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

190 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether suvorexant, a medication already used to aid sleep, can also improve sleep and PTSD symptoms in Veterans. The focus is on Veterans who have experienced PTSD symptoms for more than three months and struggle with insomnia. Participants will receive either suvorexant or a placebo (a pill with no active medicine) to evaluate the drug's effectiveness. Veterans with PTSD-related sleep problems who are not currently using certain medications may be suitable for this trial. As a Phase 4 trial, this research aims to understand how the already FDA-approved treatment benefits more patients.

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.

What is the safety track record for Suvorexant?

Research has shown that suvorexant, a drug approved by the FDA for treating insomnia, is generally well-tolerated. Studies have found it to be safe and effective for improving sleep in individuals with sleep problems related to trauma and conditions like Alzheimer's disease.

Suvorexant works by blocking orexin, a brain chemical that influences sleep and wakefulness, helping people fall asleep and stay asleep longer. Safety reports indicate that suvorexant is used without major side effects, making it a promising option for those with sleep issues, even in cases of PTSD. While some individuals might experience mild side effects like drowsiness, the overall safety profile remains positive. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard treatments for PTSD-related sleep disturbances, which often involve antidepressants or benzodiazepines, Suvorexant acts as a dual orexin receptor antagonist. This means it targets the brain's orexin system, which is responsible for wakefulness, helping to promote sleep without the same risk of dependency or side effects associated with other medications. Researchers are excited about Suvorexant because it offers a novel approach by directly addressing sleep issues, potentially leading to a better quality of rest for those with PTSD.

What evidence suggests that suvorexant might be an effective treatment for PTSD-related sleep disturbances?

Research has shown that suvorexant, a medication that blocks certain brain signals, can improve sleep in people with insomnia. One study demonstrated significant improvements in both PTSD and insomnia symptoms among participants. Suvorexant blocks the orexin system, which controls sleep and stress. It increases deep sleep and reduces the time to enter REM (rapid eye movement) sleep, benefiting those with PTSD. The drug is already approved for treating insomnia, proving its effectiveness in improving sleep quality. In this trial, some participants will receive suvorexant to evaluate its potential to help Veterans with PTSD manage sleep problems. ^{1 3 4 6 7}

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

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]

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 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]

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]

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]

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 (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, 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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35554590/

Evaluation of suvorexant for trauma-related insomnia Results: The thirty-seven evaluable participants had significant improvement of PTSD and insomnia symptoms, however, there were no significant ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02704754

NCT02704754 | Suvorexant and Trauma Related Insomnia The investigators hypothesize that suvorexant will improve subjective and objective indices of sleep disturbance; specifically, our primary outcome the ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0022395621007299

Blocking the orexin system following therapeutic exposure ... We found that suvorexant increased N3 sleep and decreased N2 sleep and rapid-eye-movement latency measured by polysomnography.

4. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT06788522

The Effects of Orexin Antagonism on Fear Extinction in PTSD This study will examine whether suvorexant, a selective orexin-receptor antagonist, will enhance fear extinction in Veterans with PTSD and insomnia.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03642028

Study Details | NCT03642028 | Suvorexant: A Dual Orexin ... It has outstanding promise for treating common and distressing symptoms in Veterans as well as civilians with trauma-related sleep disturbance and PTSD.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02750306

NCT02750306 | Safety and Efficacy of Suvorexant (MK- ... This study aims to examine the safety and efficacy of suvorexant (MK-4305) to improve sleep in individuals with Alzheimer's disease (AD).

7. tga.gov.au tga.gov.au/sites/default/files/auspar-suvorexant-150411.pdf

Australian Public Assessment Report for Suvorexant The pharmacological studies demonstrated receptor selectivity, dose-dependent sleep effects and safety in central nervous system (CNS), ...