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Alcohol Use Disorder With InsomniaPhase 4NCT04581603

CBT-I Augmentation of Medication for Drinking in AUD

A Phase 4 study testing Cognitive Behavioral Therapy for Insomnia and Sleep Hygiene Education in people with Alcohol Use Disorder With Insomnia, run by VA Office of Research and Development at 2 sites in United States.

Terminated

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

Official record
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Trial summary

Alcohol Use Disorder (AUD) and insomnia are more prevalent in Veterans than in the general community. Furthermore, insomnia is comorbid in 36-91% of individuals with AUD and jeopardizes recovery by increasing their risk for relapse and complicating their clinical profile. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Alcohol Use Disorder With Insomnia
What is being tested?
Cognitive Behavioral Therapy for Insomnia and Sleep Hygiene Education
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
82 participants
Where
2 sitesUnited States
Study dates
15 Jun 2022to 20 Jan 2025
Phase
Phase 4
Are there results?
None posted in the registry

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 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male and female Veterans between the ages of 18 and 70 years.
  • A past-year DSM-5 diagnosis of moderate to severe AUD (i.e., meeting 4 of the 11 DSM-5 criteria for AUD)
  • Actively drinking alcohol within the past month ( 2 heavy drinking days, defined as 4 drinks/day for women and 5 drinks/day for men).
  • Self-reported insomnia of moderate or severe intensity (i.e., an Insomnia Severity Index total score 15).
  • Subject has expressed a desire to stop or reduce drinking.
  • Capacity to comprehend and give informed consent.
  • Women of child-bearing potential (i.e., who have not had a hysterectomy, bilateral oophorectomy, tubal ligation or is less than two years postmenopausal), must be non-lactating, practicing a reliable method of birth control, and have a negative urine pregnancy test prior to initiation of treatment.

Who cannot join

  • General
  • A current, clinically significant physical disease or abnormality based on history, physical examination, or routine laboratory evaluation.
  • Current serious psychiatric illness (i.e., schizophrenia, bipolar disorder, severe or psychotic major depression, eating disorder, or imminent suicide or violence risk).
  • DSM-5 criteria for any other substance use disorder other than alcohol, nicotine, cannabis use disorder, or mild stimulant (cocaine) use disorder.
  • Untreated subjects with a diagnosis of moderate-severe obstructive sleep apnea with a total Apnea Hypopnea Index (AHI-T) of 15 events/hour of sleep.
  • Recent (within the 10 days prior to the baseline visit) exposure to licit or illicit opioids as defined by self-report or a positive urine drug screen. Individuals on a prescription low-dose opioid medication for chronic pain are eligible for treatment with TOP only, and positive urine drug screen(s) will not be exclusionary in this case.
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  • Patient also agrees not to initiate CBT for alcohol use disorder during the trial or will be discontinued.
  • Completed a full course of CBT-I within the past year.
  • Specific to Naltrexone treatment
  • A history of hypersensitivity to naltrexone.
  • A transaminase elevation >300% of normal.
  • Active treatment with opioid medications.
  • Specific to Topiramate treatment
  • A history of hypersensitivity to TOP.
  • A history of nephrolithiasis.
  • A history of narrow angle glaucoma.
  • Current treatment with medications considered a high risk for adverse reactions for TOP treatment, such as carbonic anhydrase inhibitors.

Trial locations and contacts

2 sites in 1 country.

United States2 sites
  • Coatesville VA Medical Center, Coatesville, PA

    Coatesville, Pennsylvania, 19320

  • Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA

    Philadelphia, Pennsylvania, 19104-4551

Other trials in United States

About this study

Official title: Cognitive Behavioral Therapy (CBT-I) Augmentation of Topiramate in Promoting Abstinence in Alcohol Use Disorder (AUD)

Alcohol Use Disorder (AUD) and insomnia are more prevalent in Veterans than in the general community. Furthermore, insomnia is comorbid in 36-91% of individuals with AUD and jeopardizes recovery by increasing their risk for relapse and complicating their clinical profile. The VA/DoD guidelines recommend four medications for the treatment of AUD by promoting abstinence and a reduction in drinking. Two of these medications (MED) used commonly are naltrexone and topiramate but they do not improve sleep continuity or insomnia. The recommended treatment for insomnia is Cognitive Behavioral Therapy for Insomnia (CBT-I), and it has shown efficacy in improving insomnia but with minimal benefit in improving abstinence. However, these studies have involved subjects in early or sustained remission. The proposed study will evaluate whether augmenting MED with CBT-I, after reducing drinking or achieving abstinence, bolsters recovery in AUD, by decreasing insomnia and improving abstinence. If this strategy shows good clinical results and the findings are replicated in a multi-center trial then the combination of MED with CBT-I should be considered a standard component of the initial management of AUD with insomnia.

Read the detailed description

Alcohol Use Disorder (AUD) and insomnia are both more prevalent among Veterans than in the general population. While insomnia is 3-9 times more prevalent in AUD than in the general population, patients with comorbid AUD and insomnia suffer from higher severity of AUD with increased alcohol craving, reduced quality of life, impaired interpersonal functioning, higher risks for suicidal behavior and relapse during early abstinence. There are limited options to treat drinking behavior and insomnia due to side effect profile (disulfiram). Medications commonly used to treat pathological drinking and promote abstinence include Naltrexone and Topiramate. However, these medications do not improve insomnia. Furthermore, hypnotic medication treatments with trazodone, gabapentin, and ramelteon have shown variable impact for sleep disturbance and abstinence. By contrast, all four studies evaluating Cognitive Behavioral Therapy for Insomnia (CBT-I) have shown a large magnitude of effect for treating insomnia but with minimal to no effect on abstinence. Thus, combining MED and CBT-I will improve their insomnia and bolster their recovery. This combination treatment will be the first personalized intervention in treating Veterans with AUD and comorbid insomnia.

A sample of treatment-seeking Veterans with AUD (N=82) will be initially treated with a medication for drinking (MED), that will be either TOP 200 mg a day for six weeks, naltrexone 50 mg daily (and up to 100 mg daily), depot-naltrexone 380 mg injections every 4 weeks, or a combination of TOP + NTX. They will stabilized on the MED over 6 weeks and then randomized to receive either CBT-I (N=41) or Sleep Hygiene Education (SHE, a behavioral placebo intervention) (N=41) weekly for the next eight weeks. The investigators will conduct CBT-I following the standard protocol using 30-minute sessions to deliver its components (Sleep Restriction, Stimulus Control, Sleep Hygiene and Cognitive Therapy). A post-intervention visit will be conducted eight weeks after the end of the intervention phase. The primary outcome measure will be the the insomnia severity (as assessed using the Insomnia Severity Index). The secondary outcome measure will include the Percent Days Abstinent (as computed from the Time Line Follow Back interview). The investigators will also track other aspects of alcohol use, sleep and daily functioning using TLFB, PACS, sleep diaries, BDI, and the STAI to test whether successful treatment of drinking and insomnia will be associated with better clinical outcomes in AUD. It is hypothesized that in Veterans with AUD, the combination of MED+CBT-I, as compared to MED+SHE group, will lead to superior sleep-related outcomes along with pre-post treatment effect sizes comparable to the meta-analytic norms. On an exploratory basis, the MED + CBT-I arm will have a relatively higher percentage of days abstinent from alcohol and the improvement in insomnia and abstinence from drinking will show durability eight weeks after end of behavioral sleep treatment. If these hypotheses are supported, the findings will need to be validated in a larger multi-center trial. If validated, the findings would support: 1) including insomnia treatment as a standard component of the initial protocol for treating AUD comorbid with insomnia, and 2) using MED+CBT-I combination treatment to manage this subpopulation of AUD patients.

Being tested
Cognitive Behavioral Therapy for Insomnia, Sleep Hygiene Education
Keywords
Alcoholism, Sleep Initiation and Maintenance Disorders, Cognitive Behavioral Therapy
Medical subject headings
Alcoholism, Sleep Initiation and Maintenance Disorders

What participants receive

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

  • Cognitive Behavioral Therapy for InsomniaBehavioural

    Also called CBT-I

    CBT-I is conducted weekly for eight sessions during which the subjects meet individual with the study clinician for 45 minutes on the first session and for 30 minutes for sessions 2-8. Session 1 serves as an orientation and the onset of Sleep Restriction Therapy. Sessions 2 \& 3 deliver the three main components that include, Sleep Restriction Therapy, Stimulus control, and Sleep Hygiene. All the sessions excluding the last two sessions are dedicated to the titration of total sleep time and to ensure patient adherence. The fifth session is used to deliver a specific form of cognitive therapy. The final session is used to engage the patient in a relapse-prevention didactic (i.e., to review how insomnia becomes chronic and strategies that abort an extended episode of insomnia). The subject will return on week 9 to complete the post-intervention visit after 8 weeks of behavioral sleep treatment.

  • Sleep Hygiene EducationBehavioural

    Also called SHE

    This non-active control arm of behavioral sleep intervention consists of psychoeducation on sleep hygiene, sleep-related disturbances, and the effects of stress on sleep that will be delivered weekly for 8 weeks, for a time duration that is identical to the CBT-I sessions. The effect of stress on sleep is a commonly used control condition in insomnia clinical trials. SHE is preferred to a monitor-only condition as it will control for contact with the therapist and elapsed time during sessions. The subject will return on week 9 to complete the post-intervention visit after 8 weeks of behavioral sleep treatment.

Study groups in NCT04581603
Study groupRoleWhat they receive
MED + CBT-IActive comparatorThis arm will consist of patients treated with topiramate, naltrexone, or topiramate + naltrexone on a clinical basis for 6 weeks and then randomized to Cognitive Behavioral Therapy for Insomnia (CBT-I). They will be continued on MED for the next 8 weeks of CBT-I treatment.
Receives: Behavioral: Cognitive Behavioral Therapy for Insomnia
MED + SHEPlacebo comparatorThis arm will consist of patients treated with topiramate, naltrexone, or topiramate + naltrexone for 6 weeks on a clinical basis for 6 weeks and then randomized to Sleep Hygiene Education (SHE). They will be continued on MED for the next 8 weeks of SHE treatment.
Receives: Behavioral: Sleep Hygiene Education

What is being measured

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

  1. Change in Insomnia Severity Index - Total Score

    Insomnia Severity Index (ISI): This 7-item (0-4 Likert scales) measure yields a total score of 28. The norms for the scale are as follows: 0-7 represents no clinically significant insomnia; 8-14 represents sub threshold insomnia; 15-21 represents clinical insomnia (moderate severity); 21-28 represents clinical insomnia (severe). The scale provides a measure of severity of insomnia (overall), a measure of insomnia subtype, a measure of the diurnal effects of insomnia, and a measure of sleep "satisfaction". The ISI will be completed at baseline and for all the subsequent study-related visits.

    Measured: After eight weeks of behavioral sleep intervention

Secondary outcomes (3)
  1. Change in Percent Days Abstinent (PDA) on the Time Line Follow Back Measure

    Time Line Follow Back measure (TLFB): The TLFB provides assessment of drinking using a calendar format for the number of standard alcoholic beverages consumed per day. A standard drink, as defined by the National Institutes of Health, is 12 oz of regular beer, 5 oz of regular wine, or 1.5 oz of distilled spirits (e.g. whiskey). Numerous indices may be derived from the TLFB, such as the Percent Days Abstinent (PDA) proposed in this study. The PDA is derived as the percentage of days an individual reports being abstinent from alcohol within a given assessment time period.

    Measured: After eight weeks of behavioral sleep treatment

  2. Change in Percent Days Abstinent (PDA) on the Time Line Follow Back Measure

    Time Line Follow Back measure (TLFB): The TLFB provides assessment of drinking using a calendar format for the number of standard alcoholic beverages consumed per day. A standard drink, as defined by the National Institutes of Health, is 12 oz of regular beer, 5 oz of regular wine, or 1.5 oz of distilled spirits (e.g. whiskey). Numerous indices may be derived from the TLFB, such as the Percent Days Abstinent (PDA) proposed in this study. The PDA is derived as the percentage of days an individual reports being abstinent from alcohol within a given assessment time period.

    Measured: Eight weeks after end of behavioral sleep intervention (about 17 weeks since start of behavioral sleep treatment)

  3. Change in Insomnia Severity Index - Total Score

    Insomnia Severity Index (ISI): This 7-item (0-4 Likert scales) measure yields a total score of 28. The norms for the scale are as follows: 0-7 represents no clinically significant insomnia; 8-14 represents sub threshold insomnia; 15-21 represents clinical insomnia (moderate severity); 21-28 represents clinical insomnia (severe). The scale provides a measure of severity of insomnia (overall), a measure of insomnia subtype, a measure of the diurnal effects of insomnia, and a measure of sleep "satisfaction". The ISI will be completed at baseline and for all the subsequent study-related visits.

    Measured: Eight weeks after end of behavioral sleep intervention (about 17 weeks since start of behavioral sleep treatment)

Timeline

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

  1. First posted9 Oct 2020
  2. Study start15 Jun 2022
  3. Primary completion30 Jul 2024
  4. Study completion20 Jan 2025

Why it stopped: Difficulty recruiting patients

Resources

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 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Randomized, behavioral placebo-controlled trial.
Masking
Triple blind
Who is masked
Care provider, Investigator, Outcomes assessor
Enrolment
82 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04581603
Sponsor's protocol ID
NURA-001-19F
Other IDs
I01CX001957
Status last verified
Feb 2025
First submitted
2 Oct 2020
Last updated
28 Feb 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Cognitive Behavioral Therapy for Insomnia and Sleep Hygiene Education in people with Alcohol Use Disorder With Insomnia, run by VA Office of Research and Development at 2 sites 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 7 inclusion and 17 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 28 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

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

Are results available for this study?

The study was stopped early (reason given: Difficulty recruiting patients). Results are not available in the source record.

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?

Change in Insomnia Severity Index - Total Score (time frame: After eight weeks of behavioral sleep intervention). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
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 28 Feb 2025.

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