Suvorexant for PTSD-Related Sleep Disturbances

Recruiting at 3 trial locations

Overseen By Sabra S Inslicht, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: VA Office of Research and Development

Must be taking: SSRIs, SNRIs

Must not be taking: Benzodiazepines, Strong CYP3A inhibitors

Disqualifiers: Substance use disorder, Severe sleep apnea, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

144 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

Post-traumatic stress disorder (PTSD) is a common consequence of combat that can result in trauma-related hyperarousal and sleep disturbances. Poor sleep, one of the most common complaints in Veterans with PTSD, can be distressing, impair concentration and memory, and contribute to physical health conditions, such as metabolic syndrome, inflammation, and cardiovascular disease. The orexin neuropeptide system underlies both sleep and stress reactivity. Suvorexant, a drug that reduces orexin, improves sleep in civilians, but has not yet been tested in Veterans with PTSD. This study will test whether suvorexant can improve sleep disturbances and PTSD symptoms in Veterans. Suvorexant may benefit Veterans by improving sleep quickly while also reducing PTSD symptoms over the long term, and with fewer side effects that were common in previous medications used to treat these conditions. Improving Veterans' sleep and PTSD symptoms could lead to better emotional and physical well-being, quality of life, relationships, and functioning.

Will I have to stop taking my current medications?

You may need to stop taking certain medications like benzodiazepines, strong CYP3A inhibitors, or Digoxin, as they are not allowed during the trial. However, if you are on stable doses of certain antidepressants like SSRIs or SNRIs, you can continue taking them.

Is suvorexant safe for humans?

Suvorexant, approved for treating insomnia, is generally considered safe at doses of 5-20 mg, but it may cause next-morning sleepiness, muscle weakness, unusual dreams, sleepwalking, and other nighttime behaviors. It has been studied for up to 12 months in adults and elderly patients, with some concerns about its effects on driving and potential for misuse. ^{1 2 3 4 5}

How is the drug Suvorexant unique for treating PTSD-related sleep disturbances?

Suvorexant is unique because it is the first drug of its kind, a dual orexin receptor antagonist, which helps improve sleep by blocking wakefulness signals in the brain. Unlike other sleep medications, it can enhance REM sleep (a deep sleep stage) while reducing arousal, making it potentially beneficial for those with PTSD-related sleep issues. ^{1 2 4 5 6}

What data supports the effectiveness of the drug Suvorexant for PTSD-related sleep disturbances?

Suvorexant, a drug approved for treating insomnia, has been shown to improve sleep onset and maintenance, and enhance sleep quality. In studies, it has been found to increase deep sleep stages and reduce arousal, which may help with sleep disturbances in PTSD. ^{1 4 5 7 8}

Who Is on the Research Team?

Sabra S Inslicht, PhD

Principal Investigator

San Francisco VA Medical Center, San Francisco, CA

Are You a Good Fit for This Trial?

This trial is for US Veterans aged 18-75 with PTSD and sleep disturbances, not currently experiencing severe mental health crises or substance abuse. Participants must have stable medication use if applicable, no recent trauma exposure, and cannot be pregnant or planning pregnancy.

Inclusion Criteria

I am not pregnant, planning to become pregnant, or breastfeeding, and I will use birth control.

Criterion A event meets DSM-5 criteria

I am a veteran aged 18-75, can read English, and can consent to participate.

Exclusion Criteria

Previous adverse reaction to a hypnotic

DSM-5 alcohol, marijuana, and/or other drug use disorder in the last 3 months

Exposure to trauma in the last 3 months

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Titration

Participants undergo a 2-week titration period to adjust the dosage of suvorexant

2 weeks

Steady-dose Treatment

Participants receive a steady dose of suvorexant or placebo for the treatment of sleep disturbances and PTSD symptoms

10 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Suvorexant

Trial Overview The study tests Suvorexant's effectiveness in improving sleep and reducing PTSD symptoms compared to a placebo. It explores whether targeting the orexin system can provide relief with fewer side effects than previous treatments.

How Is the Trial Designed?

Group I: Suvorexant Experimental Treatment 1 Intervention

Suvorexant is a dual orexin receptor antagonist that is FDA approved to treat insomnia.

Group II: Identical Placebo Placebo Group 1 Intervention

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.

Suvorexant is already approved in United States, Japan for the following indications:

Approved in United States as Belsomra for:

• Insomnia characterized by difficulties with sleep onset and/or sleep maintenance

Approved in Japan as Belsomra for:

• Insomnia characterized by difficulties with sleep onset and/or sleep maintenance

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Published Research Related to This Trial

In a 6-week double-blind, placebo-controlled trial with 37 participants suffering from trauma-related insomnia, suvorexant treatment showed significant improvements in PTSD and insomnia symptoms, although the strong placebo response made it difficult to determine the medication's specific effects.

Suvorexant was well tolerated, with only one participant dropping out due to side effects, and it was associated with increased REM sleep duration, which correlated with a reduction in PTSD symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of suvorexant for trauma-related insomnia. Mellman, TA., Birku, K., Sandhu, I., et al.[2023]

This trial will assess the efficacy of suvorexant, an FDA-approved sleep aid, in reducing nighttime wakefulness and delirium in 120 older cardiac surgery patients in the ICU.

The study aims to determine if suvorexant can improve sleep quality and reduce the incidence of postoperative delirium, which is important for recovery in this vulnerable population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study protocol for a randomised controlled trial evaluating the effects of the orexin receptor antagonist suvorexant on sleep architecture and delirium in the intensive care unit. Azimaraghi, O., Hammer, M., Santer, P., et al.[2021]

Suvorexant, the first orexin receptor antagonist approved by the FDA for treating insomnia, has been shown to effectively induce and maintain sleep in adult and elderly patients over treatment periods of up to 12 months.

While the FDA approved doses of 5, 10, 15, and 20 mg due to concerns about safety and next-morning effects like somnolence and unusual behaviors, suvorexant represents a novel approach to insomnia treatment, potentially leading to new therapies targeting orexin receptors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Suvorexant for the treatment of insomnia. Jacobson, LH., Callander, GE., Hoyer, D.[2015]

In a randomized double-blind placebo-controlled trial involving adults with PTSD, the dual orexin receptor antagonist suvorexant improved sleep quality by increasing N3 sleep and enhancing between-session habituation to therapeutic exposure, suggesting potential benefits for PTSD treatment.

While suvorexant showed promise in enhancing the effects of therapeutic exposure, there was no significant difference in overall PTSD severity reduction compared to placebo, indicating that further research is needed to optimize treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blocking the orexin system following therapeutic exposure promoted between session habituation, but not PTSD symptom reduction. Kobayashi, I., Mellman, TA., Cannon, A., et al.[2023]

Suvorexant, an orexin receptor antagonist, was found to be generally safe and well tolerated over a 1-year treatment period for patients with primary insomnia, with a notable incidence of somnolence as a common side effect.

In the first month of treatment, suvorexant significantly improved subjective total sleep time by an average of 38.7 minutes and reduced time to sleep onset by 18.0 minutes compared to placebo, indicating its efficacy in enhancing sleep quality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of suvorexant during 1-year treatment of insomnia with subsequent abrupt treatment discontinuation: a phase 3 randomised, double-blind, placebo-controlled trial. Michelson, D., Snyder, E., Paradis, E., et al.[2022]

Suvorexant (Belsomra®) is a new sleep medication that works by blocking orexin neurons, leading to a rapid onset of sleep, and is effective at a prescribed dose of 10 mg before bedtime.

A highly sensitive urine assay was developed to accurately identify and quantify suvorexant, demonstrating excellent precision and stability, which is crucial for monitoring its use due to potential misuse and interactions with other sedatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of Suvorexant in Urine Using Liquid Chromatography-Quadrupole/Time-of-Flight Mass Spectrometry (LC-Q/TOF-MS). Sullinger, S., Bryand, K., Kerrigan, S.[2017]

Suvorexant is the first orexin receptor antagonist approved for treating insomnia, showing significant efficacy in reducing sleep latency and improving sleep maintenance in both non-elderly and elderly patients, based on two Phase 3 clinical trials with a total duration of 3 months.

The most common side effect was somnolence, with a number needed to harm (NNH) of 13 for higher doses, indicating that while suvorexant is effective, it does carry some risk of next-day sedation, leading to a recommended dose range of 10-20 mg.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Suvorexant for insomnia: a systematic review of the efficacy and safety profile for this newly approved hypnotic - what is the number needed to treat, number needed to harm and likelihood to be helped or harmed? Citrome, L.[2018]

Suvorexant is a first-in-class medication that works by blocking orexin receptors, which are involved in regulating wakefulness, thereby promoting sleep for individuals with insomnia.

Approved in the US in August 2014, suvorexant is effective for both sleep onset and sleep maintenance insomnia, and is in the process of being registered in other countries, indicating its potential global impact on treating sleep disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Suvorexant: first global approval. Yang, LP.[2021]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Evaluation of suvorexant for trauma-related insomnia. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Study protocol for a randomised controlled trial evaluating the effects of the orexin receptor antagonist suvorexant on sleep architecture and delirium in the intensive care unit. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Suvorexant for the treatment of insomnia. [2015]

4. England pubmed.ncbi.nlm.nih.gov

Blocking the orexin system following therapeutic exposure promoted between session habituation, but not PTSD symptom reduction. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of suvorexant during 1-year treatment of insomnia with subsequent abrupt treatment discontinuation: a phase 3 randomised, double-blind, placebo-controlled trial. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Identification of Suvorexant in Urine Using Liquid Chromatography-Quadrupole/Time-of-Flight Mass Spectrometry (LC-Q/TOF-MS). [2017]

7. India pubmed.ncbi.nlm.nih.gov

Suvorexant for insomnia: a systematic review of the efficacy and safety profile for this newly approved hypnotic - what is the number needed to treat, number needed to harm and likelihood to be helped or harmed? [2018]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Suvorexant: first global approval. [2021]