Suvorexant: Targeting Orexin to Augment Exposure Therapy in Veterans With PTSD and Insomnia
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 142
- 试验地点
- 1
- 主要终点
- Change from Baseline in PTSD Symptom Severity as Assessed by the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) at Week 4, Week 8, and 6 Months
研究概览
简要总结
The goal of this clinical trial is to learn if combining suvorexant (a sleep medication) with a shorter form of prolonged exposure therapy called PE-PC works to treat PTSD symptoms and improve sleep in Veterans and military personnel with PTSD and insomnia, with and without mild-to-moderate traumatic brain injury (TBI). The main questions it aims to answer are:
Does suvorexant, when combined with PE-PC therapy, reduce PTSD symptoms more than PE-PC with a placebo (a look-alike substance that contains no drug)? Does suvorexant, when combined with PE-PC therapy, improve psychosocial and physical functioning more than PE-PC with a placebo?
Researchers will compare PE-PC combined with suvorexant to PE-PC combined with a placebo to see if adding suvorexant improves PTSD symptoms, sleep, and overall functioning in Veterans.
Participants will:
Receive weekly PE-PC therapy sessions for 8 weeks Take suvorexant (10-20 mg) or a placebo each night during the 8-week treatment period.
Complete repeated assessments of PTSD symptoms, sleep, and psychosocial and physical functioning throughout the study.
详细描述
Insomnia is the most prevalent symptom endorsed by PTSD patients and is highly prevalent in TBI, resulting in impairments in many domains of overall health and functioning. Prolonged exposure for primary care (PE-PC) is a shorter version of traditional PE that has demonstrated efficacy in the treatment of PTSD, related conditions (e.g., insomnia, depression), and improving functioning when compared to treatment as usual (e.g., PE, cognitive behavioral therapy for insomnia) in Veterans. However, challenges for PTSD interventions remain as some symptoms, particularly arousal and sleep-related difficulties, often fail to remit, with only 40-60% of Veterans showing clinically significant improvements following treatment, in addition to high attrition rates from these interventions. An integrated treatment that incorporates a pharmacological intervention that improves sleep during PE-PC may provide the greatest opportunity to facilitate recovery, by both increasing Veterans' engagement in treatment and supporting the extinction learning and consolidation mechanisms that promote recovery.
Hypothesis/Objective(s): The investigators aim to test whether integrating PE-PC with suvorexant, FDA-approved for the treatment of insomnia, will 1) promote the efficacy of PE-PC in improving sleep and PTSD symptoms in Veterans and military personnel with insomnia and posttraumatic stress disorder (PTSD) with and without mild-to-moderate traumatic brain injury (TBI); and 2) improve psychosocial and physical functioning.
Specific Aims: 1) To examine whether suvorexant facilitates PE-PC, seen as a greater reduction of PTSD symptoms over the course of treatment. 2) To examine whether suvorexant facilitates greater improvement in psychosocial and physical functioning compared to placebo over the course of treatment.
Study Design: The investigators propose an 8-week randomized, double-blind, placebo-controlled Phase IV clinical trial to examine the efficacy of augmenting PE-PC with suvorexant (10-20 mg) for the treatment of PTSD symptoms and improvement of functioning in Veterans with PTSD, insomnia, with and without TBI. The study design (N = 142) will involve repeated measures with two intervention arms, both of which include a standard course of weekly PE-PC therapy: 1) PE-PC+suvorexant (n = 71) compared to 2) PE-PC+placebo (n = 71).
Clinical Impact: This work aligns with the FY24 TBIPHRP CTA Research Level 2, Focus Area to Treat by examining repurposed interventions to improve outcomes of psychological health conditions and/or TBI through treatment and rehabilitation. The proposed intervention could promote sustained functional recovery following insomnia, PTSD, and TBI, as well as increased treatment engagement, retention, and success in those Veterans who would have otherwise not responded to treatment.
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, Investigator, Outcomes Assessor)
盲法说明
Study Coordinators
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults 18-75 years who are U.S. military Veterans; able to read/understand English and provide written informed consent;
- •Exposure to a DSM-5 Criterion A traumatic event;
- •Current PTSD, duration > 3 months, CAPS-5 total score ≥ 12
- •Insomnia diagnosis indicated by ISI score >14
- •If taking non-exclusionary psychotropics (e.g., SSRI/SNRI, tetracyclic antidepressants, tricyclics, antipsychotics, and mood stabilizers, insomnia medication, neuroleptics, anti-psychotics) must be on a dose stable ≥ 4 weeks before randomization.
- •If in supportive psychotherapy, stable ≥ 6 weeks before randomization (no concurrent exposure-based PTSD or CBT-I).
- •Women of childbearing potential: negative urine pregnancy test at screening; agree to use a medically acceptable contraception method during treatment.
排除标准
- •DSM-5 alcohol, marijuana, and/or other substance use disorder in the last 3 months. Mild alcohol and marijuana use not meeting criteria for disorder permissible;
- •Lifetime bipolar disorder I or II, schizophrenia, schizoaffective disorder, obsessive-compulsive disorder, or major depressive disorder with psychotic features;
- •Exposure to trauma in the last 3 months;
- •Prominent suicidal or homicidal ideation, any suicidal behavior in the past 3 months on the Columbia Suicide Severity Rating Scale (C-SSRS)83, or increased risk of suicide that necessitates additional therapy or inpatient treatment;
- •Pre-existing sleep apnea by type III device with AHI >15 in the absence of adherence to effective treatment (such as CPAP or oral device);
- •Night shift work or extreme morning or evening tendencies;
- •Neurologic disorder or systemic illness affecting CNS function;
- •Chronic or unstable medical illness (i.e., angina, myocardial infarction within the past 6 months, congestive heart failure, preexisting hypotension or orthostatic hypotension, heart block or arrhythmia, chronic renal or hepatic failure, pancreatitis, and severe chronic obstructive pulmonary disease);
- •Severe cognitive impairment as assessed by the MoCA (or alternative validated threshold per site SOP)
- •Pregnancy or breastfeeding, or unwillingness to use effective contraception (women of childbearing potential).
- •Previous adverse reaction to a hypnotic;
- •Current use of sedative-hypnotics, benzodiazepines, moderate or strong CYP3A inhibitors, or strong CYP3A inducers or Digoxin;
- •Current participation in exposure-based PTSD or behavioral insomnia treatments.
结局指标
主要结局
Change from Baseline in PTSD Symptom Severity as Assessed by the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) at Week 4, Week 8, and 6 Months
时间窗: Baseline (Week 0), Week 4 (Mid-Treatment), Week 8 (End of Treatment), and 6 months post-treatment; up to 32 weeks.
The Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) is a 30-item clinician-administered interview measuring the frequency and intensity of PTSD symptoms. Total scores range from 0 to 80, with higher scores indicating greater PTSD symptom severity.
Change from Baseline in Overall Functioning as Assessed by the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) at Week 4, Week 8, and 6 Months
时间窗: Baseline (Week 0), Week 4 (Mid-Treatment), Week 8 (End of Treatment), and 6 months post-treatment; up to 32 weeks
The World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) is a 36-item self-administered measure assessing functional ability across six domains. Summary scores range from 0 to 100, with higher scores indicating greater disability.
次要结局
- Change from Baseline in Insomnia Severity as Assessed by the Insomnia Severity Index (ISI) at Week 4, Week 8, and 6 Months(Baseline (Week 0), Week 4 (Mid-Treatment), Week 8 (End of Treatment), and 6 months post-treatment; up to 32 weeks)
- Change from Baseline in Objective Sleep Efficiency as Assessed by Wrist Actigraphy at Week 2, Week 4, Week 8, and 6 Months(Baseline (Week 0), Week 4 (Mid-Treatment), Week 8 (End of Treatment), and 6 months post-treatment; up to 32 weeks)
- Change from Baseline in Subjective Sleep Efficiency as Assessed by Daily Sleep Diary at Week 2, Week 4, Week 8, and 6 Months(Baseline (Week 0), Week 4 (Mid-Treatment), Week 8 (End of Treatment), and 6 months post-treatment; up to 32 weeks)
- Change from Baseline in Psychosocial Functioning as Assessed by the Brief Inventory of Psychosocial Functioning (B-IPF) at Week 4, Week 8, and 6 Months(Baseline (Week 0), Week 4 (Mid-Treatment), Week 8 (End of Treatment), and 6 months post-treatment; up to 32 weeks)
- Change from Baseline in Quality of Life as Assessed by the World Health Organization Quality of Life Assessment Brief Version (WHOQOL-BREF) at Week 4, Week 8, and 6 Months(Baseline (Week 0), Week 4 (Mid-Treatment), Week 8 (End of Treatment), and 6 months post-treatment; up to 32 weeks)
- Change from Baseline in Engagement in Meaningful Activities as Assessed by the Engagement in Meaningful Activities Survey (EMAS) at Week 4, Week 8, and 6 Months(Baseline (Week 0), Week 4 (Mid-Treatment), Week 8 (End of Treatment), and 6 months post-treatment; up to 32 weeks)