RecruitingPhase 2
Study on Thiamine Supplementation to REduce braiN Injury Associated With Chronic Alcohol Use in Outpatients With Alcohol Use Disorder
Alcohol Use Disorder

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Nancy Diazgranados, M.D. principal investigator

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pioglitazone in people with Alcohol Dependence and Alcohol Drinking, run by National Institute on Alcohol Abuse and Alcoholism (NIAAA) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 9 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Dec 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Alcohol Craving in Response to the Alcohol Cue Script (time frame: 15 minutes prior to the beginning of script presentation, which occurred on Day 21, 22, or 23 of the treatment period). The study lists 23 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01631630, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Mar 2017.