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)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 76
- 试验地点
- 4
- 主要终点
- Change in Insomnia Severity Index (ISI) score from baseline to Day 14.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
To minimize bias, all participants will be screened for assurance that they meet study eligibility criteria. A placebo drug will be employed as the comparison group to active study drug and the study will be conducted in a double-blinded fashion in that both the participants and the site investigators and staff interacting with participants and assessing study outcomes will be blinded to treatment assignment. The only individuals at the site with access to treatment assignment information will be the research pharmacists.
入排标准
- 年龄范围
- 21 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age between 21 and
- •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 >
- •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.
排除标准
- •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.
研究组 & 干预措施
Placebo
Participants will be randomly assigned to receive matched placebo (Days 0-13).
干预措施: Placebo (Other)
10mg and 20mg Suvorexant (SUV)
Participants will be randomly assigned to receive SUV (10mg (Days 0-6) and 20mg (Days 7-13)).
干预措施: Suvorexant (Drug)
结局指标
主要结局
Change in Insomnia Severity Index (ISI) score from baseline to Day 14.
时间窗: Baseline (Day 0) and Day 14
The Insomnia Severity Index (ISI) is a brief questionnaire to screen for insomnia in participants. A scoring system is used to identify what degree insomnia (if any detected) is affecting daily life and sleep patterns. A total score is derived by summing all seven items with a total score ranging from 0 to 28 (with higher scores indicative of worse insomnia symptoms).
次要结局
- Change in cue-induced alcohol craving, as assessed by the Alcohol Urge Questionnaire (AUQ) during the alcohol condition, from baseline to day 14.(Baseline (Day 0) and Day 14)
- Change in mean number of drinks per drinking day from baseline to Day 14.(Baseline (Day 0) and Day 14)
- Percent total days abstinent during the 14-day quit attempt period.(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).(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.(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.(Baseline (Day 0) through Day 14)