Clinical trial NCT06679062: Suvorexant for Treatment of AUD and PTSD
Official title: A Double-masked, Randomized, Phase II Study to Compare the Effectiveness of 20mg Oral Suvorexant (SUV) Versus Placebo (1:1) in Participants With Co-occurring Alcohol Use Disorder (AUD) and Posttraumatic Stress Disorder (PTSD)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Alcohol Use Disorder (AUD)
Post Traumatic Stress Disorder (PTSD)
Insomnia
Lead sponsor: Pharmacotherapies for Alcohol and Substance Use Disorders Alliance
Sponsor class: OTHER
Collaborators: name: University of California, Los Angeles
name: The University of Texas Health Science Center, Houston
First posted: 2024-11-07
Enrollment: 76
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Each participant will be given a placebo run-in (Day -7 to Day -1). On baseline (Day 0), the participant will be randomized to receive SUV or placebo (1:1 ratio) and administered 10mg SUV or placebo for an additional 7 days (Day 0 to Day 6). On Day 7, the participant previously randomized to SUV will be given 20 mg SUV, and participant previously randomized to placebo will continue with placebo.
Primary purpose: TREATMENT

Brief summary: This study is to determine if suvorexant (SUV) will reduce insomnia in 76 men and women veteran and non-veterans between the ages 21-65 with posttraumatic stress disorder (PTSD) symptoms and alcohol use disorder (AUD). All participants will have a 7-day placebo run-in period, followed by a random assignment to receive placebo or suvorexant for an additonal 14 days. Post-randomization, participants will attempt to stop drinking for two weeks and will complete daily virtual diaries and study outcome assessments via in-person clinic visits on days 7 and 14.

Detailed description: This is a randomized, double-masked, placebo-controlled study to evaluate preliminary efficacy and safety of suvorexant (SUV) (20mg) for sleep disturbance in alcohol use disorder (AUD) and co-occurring posttraumatic stress disorder (PTSD) symptoms in approximately 76 randomized men and women veteran and non-veterans between the ages 21-65. Participants will be recruited from the University of Texas Health Science Center at Houston (UTHealth) Trauma and Recovery Center (TRC) and the University of California - Los Angeles (UCLA) (in collaboration with West Los Angeles VA Medical Center). Following a 7-day placebo run-in, participants will be randomly assigned to receive SUV (10mg (Days 0-6) and 20mg (Days 7-13)) or matched placebo. Randomization will be stratified on sex and level of sleep disturbance (Insomnia Severity Index (ISI) score). Post-randomization, all participants will complete an alcohol cue-reactivity paradigm prior to the initial dose of study medication. The alcohol cue-reactivity paradigm is an established laboratory assessment of craving during which participants are exposed to real alcohol and water cues in a bar laboratory setting. Participants will then take their first dose of medication. Participants will begin the real-world quit attempt, during which they will attempt to stop drinking for two weeks. Participants will complete daily virtual diaries and visits to assess sleep, past-day drinking, and alcohol craving. Participants will return to one of the clinical sites on study Day 14 to complete an alcohol cue-reactivity session to assess post-medication craving. PTSD symptoms will be assessed via Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (CAPS-5) and Post-traumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (PCL-5) at baseline, at Day 7 and at Day 14 of treatment with SUV or matched placebo.

Eligibility criteria: Inclusion Criteria:

* Age between 21 and 65.
* Meet current (i.e., past 12-month at Day -7/-6) DSM-5 diagnostic criteria for moderate or severe AUD as determined by the MINI.
* Currently experiencing PTSD symptoms at screening (Day -7/-6) as indicated by PCL-5 cut-score \> 30.
* Intrinsic motivation to reduce or quit drinking (defined as self-reported intention at screening to reduce or quit drinking within the next 6 months) and to receive PTSD treatment.
* Must have an ISI score equal to or \> 7 (subthreshold insomnia). ISI score below 7 at screening will not be included or proceed beyond the screening day.
* Agree to abstain from all other sleep medications (starting at Day -7).
* Have a place to live in the 2 weeks prior to randomization (Day 0) and not be at risk that s/he will lose his/her housing in the next month.

Exclusion Criteria:

* A current (past 12-month at Day -7/-6) DSM-5 diagnosis via the MINI of substance use disorder for any substances other than alcohol, nicotine, or marijuana (\< moderate level on DSM 5).
* A lifetime DSM-5 diagnosis via the MINI of schizophrenia, bipolar disorder, or psychotic disorder.
* Positive urine test for any recreational drugs other than marijuana at screening (Day -7/-6).
* Current clinically significant alcohol withdrawal (i.e., score ≥ 10 on the CIWA-Ar).
* Currently pregnant, nursing, or no reliable method of birth control (females only).
* Any clinically significant medical condition that would preclude safe participation in the study (e.g. narcolepsy, seizure disorder, or other clinically significant cardiovascular, hematologic, hepatic, renal, neurological, or endocrine disorders).
* Use of suvorexant (within 30 days of Day -7).
* Currently on prescription medication that contraindicates use of suvorexant (including moderate or strong Cytochrome P450 3A modulators (CYP3A inhibitors and inducers))
* Hepatic insufficiency (AST/ALT \> 5x upper limit of normal (ULN)).
* Suicidal Ideation determined by greater than moderate Columbia Suicide Severity Rating Scale.
* Inability to provide evidence of 48-hour alcohol abstinence (self-report, BrAC, EtG) at Day 0 AND failure after second attempt at 48-hour abstinence.

Primary outcomes:
measure: Change in Insomnia Severity Index (ISI) score from baseline to Day 14.
timeFrame: Baseline (Day 0) and Day 14
Secondary outcomes:
measure: Change in cue-induced alcohol craving, as assessed by the Alcohol Urge Questionnaire (AUQ) during the alcohol condition, from baseline to day 14.
timeFrame: Baseline (Day 0) and Day 14
measure: Change in mean number of drinks per drinking day from baseline to Day 14.
timeFrame: Baseline (Day 0) and Day 14
measure: Percent total days abstinent during the 14-day quit attempt period.
timeFrame: Baseline (Day 0) through Day 14
measure: Change in the mean number of days abstinent during the medication period (day 0 through 14) compared to the 30-days prior (screening period).
timeFrame: Screening (30-days prior to baseline) and Baseline through Day 14
measure: Change in PTSD total symptom severity score as measured by the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) from baseline to Day 14.
timeFrame: Baseline (Day 0) through Day 14
measure: Change in PTSD score as measured by the PTSD Checklist for DSM-5 (PCL-5) from baseline to Day 14.
timeFrame: Baseline (Day 0) through Day 14
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California - Los Angeles
state: California
city: Houston
country: United States
facility: The University of Texas Health Science Center - Houston
state: Texas
Study officials:
affiliation: The University of Texas Health Science Center, Houston
name: Scott Lane, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, Los Angeles
name: Lara Ray, PhD
role: PRINCIPAL_INVESTIGATOR
References: