CBT-I Augmentation of Medication for Drinking in AUD

NCT04581603 | Terminated Phase 4 DMC

• 2 other identifiers: NURA-001-19FI01CX001957
• Study Type: interventional
• Target: 82
• Locations: 1 country
• Sites: 2

Brief 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. 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.

Conditions

Alcohol Use Disorder With Insomnia

Keywords

Alcoholism; Sleep Initiation and Maintenance Disorders; Cognitive Behavioral Therapy

Outcome Measures

Primary Outcomes (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.

  After eight weeks of behavioral sleep intervention

Secondary Outcomes (3)

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

  After eight weeks of behavioral sleep treatment

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

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

• Change in Insomnia Severity Index - Total Score

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

Study Arms (2)

MED + CBT-I

ACTIVE COMPARATOR

This 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.

Behavioral: Cognitive Behavioral Therapy for Insomnia

MED + SHE

PLACEBO COMPARATOR

This 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.

Behavioral: Sleep Hygiene Education

Interventions

Cognitive Behavioral Therapy for Insomnia BEHAVIORAL

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.

Also known as: CBT-I

MED + CBT-I

Sleep Hygiene Education BEHAVIORAL

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.

Also known as: SHE

MED + SHE

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• VA Office of Research and Development: lead
• Coatesville Veterans Affairs Medical Center: collaborator

Study Sites (2)

Coatesville VA Medical Center, Coatesville, PA

Coatesville, Pennsylvania, 19320, United States

Location

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

Philadelphia, Pennsylvania, 19104-4551, United States

Location

MeSH Terms

Conditions

Alcoholism; Sleep Initiation and Maintenance Disorders

Interventions

Cognitive Behavioral Therapy

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities

Study Officials

• Subhajit Chakravorty, MD

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: single-blind.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: Randomized, behavioral placebo-controlled trial.

Study Record Dates

• First Submitted: October 2, 2020
• First Posted: October 9, 2020
• Study Start: June 15, 2022
• Primary Completion: July 30, 2024
• Study Completion: January 20, 2025
• Last Updated: February 28, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)