Alcohol-Related DisordersPhase 2NCT00106106
Acamprosate to Reduce Symptoms of Alcohol Withdrawal
A Phase 2 study testing NMR-spectroscopy and Oral acamprosate in people with Alcohol-Related Disorders and Alcohol Dependence, run by National Institutes of Health Clinical Center (CC) at 1 site in United States.
Trial summary
This study will examine whether a new drug called acamprosate can be helpful for alcohol withdrawal, a result of drinking high amounts of alcohol for long periods of time. Alcohol withdrawal can cause various symptoms, including nausea or vomiting, anxiety or depression, tremor, high blood pressure, and others. Read more about this study
- Who is it for?
- Ages 21 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Alcohol-Related Disorders, Alcohol Dependence, Alcoholism
- What is being tested?
- NMR-spectroscopy and Oral acamprosate
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 56 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2005to Jul 2010
- 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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Alcohol dependence according to DSM-IV, based on the alcohol dependence module of the SCID I-interview, and alcohol withdrawal, based on either of:
- Clinically manifest significant alcohol withdrawal symptoms, with or without detectable blood alcohol concentrations.
- In absence of the above, current intoxication above 0.1 g/dl BAC, self-reported history of continuous alcohol use > 1 month, and self-reported previous episodes of significantly distressful alcohol withdrawal symptoms, whether treated or not.
- Age 21 - 65; in younger subjects, maturation processes of the central nervous system are still ongoing; while in older subjects, degenerative changes may confound the measures studied.
- Smoking status: this will be noted and evaluated using the Fagerstrom inventory, so that its potential contribution to group differences can be assessed. This variable will not otherwise affect inclusion / exclusion.
- Subjects will be eligible for inclusion if they are aged 21-65. They will be as closely as possible matched to the patient population with regard to gender and age.
Who cannot join
- Current or prior history of any disease, including cardiovascular, respiratory, gastrointestinal, hepatic, renal, endocrine, or reproductive disorders, or a positive hepatitis or HIV test at screening.
- Current Axis-I psychiatric illness.
- Current or prior history of any alcohol or drug dependence, as well as non-drinkers (alcohol-naive individuals or current abstainers).
- Positive result on urine screen for illicit drugs.
- Nursing, pregnancy or intention to become pregnant for women. Female participants will undergo a urine beta-hCG test to ensure they are not pregnant.
- Pregnancy (negative test required) or ongoing breastfeeding.
Show all 15Show fewer
- Use of prescription or OTC medications know to interact with alcohol within 2 weeks of the study. These include, but may not be limited to: isosorbide, nitroglycerine, benzodiazepines, warfarin, anti-depressants such as amitriptyline, clomipramine and nefazodone, anti-diabetes medications such as glyburide, metformin and tolbutamide, H2-antagonists for heartburn such as cimetidine and ranitidine, muscle relaxants, anti-epileptics including phenytoin and Phenobarbital codeine, and narcotics including darvocet, percocet and hydrocodone. Drugs known to inhibit or induce enzymes that metabolize alcohol should not be used for 4 weeks prior to the study. These include chlorzoxazone, isoniazid, metronidazole and disulfiram. Cough-and-cold preparations which contain anti-histamines, pain medicines and anti-inflammatories such as aspirin, ibuprofen, acetaminophen, celecoxib and naproxen, should be withheld for at least a 72 hours prior to each study session.
- Self-reported history of flushing upon intake of alcohol.
- Inability to undergo an MR scan, due to presence of ferromagnetic objects in their bodies which could cause adverse effects in the MRI scanner, pronounced anxiety provoked by enclosed spaces, or other reasons.
- History of any substance use disorder.
- Average weekly consumption over last 4 weeks, assessed with Time-Line Follow-Back, exceeding 210g pure alcohol / week, or consumption of more than 60g pure alcohol on any single occasion within last 3 days
- Any history of a psychotic disorder or a history of any other psychiatric diagnosis within the last 12 months
- Any prescription medication within the last 2 months
- Pregnant (negative pregnancy test required) or breastfeeding
- Inability to undergo an MR scan, due to presence of ferromagnetic objects in their bodies which could cause adverse effects in the MRI scanner, pronounced anxiety provoked by enclosed spaces, or other reason
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Acamprosate for Central Nervous System Hyperexcitability and Neuroadaptation in Alcohol Withdrawal
This study will examine whether a new drug called acamprosate can be helpful for alcohol withdrawal, a result of drinking high amounts of alcohol for long periods of time. Alcohol withdrawal can cause various symptoms, including nausea or vomiting, anxiety or depression, tremor, high blood pressure, and others. During withdrawal, brain chemicals called neurotransmitters change, with some rising to abnormally high levels. These changes may contribute to alcohol craving, drinking relapse and impaired mental performance. This study will see if taking acamprosate for 4 weeks can lower the levels of neurotransmitters, such as glutamate, lessen withdrawal symptoms and decrease alcohol craving and brain damage associated with withdrawal.
Healthy normal volunteers and alcohol-dependent patients between 21 and 65 years of age may be eligible for this study.
Read more
Participants are admitted to the hospital for 28 days. They receive standard inpatient care for alcohol detoxification, including a medical history and physical examination, neurological evaluation, laboratory tests, nursing, nutrition, discharge planning and referrals for treatment of concomitant conditions, if needed. In addition, they are randomly assigned to take either two acamprosate or two placebo pills three times a day for 28 days and undergo the following tests and procedures:
- Days 1-28: Drug treatment. Patients take acamprosate or placebo daily. Patients with severe withdrawal symptoms may also receive diazepam (Valium). Throughout their hospitalization, patients fill out questionnaires about their emotional state and personality and are interviewed by staff about their mental health, use of alcohol, cigarettes, and illicit drugs, employment, support systems and family and social relationships, and their legal status.
- Days 2 and 3: Blood tests. Blood is tested for levels of the stress hormones cortisol and ACTH, which are released to excess during alcohol withdrawal. For this test, a heparin lock (thin, flexible plastic tube with a rubber stopper on the end) is placed in an arm vein for blood collections each day at 6 AM, 12 noon, 6 PM and 12 midnight. Patients rest in bed for 30 minutes before each collection.
- Day 4: Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). These procedures are done at the same time. They use a strong magnetic field and radio waves to show structural and chemical changes in the brain. The patient lies on a table in a space enclosed by a metal cylinder (the scanner) for about 20 to 30 minutes during the test.
- Day 5: Lumbar puncture (spinal tap). A local anesthetic is given to numb the area for the procedure. Then, a needle is inserted in the space between the bones in the lower back where the cerebrospinal fluid circulates below the spinal cord. A small amount of fluid is collected through the needle.
- Days 5 and 6: Dexamethasone-corticotropin releasing factor (CRF) test. This test measures the effect of alcohol withdrawal on ACTH and cortisol. The patient takes a standard dose of the steroid dexamethasone at 11 PM on day 5. At noon the next day, they are given lunch and then stay in bed and rest. A plastic tube is put in an arm vein. A salt water solution is slowly infused through the catheter and a blood sample is withdrawn through it. At 3 p.m., the patient is given 100 micrograms of the hormone CRF. Repeated blood samples are obtained to measure ACTH and cortisol.
- Days 23-27: All of the tests done on days 2-6 are repeated, except the MRI. MRS is repeated to measure neurotransmitters.
Read the detailed description
Objective: Clinical as well as preclinical studies indicate that the process of developing alcohol dependence recruits a progressively aggravated hyperglutamatergic state, which in turn is a key signal for emotional dysregulations leading to craving and relapse, as well as neurotoxicity leading to cognitive impairment and loss of grey matter in alcoholic patients. Acamprosate has recently been approved for relapse prevention in sober alcoholics, an effect mediated through largely unknown mechanisms. Preclinical data indicate, however, that it might primarily be useful for targeting the hyperglutamatergic state that develops during recurring withdrawal episodes, halting the process described above. If so, acamprosate might be of value as a withdrawal treatment to prevent the progression of alcohol dependence. The aim of the present protocol is to evaluate, in a randomized controlled trial, the effects of acamprosate during withdrawal and the early post-withdrawal phase. The primary outcome variable will be central glutamate/glutamine concentration as determined by MR spectroscopy. A number of exploratory biological and clinical measures will in addition be obtained and used for secondary analyses as specified below.
Study Population: We will study patients age 21 - 65, without gross impairment of judgment or complicated psychiatric or other morbidity, going into withdrawal or with a high probability of doing so, will be admitted as inpatients to the NIAAA CC-unit. A group of healthy volunteers who do not receive study medication will be examined separately in order to confirm that a hyperglutamatergic state is present in the patients during withdrawal.
Design: All patients will receive standard care for alcohol detoxification. In addition, half of them will be randomized in a blinded fashion to oral acamprosate, two 333 mg tablets taken 3 times daily or corresponding placebo. Validated rating scales (CIWA-Ar, CPRS-SA) will be used to assess intensity of withdrawal and psychopathology. If severity of withdrawal exceeds a predefined criterion, standard diazepam treatment will be added to study medication. The accrual target is based on a primary analysis sample of patients who will not require diazepam medication, which is a potential confound. A secondary analysis will be carried out on the complete sample, analyzing the requirement for/amount of diazepam supplement as a secondary outcome variable.
Outcome Measures: A battery of tests will be obtained during the 1st and 3rd week of inpatient treatment. These will include NMR-spectroscopy to quantify central levels of excitatory and inhibitory amino acids (primary outcome variable: GluX concentration); lumbar puncture to obtain CSF for analysis of neurotransmitter/neurohormone metabolites and synaptic proteins. Repeated 4 x daily blood collection for analysis of serum cortisol and ACTH will be obtained to assess spontaneous activity and circadian variation of the HPA-axis, and the combined dexamethasone - CRH test will be carried out to dynamically probe this system, and gauge its sensitivity for feedback inhibition.
- Being tested
- NMR-spectroscopy, Oral acamprosate
- Keywords
- Alcoholism, Acamprosate, Withdrawal, Glutamate, Magnetic Resonance Spectroscopy, Alcohol Dependence, Healthy Volunteer, HV
- Medical subject headings
- Alcohol-Related Disorders, Alcoholism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NMR-spectroscopyProcedure or surgery
Also called Magnetic Resonance Spectroscopy, MRS
Scans were performed on a 3T scanner using the echo-time-averaged PRESS sequence previously published to detect glutamate's resonance line at 2.35 ppm and average out the interferences from glutamine, NAA and the macromolecules.
Oral acamprosateDrug
Also called Campral
For subjects randomized to active treatment, the first 3 acamprosate doses were 1332 mg every 8 hours in an attempt to more rapidly achieve active plasma concentrations, followed by 666 mg acamprosate every 8 hours for the remainder of the study.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | For subjects randomized to placebo control, placebo doses were given every 8 hours. Receives: Procedure: NMR-spectroscopy |
| Acamprosate | Experimental | For subjects randomized to active treatment, the first 3 acamprosate doses were 1332 mg every 8 hours in an attempt to more rapidly achieve active plasma concentrations, followed by 666 mg acamprosate every 8 hours for the remainder of the study. Receives: Procedure: NMR-spectroscopy; Drug: Oral acamprosate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ratio of Glutamate to Creatine in the Anterior Cingulate of the Brain, Measured on Day 4
The ratio of glutamate to creatine was determined using magnetic resonance spectroscopy (MRS), a technique that complements magnetic resonance imaging (MRI). MRS is used to determine the concentration of brain metabolites, such as glutamate, in brain tissue. MRS utilizes a magnetic field to look at magnetic nuclei, which absorb and re-emit electromagnetic energy in the presence of the magnetic field. By looking at the peaks in the resultant spectra the structure and concentration of metabolites can be determined.
Measured: Day 4
Ratio of Glutamate to Creatine in the Anterior Cingulate of the Brain, Measured on Day 25
The ratio of glutamate to creatine was determined using magnetic resonance spectroscopy (MRS), a technique that complements magnetic resonance imaging (MRI). MRS is used to determine the concentration of brain metabolites, such as glutamate, in brain tissue. MRS utilizes a magnetic field to look at magnetic nuclei, which absorb and re-emit electromagnetic energy in the presence of the magnetic field. By looking at the peaks in the resultant spectra the structure and concentration of metabolites can be determined.
Measured: Day 25
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Mar 2005 (estimated)
- Study startMar 2005
- Primary completionJul 2010
- Study completionJul 2010
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 (6)Papers the sponsor has linked to this study.
- Other trials for Alcohol-Related DisordersStudies 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
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institutes of Health Clinical Center (CC)
- Sponsor type
- US National Institutes of Health
- Collaborators
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Responsible party
- Principal investigator, Markus Heilig, National Institute on Alcohol Abuse and Alcoholism (NIAAA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00106106
- Sponsor's protocol ID
- 050120
- Other IDs
- 05-AA-0120
- Status last verified
- Jan 2012
- First submitted
- 19 Mar 2005
- Last updated
- 12 Jan 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Daeppen JB, Gache P, Landry U, Sekera E, Schweizer V, Gloor S, Yersin B. Symptom-triggered vs fixed-schedule doses of benzodiazepine for alcohol withdrawal: a randomized treatment trial. Arch Intern Med. 2002 May 27;162(10):1117-21. doi: 10.1001/archinte.162.10.1117.
PubMed 12020181Liskow BI, Goodwin DW. Pharmacological treatment of alcohol intoxication, withdrawal and dependence: a critical review. J Stud Alcohol. 1987 Jul;48(4):356-70. doi: 10.15288/jsa.1987.48.356.
PubMed 2956463Mayo-Smith MF. Pharmacological management of alcohol withdrawal. A meta-analysis and evidence-based practice guideline. American Society of Addiction Medicine Working Group on Pharmacological Management of Alcohol Withdrawal. JAMA. 1997 Jul 9;278(2):144-51. doi: 10.1001/jama.278.2.144.
PubMed 9214531Vatsalya V, Cave MC, Kumar R, Srivastava S, Khanal S, Jenson AB, Schwandt ML, Barve SS, Ramchandani VA, McClain CJ. Alterations in Serum Zinc and Polyunsaturated Fatty Acid Concentrations in Treatment-Naive HIV-Diagnosed Alcohol-Dependent Subjects with Liver Injury. AIDS Res Hum Retroviruses. 2019 Jan;35(1):92-99. doi: 10.1089/AID.2018.0124. Epub 2018 Dec 11.
PubMed 30280905Vatsalya V, Kong M, Cave MC, Liu N, Schwandt ML, George DT, Ramchandani VA, McClain CJ. Association of serum zinc with markers of liver injury in very heavy drinking alcohol-dependent patients. J Nutr Biochem. 2018 Sep;59:49-55. doi: 10.1016/j.jnutbio.2018.05.003. Epub 2018 May 12.
PubMed 29960116Umhau JC, Momenan R, Schwandt ML, Singley E, Lifshitz M, Doty L, Adams LJ, Vengeliene V, Spanagel R, Zhang Y, Shen J, George DT, Hommer D, Heilig M. Effect of acamprosate on magnetic resonance spectroscopy measures of central glutamate in detoxified alcohol-dependent individuals: a randomized controlled experimental medicine study. Arch Gen Psychiatry. 2010 Oct;67(10):1069-77. doi: 10.1001/archgenpsychiatry.2010.125.
PubMed 20921123
Study at a glance
From the registry record, last updated by the sponsor on 12 Jan 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Acamprosate for Central Nervous System Hyperexcitability and Neuroadaptation in Alcohol Withdrawal
- ClinicalTrials.gov ID
- NCT00106106
- Acronym / sponsor ID
- 050120
- Keywords
- Alcoholism, Acamprosate, Withdrawal, Glutamate, Magnetic Resonance Spectroscopy, Alcohol Dependence, Healthy Volunteer, HV
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- National Institutes of Health Clinical Center (CC)US National Institutes of Health
- Collaborators
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Study start
- Mar 2005
- Primary completion
- Jul 2010 (actual)
- Study completion
- Jul 2010 (actual)
- First posted
- 21 Mar 2005 (estimated)
- Results
- Posted 5 Jan 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will examine whether a new drug called acamprosate can be helpful for alcohol withdrawal, a result of drinking high amounts of alcohol for long periods of time. Alcohol withdrawal can cause various symptoms, including nausea or vomiting, anxiety or depression, tremor, high blood pressure, and others. During withdrawal, brain chemicals called neurotransmitters change, with some rising to abnormally high levels. These changes may contribute to alcohol craving, drinking relapse and impaired mental performance. This study will see if taking acamprosate for 4 weeks can lower the levels of neurotransmitters, such as glutamate, lessen withdrawal symptoms and decrease alcohol craving and brain damage associated with withdrawal.
Healthy normal volunteers and alcohol-dependent patients between 21 and 65 years of age may be eligible for this study.
Participants are admitted to the hospital for 28 days. They receive standard inpatient care for alcohol detoxification, including a medical history and physical examination, neurological evaluation, laboratory tests, nursing, nutrition, discharge planning and referrals for treatment of concomitant conditions, if needed. In addition, they are randomly assigned to take either two acamprosate or two placebo pills three times a day for 28 days and undergo the following tests and procedures:
- Days 1-28: Drug treatment. Patients take acamprosate or placebo daily. Patients with severe withdrawal symptoms may also receive diazepam (Valium). Throughout their hospitalization, patients fill out questionnaires about their emotional state and personality and are interviewed by staff about their mental health, use of alcohol, cigarettes, and illicit drugs, employment, support systems and family and social relationships, and their legal status.
- Days 2 and 3: Blood tests. Blood is tested for levels of the stress hormones cortisol and ACTH, which are released to excess during alcohol withdrawal. For this test, a heparin lock (thin, flexible plastic tube with a rubber stopper on the end) is placed in an arm vein for blood collections each day at 6 AM, 12 noon, 6 PM and 12 midnight. Patients rest in bed for 30 minutes before each collection.
- Day 4: Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). These procedures are done at the same time. They use a strong magnetic field and radio waves to show structural and chemical changes in the brain. The patient lies on a table in a space enclosed by a metal cylinder (the scanner) for about 20 to 30 minutes during the test.
- Day 5: Lumbar puncture (spinal tap). A local anesthetic is given to numb the area for the procedure. Then, a needle is inserted in the space between the bones in the lower back where the cerebrospinal fluid circulates below the spinal cord. A small amount of fluid is collected through the needle.
- Days 5 and 6: Dexamethasone-corticotropin releasing factor (CRF) test. This test measures the effect of alcohol withdrawal on ACTH and cortisol. The patient takes a standard dose of the steroid dexamethasone at 11 PM on day 5. At noon the next day, they are given lunch and then stay in bed and rest. A plastic tube is put in an arm vein. A salt water solution is slowly infused through the catheter and a blood sample is withdrawn through it. At 3 p.m., the patient is given 100 micrograms of the hormone CRF. Repeated blood samples are obtained to measure ACTH and cortisol.
- Days 23-27: All of the tests done on days 2-6 are repeated, except the MRI. MRS is repeated to measure neurotransmitters.
Detailed description
Objective: Clinical as well as preclinical studies indicate that the process of developing alcohol dependence recruits a progressively aggravated hyperglutamatergic state, which in turn is a key signal for emotional dysregulations leading to craving and relapse, as well as neurotoxicity leading to cognitive impairment and loss of grey matter in alcoholic patients. Acamprosate has recently been approved for relapse prevention in sober alcoholics, an effect mediated through largely unknown mechanisms. Preclinical data indicate, however, that it might primarily be useful for targeting the hyperglutamatergic state that develops during recurring withdrawal episodes, halting the process described above. If so, acamprosate might be of value as a withdrawal treatment to prevent the progression of alcohol dependence. The aim of the present protocol is to evaluate, in a randomized controlled trial, the effects of acamprosate during withdrawal and the early post-withdrawal phase. The primary outcome variable will be central glutamate/glutamine concentration as determined by MR spectroscopy. A number of exploratory biological and clinical measures will in addition be obtained and used for secondary analyses as specified below.
Study Population: We will study patients age 21 - 65, without gross impairment of judgment or complicated psychiatric or other morbidity, going into withdrawal or with a high probability of doing so, will be admitted as inpatients to the NIAAA CC-unit. A group of healthy volunteers who do not receive study medication will be examined separately in order to confirm that a hyperglutamatergic state is present in the patients during withdrawal.
Design: All patients will receive standard care for alcohol detoxification. In addition, half of them will be randomized in a blinded fashion to oral acamprosate, two 333 mg tablets taken 3 times daily or corresponding placebo. Validated rating scales (CIWA-Ar, CPRS-SA) will be used to assess intensity of withdrawal and psychopathology. If severity of withdrawal exceeds a predefined criterion, standard diazepam treatment will be added to study medication. The accrual target is based on a primary analysis sample of patients who will not require diazepam medication, which is a potential confound. A secondary analysis will be carried out on the complete sample, analyzing the requirement for/amount of diazepam supplement as a secondary outcome variable.
Outcome Measures: A battery of tests will be obtained during the 1st and 3rd week of inpatient treatment. These will include NMR-spectroscopy to quantify central levels of excitatory and inhibitory amino acids (primary outcome variable: GluX concentration); lumbar puncture to obtain CSF for analysis of neurotransmitter/neurohormone metabolites and synaptic proteins. Repeated 4 x daily blood collection for analysis of serum cortisol and ACTH will be obtained to assess spontaneous activity and circadian variation of the HPA-axis, and the combined dexamethasone - CRH test will be carried out to dynamically probe this system, and gauge its sensitivity for feedback inhibition.
Study design
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Procedure: NMR-spectroscopyFor subjects randomized to placebo control, placebo doses were given every 8 hours. |
| Acamprosate | Experimental | Procedure: NMR-spectroscopy, Drug: Oral acamprosateFor subjects randomized to active treatment, the first 3 acamprosate doses were 1332 mg every 8 hours in an attempt to more rapidly achieve active plasma concentrations, followed by 666 mg acamprosate every 8 hours for the remainder of the study. |
Who may qualify
- Ages
- 21 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Clinically manifest significant alcohol withdrawal symptoms, with or without detectable blood alcohol concentrations.
- In absence of the above, current intoxication above 0.1 g/dl BAC, self-reported history of continuous alcohol use > 1 month, and self-reported previous episodes of significantly distressful alcohol withdrawal symptoms, whether treated or not.
- Subjects will be eligible for inclusion if they are aged 21-65. They will be as closely as possible matched to the patient population with regard to gender and age.
Key exclusion criteria (15 listed)
- Current or prior history of any disease, including cardiovascular, respiratory, gastrointestinal, hepatic, renal, endocrine, or reproductive disorders, or a positive hepatitis or HIV test at screening.
- Current Axis-I psychiatric illness.
- Current or prior history of any alcohol or drug dependence, as well as non-drinkers (alcohol-naive individuals or current abstainers).
- Positive result on urine screen for illicit drugs.
- Nursing, pregnancy or intention to become pregnant for women. Female participants will undergo a urine beta-hCG test to ensure they are not pregnant.
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 |
|---|---|---|
| NMR-spectroscopyAlso: Magnetic Resonance Spectroscopy, MRSScans were performed on a 3T scanner using the echo-time-averaged PRESS sequence previously published to detect glutamate's resonance line at 2.35 ppm and average out the interferences from glutamine, NAA and the macromolecules. | Procedure or surgery | Acamprosate, Placebo |
| Oral acamprosateAlso: CampralFor subjects randomized to active treatment, the first 3 acamprosate doses were 1332 mg every 8 hours in an attempt to more rapidly achieve active plasma concentrations, followed by 666 mg acamprosate every 8 hours for the remainder of the study. | Drug | Acamprosate |
Primary outcome
Ratio of Glutamate to Creatine in the Anterior Cingulate of the Brain, Measured on Day 4
Time frame: Day 4
The ratio of glutamate to creatine was determined using magnetic resonance spectroscopy (MRS), a technique that complements magnetic resonance imaging (MRI). MRS is used to determine the concentration of brain metabolites, such as glutamate, in brain tissue. MRS utilizes a magnetic field to look at magnetic nuclei, which absorb and re-emit electromagnetic energy in the presence of the magnetic field. By looking at the peaks in the resultant spectra the structure and concentration of metabolites can be determined.
Ratio of Glutamate to Creatine in the Anterior Cingulate of the Brain, Measured on Day 25
Time frame: Day 25
The ratio of glutamate to creatine was determined using magnetic resonance spectroscopy (MRS), a technique that complements magnetic resonance imaging (MRI). MRS is used to determine the concentration of brain metabolites, such as glutamate, in brain tissue. MRS utilizes a magnetic field to look at magnetic nuclei, which absorb and re-emit electromagnetic energy in the presence of the magnetic field. By looking at the peaks in the resultant spectra the structure and concentration of metabolites can be determined.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jan 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 12020181Daeppen JB, Gache P, Landry U, Sekera E, Schweizer V, Gloor S, Yersin B. Symptom-triggered vs fixed-schedule doses of benzodiazepine for alcohol withdrawal: a randomized treatment trial. Arch Intern Med. 2002 May 27;162(10):1117-21. doi: 10.1001/archinte.162.10.1117.
- Background: PubMed 2956463Liskow BI, Goodwin DW. Pharmacological treatment of alcohol intoxication, withdrawal and dependence: a critical review. J Stud Alcohol. 1987 Jul;48(4):356-70. doi: 10.15288/jsa.1987.48.356.
- Background: PubMed 9214531Mayo-Smith MF. Pharmacological management of alcohol withdrawal. A meta-analysis and evidence-based practice guideline. American Society of Addiction Medicine Working Group on Pharmacological Management of Alcohol Withdrawal. JAMA. 1997 Jul 9;278(2):144-51. doi: 10.1001/jama.278.2.144.
- Derived from this study: PubMed 30280905Vatsalya V, Cave MC, Kumar R, Srivastava S, Khanal S, Jenson AB, Schwandt ML, Barve SS, Ramchandani VA, McClain CJ. Alterations in Serum Zinc and Polyunsaturated Fatty Acid Concentrations in Treatment-Naive HIV-Diagnosed Alcohol-Dependent Subjects with Liver Injury. AIDS Res Hum Retroviruses. 2019 Jan;35(1):92-99. doi: 10.1089/AID.2018.0124. Epub 2018 Dec 11.
- Derived from this study: PubMed 29960116Vatsalya V, Kong M, Cave MC, Liu N, Schwandt ML, George DT, Ramchandani VA, McClain CJ. Association of serum zinc with markers of liver injury in very heavy drinking alcohol-dependent patients. J Nutr Biochem. 2018 Sep;59:49-55. doi: 10.1016/j.jnutbio.2018.05.003. Epub 2018 May 12.
- Derived from this study: PubMed 20921123Umhau JC, Momenan R, Schwandt ML, Singley E, Lifshitz M, Doty L, Adams LJ, Vengeliene V, Spanagel R, Zhang Y, Shen J, George DT, Hommer D, Heilig M. Effect of acamprosate on magnetic resonance spectroscopy measures of central glutamate in detoxified alcohol-dependent individuals: a randomized controlled experimental medicine study. Arch Gen Psychiatry. 2010 Oct;67(10):1069-77. doi: 10.1001/archgenpsychiatry.2010.125.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 NMR-spectroscopy and Oral acamprosate in people with Alcohol-Related Disorders and Alcohol Dependence, run by National Institutes of Health Clinical Center (CC) 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 15 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: finished, as of the sponsor's last update on 12 Jan 2012. 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 5 Jan 2012). 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?
Ratio of Glutamate to Creatine in the Anterior Cingulate of the Brain, Measured on Day 4 (time frame: Day 4). The study lists 2 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 NCT00106106, which also lists 6 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 12 Jan 2012.