Suvorexant 3 - PE-PC
Suvorexant: Targeting Orexin to Augment Exposure Therapy in Veterans With PTSD and Insomnia
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.
調査の概要
状態
詳細な説明
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.
Relevance to Military Health: PTSD affects one in four treatment-seeking U.S. Veterans returning from Iraq and Afghanistan and one in 10 VA healthcare users. Sleep disturbance was the most frequently reported symptom in Veterans with PTSD, with the prevalence of insomnia or nonrestorative sleep estimated between 60%-90% and up to 97.4% of combat Veterans with TBI. However, effective and readily available treatments for co-occurring PTSD, insomnia, and TBI are not readily available or successful outside of PTSD specialty clinics, leading to unmet healthcare needs and/or treatment dropout/non-response. The ultimate goal of this work is to improve treatment availability and options for Veterans and military personnel affected by PTSD and TBI. Increased effectiveness of PTSD treatment in Veterans has the potential to: 1) optimize performance; 2) preserve health across the full deployment life cycle; and 3) improve long-term physical, social, and occupational functioning.
研究の種類
入学 (推定)
段階
- フェーズ 4
連絡先と場所
研究連絡先
- 名前:Sabra S Inslicht, PhD
- 電話番号:2-3341 415-221-4810
- メール:sabra.inslicht@va.gov
研究連絡先のバックアップ
- 名前:Bella S Benzaken, MA
- 電話番号:25116 415-221-4810
- メール:Bella.Benzaken@ncire.org
研究場所
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California
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San Francisco、California、アメリカ、94121-1545
- San Francisco VA Health Care System
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コンタクト:
- Sabra Inslicht, PhD
- 電話番号:3341 415-221-4810
- メール:Sabra.Inslicht@va.gov
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参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
研究計画
研究はどのように設計されていますか?
デザインの詳細
- 主な目的:処理
- 割り当て:ランダム化
- 介入モデル:並列代入
- マスキング:トリプル
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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アクティブコンパレータ:PE-PC + Suvorexant
PE-PC with suvorexant
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Suvorexant (10-20 mg) taken orally once nightly for 8 weeks, combined with weekly Prolonged Exposure for Primary Care (PE-PC) therapy sessions.
Suvorexant is an FDA-approved orexin receptor antagonist indicated for the treatment of insomnia.
Prolonged Exposure for Primary Care (PE-PC) is a briefer version of traditional Prolonged Exposure (PE) therapy, delivered in weekly sessions over 8 weeks.
PE-PC is designed to treat PTSD symptoms and related conditions such as insomnia and depression.
All study participants will receive PE-PC therapy regardless of their assigned intervention arm (suvorexant or placebo).
他の名前:
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プラセボコンパレーター:PE-PC + Placebo
PE-PC with placebo
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Prolonged Exposure for Primary Care (PE-PC) is a briefer version of traditional Prolonged Exposure (PE) therapy, delivered in weekly sessions over 8 weeks.
PE-PC is designed to treat PTSD symptoms and related conditions such as insomnia and depression.
All study participants will receive PE-PC therapy regardless of their assigned intervention arm (suvorexant or placebo).
他の名前:
A placebo pill taken orally once nightly for 8 weeks, combined with weekly Prolonged Exposure for Primary Care (PE-PC) therapy sessions.
The placebo is a look-alike substance that contains no active drug and is used as a comparator to evaluate the efficacy of suvorexant.
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この研究は何を測定していますか?
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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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
時間枠:Baseline (Week 0), Week 4 (Mid-Treatment), Week 8 (End of Treatment), and 6 months post-treatment; up to 32 weeks.
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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.
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Baseline (Week 0), Week 4 (Mid-Treatment), Week 8 (End of Treatment), and 6 months post-treatment; up to 32 weeks.
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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
時間枠: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.
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Baseline (Week 0), Week 4 (Mid-Treatment), Week 8 (End of Treatment), and 6 months post-treatment; up to 32 weeks
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Change from Baseline in Insomnia Severity as Assessed by the Insomnia Severity Index (ISI) at Week 4, Week 8, and 6 Months
時間枠:Baseline (Week 0), Week 4 (Mid-Treatment), Week 8 (End of Treatment), and 6 months post-treatment; up to 32 weeks
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The Insomnia Severity Index (ISI) is a 7-item self-report measure of insomnia severity.
Total scores range from 0 to 28, with higher scores indicating greater insomnia severity.
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Baseline (Week 0), Week 4 (Mid-Treatment), Week 8 (End of Treatment), and 6 months post-treatment; up to 32 weeks
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Change from Baseline in Objective Sleep Efficiency as Assessed by Wrist Actigraphy at Week 2, Week 4, Week 8, and 6 Months
時間枠:Baseline (Week 0), Week 4 (Mid-Treatment), Week 8 (End of Treatment), and 6 months post-treatment; up to 32 weeks
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Objective sleep efficiency will be assessed via wrist actigraphy worn continuously throughout the study.
Sleep efficiency is calculated as the percentage of time in bed spent asleep, ranging from 0% to 100%, with higher values indicating better sleep efficiency.
Sleep efficiency, sleep maintenance, total sleep time, and wake after sleep onset will be examined as secondary measures of sleep.
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Baseline (Week 0), Week 4 (Mid-Treatment), Week 8 (End of Treatment), and 6 months post-treatment; up to 32 weeks
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Change from Baseline in Subjective Sleep Efficiency as Assessed by Daily Sleep Diary at Week 2, Week 4, Week 8, and 6 Months
時間枠:Baseline (Week 0), Week 4 (Mid-Treatment), Week 8 (End of Treatment), and 6 months post-treatment; up to 32 weeks
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Subjective sleep efficiency will be assessed via daily self-reported sleep diary.
Sleep efficiency is calculated as the percentage of time in bed spent asleep, ranging from 0% to 100%, with higher values indicating better sleep efficiency.
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Baseline (Week 0), Week 4 (Mid-Treatment), Week 8 (End of Treatment), and 6 months post-treatment; up to 32 weeks
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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
時間枠:Baseline (Week 0), Week 4 (Mid-Treatment), Week 8 (End of Treatment), and 6 months post-treatment; up to 32 weeks
|
The B-IPF (Brief Inventory of Psychosocial Functioning) is a 7-item self-report measure assessing PTSD-related functional impairment in the past 30 days across seven functional domains, including romantic relationships, family relationships, work, friendships and socializing, parenting, education, and self-care.
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Baseline (Week 0), Week 4 (Mid-Treatment), Week 8 (End of Treatment), and 6 months post-treatment; up to 32 weeks
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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
時間枠: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 Quality of Life Assessment Brief Version (WHOQOL-BREF) is a 26-item instrument assessing quality of life across four domains: physical health, psychological health, social relationships, and environmental health.
Items are scored 1-5 and transformed to a standardized scale of 0-100, with higher scores indicating better quality of life.
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Baseline (Week 0), Week 4 (Mid-Treatment), Week 8 (End of Treatment), and 6 months post-treatment; up to 32 weeks
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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
時間枠:Baseline (Week 0), Week 4 (Mid-Treatment), Week 8 (End of Treatment), and 6 months post-treatment; up to 32 weeks
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The Engagement in Meaningful Activities Survey (EMAS) is a 12-item scale assessing meaningful activity participation.
Total scores range from 12 to 48, with higher scores indicating greater engagement in meaningful activities.
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Baseline (Week 0), Week 4 (Mid-Treatment), Week 8 (End of Treatment), and 6 months post-treatment; up to 32 weeks
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協力者と研究者
出版物と役立つリンク
一般刊行物
- Neylan TC, Marmar CR, Metzler TJ, Weiss DS, Zatzick DF, Delucchi KL, Wu RM, Schoenfeld FB. Sleep disturbances in the Vietnam generation: findings from a nationally representative sample of male Vietnam veterans. Am J Psychiatry. 1998 Jul;155(7):929-33. doi: 10.1176/ajp.155.7.929.
- Herring WJ, Connor KM, Ivgy-May N, Snyder E, Liu K, Snavely DB, Krystal AD, Walsh JK, Benca RM, Rosenberg R, Sangal RB, Budd K, Hutzelmann J, Leibensperger H, Froman S, Lines C, Roth T, Michelson D. Suvorexant in Patients With Insomnia: Results From Two 3-Month Randomized Controlled Clinical Trials. Biol Psychiatry. 2016 Jan 15;79(2):136-48. doi: 10.1016/j.biopsych.2014.10.003. Epub 2014 Oct 23.
- Kobayashi I, Mellman TA, Cannon A, Brown I, Boadi L, Howell MK, Lavela P, Sandhu I. Blocking the orexin system following therapeutic exposure promoted between session habituation, but not PTSD symptom reduction. J Psychiatr Res. 2022 Jan;145:222-229. doi: 10.1016/j.jpsychires.2021.12.027. Epub 2021 Dec 14.
- Rauch SAM, Kim HM, Acierno R, Ragin C, Wangelin B, Blitch K, Muzzy W, Hart S, Zivin K. Improving function through primary care treatment of posttraumatic stress disorder study outcomes: A randomized controlled trial of prolonged exposure for primary care in veterans. Fam Syst Health. 2023 Dec;41(4):502-513. doi: 10.1037/fsh0000823. Epub 2023 Aug 31.
- Gilbert KS, Kark SM, Gehrman P, Bogdanova Y. Sleep disturbances, TBI and PTSD: Implications for treatment and recovery. Clin Psychol Rev. 2015 Aug;40:195-212. doi: 10.1016/j.cpr.2015.05.008. Epub 2015 Jun 3.
- Wisco BE, Nomamiukor FO, Marx BP, Krystal JH, Southwick SM, Pietrzak RH. Posttraumatic Stress Disorder in US Military Veterans: Results From the 2019-2020 National Health and Resilience in Veterans Study. J Clin Psychiatry. 2022 Feb 22;83(2):20m14029. doi: 10.4088/JCP.20m14029.
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
キーワード
追加の関連 MeSH 用語
その他の研究ID番号
- 1874261
- HT94252510779 (その他の助成金/資金番号:DOD)
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD プランの説明
IPD 共有時間枠
IPD 共有アクセス基準
IPD 共有サポート情報タイプ
- STUDY_PROTOCOL
- SAP
- ICF
- ANALYTIC_CODE
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