Suvorexant for Treatment of AUD and PTSD

Официальное название

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)

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Suvorexant
  Suvorexant is described chemically as: \[(7R)-4-(5-chloro-2-benzoxazolyl) hexahydro-7-methyl-1H-1,4-diazepin-1-yl\]\[5-methyl-2-(2H-1,2,3-triazol2-yl)phenyl\]methanone. SUV's empirical formula is C23H23ClN6O2 and the molecular weight is 450.92. Each film coated tablet contains 10mg or 20mg of suvorexant.
• Другое Placebo
  Film coated tablet to match the active drug.

Первичные конечные точки

• Change in Insomnia Severity Index (ISI) score from baseline to Day 14. [Срок оценки: Baseline (Day 0) and Day 14]

Вторичные конечные точки (6)

• Change in cue-induced alcohol craving, as assessed by the Alcohol Urge Questionnaire (AUQ) during the alcohol condition, from baseline to day 14. [Срок оценки: Baseline (Day 0) and Day 14]
• Change in mean number of drinks per drinking day from baseline to Day 14. [Срок оценки: Baseline (Day 0) and Day 14]
• Percent total days abstinent during the 14-day quit attempt period. [Срок оценки: Baseline (Day 0) through Day 14]
• Change in the mean number of days abstinent during the medication period (day 0 through 14) compared to the 30-days prior (screening period). [Срок оценки: Screening (30-days prior to baseline) and Baseline through Day 14]
• 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. [Срок оценки: Baseline (Day 0) through Day 14]
• Change in PTSD score as measured by the PTSD Checklist for DSM-5 (PCL-5) from baseline to Day 14. [Срок оценки: Baseline (Day 0) through Day 14]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

США · 2 центра

• University of California - Los Angeles — Los Angeles
• The University of Texas Health Science Center - Houston — Houston

Публикации

• Ray LA, Nieto SJ, Miotto K, Mooney L, LeBeau R, Yoon JH, Schmitz JM, Acierno R, Bailey NW, Jenkins J, Vincent J, Nolen T, Hirsch S, Williams A, Lane SD. Suvorexant for alcohol use disorder and post-traumatic stress disorder: study protocol for a phase II randomized clinical trial. Trials. 2026 Feb 3;27(1):188. doi: 10.1186/s13063-026-09489-7. PMID 41630040

Идентификаторы

NCT: NCT06679062 · AS210006-A10

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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