Using suvorexant to improve sleep in veterans with PTSD

Suvorexant: A Dual Orexin Receptor Antagonist for Treating Sleep Disturbance inPosttraumatic Stress

This study is testing if the sleep medication suvorexant can help veterans with PTSD sleep better and feel less anxious.

Quick facts

• Phase: PHASE4
• Study type: Interventional
• Enrollment: 190 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: VA Office of Research and Development (fed)
• Drugs / interventions: imatinib
• Locations: 4 sites (Long Beach, California and 3 other locations)
• Trial ID: NCT03642028 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the efficacy and safety of suvorexant, a dual orexin receptor antagonist, in treating sleep disturbances and PTSD symptoms in veterans. The study employs a multi-site, randomized, double-blind, placebo-controlled design, with participants undergoing a 2-week dose titration followed by a 10-week steady-dose phase. The primary outcomes include changes in insomnia severity and PTSD symptoms, measured using validated scales. Additionally, the trial will explore the relationship between sleep improvement and PTSD symptom reduction, as well as the safety profile of suvorexant compared to placebo.

Who should consider this trial

Good fit: Ideal candidates are veterans aged 18 to 75 with a history of PTSD and insomnia lasting more than three months.

Not a fit: Patients who do not meet the PTSD criteria or have severe comorbid conditions may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve sleep quality and reduce PTSD symptoms in veterans, enhancing their overall well-being.

How similar studies have performed: Previous studies have shown that suvorexant is effective in improving sleep in civilian populations, but its efficacy in veterans with PTSD is being tested for the first time.

Eligibility criteria

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

Where this trial is running

Long Beach, California and 3 other locations

• VA Long Beach Healthcare System, Long Beach, CA — Long Beach, California, United States (RECRUITING)
• San Francisco VA Medical Center, San Francisco, CA — San Francisco, California, United States (RECRUITING)
• Salisbury W.G. (Bill) Hefner VA Medical Center, Salisbury, NC — Salisbury, North Carolina, United States (RECRUITING)
• Ralph H. Johnson VA Medical Center, Charleston, SC — Charleston, South Carolina, United States (RECRUITING)

Study contacts

• Principal investigator: Sabra S Inslicht, PhD — San Francisco VA Medical Center, San Francisco, CA
• Study coordinator: Sabra S Inslicht, PhD

Conditions: Sleep Initiation and Maintenance Disorders, Stress Disorders, Posttraumatic, Suvorexant, Veterans