- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03642028
Suvorexant: A Dual Orexin Receptor Antagonist for Treating Sleep Disturbance in Posttraumatic Stress
Suvorexant: A Dual Orexin Receptor Antagonist for Treating Sleep Disturbance inPosttraumatic Stress
Study Overview
Status
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Estimated)
Phase
- Phase 4
Contacts and Locations
Study Contact
- Name: Sabra S Inslicht, PhD
- Phone Number: 3341 (415) 221-4810
- Email: sabra.inslicht@va.gov
Study Locations
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California
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Long Beach, California, United States, 90822
- Not yet recruiting
- VA Long Beach Healthcare System, Long Beach, CA
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Contact:
- PhD
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Contact:
- Michael Hollifield, MD
- Phone Number: 562-967-0115
- Email: Michael.Hollifield@va.gov
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San Francisco, California, United States, 94121-1563
- Recruiting
- San Francisco VA Medical Center, San Francisco, CA
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Contact:
- Sabra S Inslicht, PhD
- Phone Number: 3341 415-221-4810
- Email: sabra.inslicht@va.gov
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Principal Investigator:
- Sabra S Inslicht, PhD
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North Carolina
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Salisbury, North Carolina, United States, 28144
- Recruiting
- Salisbury W.G. (Bill) Hefner VA Medical Center, Salisbury, NC
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Contact:
- Robin Hurley, MD
- Phone Number: 14455 704-638-9000
- Email: robin.hurley@va.gov
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Contact:
- Amy Morris
- Phone Number: 14392 7046389000
- Email: amy.morris3@va.gov
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South Carolina
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Charleston, South Carolina, United States, 29401-5703
- Recruiting
- Ralph H. Johnson VA Medical Center, Charleston, SC
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Contact:
- Zhewu Wang, MD
- Phone Number: 843-252-3586
- Email: zhewu.wang@va.gov
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Contact:
- Lisa McTeague, PhD
- Phone Number: 8435775011
- Email: lisa.mcteague@va.gov
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Men and Women, age range of 18 to 75, with a history of US military service, capable of reading and understanding English, and able to provide written informed consent
- Criterion A event meets DSM-5 criteria
- PTSD symptoms >3 months duration as indexed by a CAPS-5 12 and a partial PTSD diagnosis at screening
- Insomnia indicated by an ISI score > 14
Subjects on non-exclusionary medications must be on a stable dose for at least 4 weeks prior to randomization, which includes the Selective Serotonin Reuptake Inhibitors (SSRIs) e.g.:
- Sertraline
- Paroxetine
- Fluoxetine
- Fluvoxamine
- Citalopram
- Escitalopram
Serotonin-norepinephrine reuptake inhibitors (SNRIs), e.g.:
- Desvenlafaxine
- Duloxetine
- Levomilnacipran
- Venlafaxine
- For subjects who are in psychotherapy, treatment must be stable for 6 weeks
Women of child-bearing potential must not be pregnant or have plans for pregnancy or breastfeeding during the study and must use a medically acceptable method of birth control, e.g.:
- oral
- implantable
- injectable
- transdermal contraceptive
- intrauterine device
- double-barrier method
- Sleep apnea score <30; if screening indicates mild or moderate sleep apnea (score between 5 and 30), referral will be provided
Exclusion Criteria:
DSM-5 alcohol, marijuana, and/or other drug use disorder in the last 3 months
- Mild alcohol use not meeting criteria for moderate or severe use disorder may be allowed on a case-by-case basis
- Mild or moderate marijuana use disorder may be allowed on a on a case-by-case basis
- Manic or psychotic episode in the last 5 years
- Exposure to trauma in the last 3 months
- Prominent suicidal or homicidal ideation or any suicidal behavior in the past 3 months on the Columbia Suicide Severity Rating Scale (C-SSRS) or increased risk of suicide that necessitates additional therapy or inpatient treatment
- Pre-existing severe sleep apnea (score >30) in the absence of adherence to effective treatment (such as CPAP or oral device) or positive screen for severe sleep apnea by type III device (score > 30)
- Neurologic disorder or systemic illness affecting CNS function
Chronic or unstable medical illness including:
- unstable 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
- severe chronic obstructive pulmonary disease
- History of severe traumatic brain injury
- Mild cognitive impairment assessed by the Montreal Cognitive Assessment
- Pregnancy, breastfeeding and/or refusal to use effective birth control (for women)
- Narcolepsy
- Previous adverse reaction to a hypnotic
- Current use of benzodiazepines, strong CYP3A inhibitors, or Digoxin
Prohibited:
- benzodiazepines
- strong CYP3A inhibitors
- Digoxin
- Furthermore, CNS depressants (e.g., benzodiazepines, opioids, alcohol) increase the risk of CNS depression when co-administered with suvorexant and will not be allowed for safety reasons.
- Since metabolism by CYP3A is the major elimination pathway for suvorexant, concomitant use of suvorexant with strong inhibitors of CYP3A (e.g., ketoconazole, itraconazole, posaconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, boceprevir, telaprevir, telithromycin and conivaptan), moderate CYP3A inhibitors (e.g., amprenavir, aprepitant, atazanavir, ciprofloxacin, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice, imatinib, verapamil), or strong CYP3A inducers (e.g., rifampin, carbamazepine and phenytoin) will not be allowed.
- All concomitant medication use will be monitored and documented
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Suvorexant
Suvorexant is a dual orexin receptor antagonist that is FDA approved to treat insomnia.
|
Suvorexant, a dual orexin receptor antagonist, is the first in a new class of drugs with great promise of addressing insomnia in Veterans with PTSD.
Suvorexant targets the orexin neuropeptide system and has been shown to be highly successful in treating insomnia.
Other Names:
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Placebo Comparator: Identical Placebo
Visibly matched, equally weighted placebo tablets.
In addition to matching in appearance and weight, they will have identical packaging and labeling as randomized, blinded study medication.
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Visibly matched, equally weighted placebo tablets.
In addition to matching in appearance and weight, they will have identical packaging and labeling as randomized, blinded study medication.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Insomnia Severity Index (ISI)
Time Frame: Change from baseline to week 12
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The ISI is a specific index of perceived insomnia severity.
Areas assessed include problems with sleep onset, sleep maintenance, and early morning awakening; dissatisfaction with sleep; interference with daily functioning; impact on quality of life; and worry about sleep problems.
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Change from baseline to week 12
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Clinician Administered PTSD Scale for DSM-5 (CAPS-5)
Time Frame: Change from baseline to week 12
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The CAPS-5 is a 30-item interview that is the gold standard assessment for PTSD.
The CAPS-5 provides a dimensional and categorical measure of PTSD, and incorporates frequency and intensity of symptoms into a single severity score.
The CAPS-5 will determine a threshold for PTSD severity (past week) at baseline (excluding change in item #20 falling and staying asleep).
Possible scores range from 0 to 80.
All trained and certified CAPS-raters will function independently and will not be involved in recruitment, study coordination, or evaluation of side effects.
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Change from baseline to week 12
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Wrist Actigraphy
Time Frame: Change from 1 week at baseline, and weeks 4, 8, and 12
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Sleep wake schedule will be monitored with wrist actigraphy (Micro Motionlogger, Ambulatory Monitoring, Inc.).
The actigraph provides continuous activity data using a battery-operated wristwatch-size microprocessor that senses motion with a three axis accelerometer.
High-resolution data will be down-sampled to one-minute sample intervals for conventional actigraphic sleep-wake estimation and analyzed using ActionW-2 (Ambulatory Monitoring, Inc.) software.
Sleep efficiency, sleep maintenance, total sleep time and wake after sleep onset will be used as secondary measures of sleep.
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Change from 1 week at baseline, and weeks 4, 8, and 12
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Pittsburgh Sleep Quality Index-PTSD Addendum (PSQI-A)
Time Frame: Change in PTSD-related nightmares across the 12 week trial
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PSQI-A will be used to assess disruptive nocturnal behaviors related to PTSD, including nightmares, hot flashes and episodes of terror during sleep.
Scores ranges from 0 (normal) to 21 (severe).
The investigators plan to evaluate nightmares as a secondary outcome.
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Change in PTSD-related nightmares across the 12 week trial
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Clinical Global Impression (CGI)
Time Frame: Change across the 12 week trial
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The Clinician and patient reports of improvement on the CGI (depression, mood, vigor, suicidality, daytime somnolence, and functional disability rating scales.)
The CGI measures psychiatric treatment response by evaluating global severity of illness and change in the clinical condition over time.
It consists of 3 global subscales: Severity of Illness, Global Improvement, and Efficacy Index.
Item 1 is rated on a seven-point scale (1=normal to 7=extremely ill); item 2 on a seven-point scale (1=very much improved to 7=very much worse); and item 3 on a four-point scale (from 'none' to 'outweighs therapeutic effect').
The CGI will be used as a secondary measure of remission (i.e., CGI-I of 1 "very much improved" or 2 "much improved").
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Change across the 12 week trial
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Collaborators and Investigators
Investigators
- Principal Investigator: Sabra S Inslicht, PhD, San Francisco VA Medical Center, San Francisco, CA
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Mental Disorders
- Nervous System Diseases
- Sleep Disorders, Intrinsic
- Sleep Wake Disorders
- Trauma and Stressor Related Disorders
- Sleep Initiation and Maintenance Disorders
- Stress Disorders, Traumatic
- Stress Disorders, Post-Traumatic
- Dyssomnias
- Parasomnias
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Hypnotics and Sedatives
- Sleep Aids, Pharmaceutical
- Orexin Receptor Antagonists
- Suvorexant
Other Study ID Numbers
- MHBB-009-17F
- 1I01CX001814-01 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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