Suvorexant for Opioid Use Disorder

Overseen By Justin Strickland, PhD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Johns Hopkins University

Disqualifiers: Pregnant, Breastfeeding, Seeking opioid treatment, others

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

Compensation: Varies

Number of Visits: Unknown

75 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether suvorexant (also known as Belsomra or MK-4305) can help individuals with Opioid Use Disorder (OUD) reduce their opioid and other drug use and cravings. Participants will receive either suvorexant or a placebo (a pill with no active medicine) to determine any differences in drug use and cravings. Eligible participants should have a diagnosis of moderate or severe OUD and not be currently seeking treatment. This research aims to discover new ways to support individuals in managing substance use issues. As an Early Phase 1 trial, the study focuses on understanding how suvorexant affects people with OUD, offering participants a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team to understand how your medications might interact with the trial.

Is there any evidence suggesting that suvorexant is likely to be safe for humans?

Research shows that suvorexant is generally well-tolerated. Some studies have examined its use for sleep problems in people with opioid use disorder (OUD), suggesting that suvorexant can improve sleep without major side effects. Animal studies showed no signs of withdrawal issues when stopping suvorexant suddenly.

While these findings are encouraging, the current trial remains in the early stages, so researchers are still carefully checking the treatment's safety. The FDA has already approved suvorexant for treating insomnia, which provides some reassurance about its safety. However, its effects in people with OUD are still under investigation. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for opioid use disorder?

Researchers are excited about Suvorexant for opioid use disorder because it works differently than traditional treatments like methadone or buprenorphine. Most treatments target opioid receptors to reduce cravings and withdrawal symptoms, but Suvorexant acts on the orexin system, which is involved in regulating sleep and wakefulness. This unique mechanism could potentially address sleep disturbances often experienced during opioid withdrawal, offering a novel approach to managing the disorder.

What evidence suggests that suvorexant might be an effective treatment for opioid use disorder?

Research has shown that suvorexant, initially used to treat insomnia, might aid individuals with opioid use disorder (OUD) by enhancing their sleep. Some studies found that suvorexant can extend sleep duration during opioid withdrawal. In this trial, participants will receive either suvorexant or a placebo to assess its potential in reducing cravings and stress associated with OUD. Although further research is necessary, these early findings suggest suvorexant could help manage symptoms related to opioid withdrawal. ^{1 2 3 5 6}

Who Is on the Research Team?

Justin Strickland, PhD

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 with moderate to severe Opioid Use Disorder, as defined by the DSM-5. Participants must have a history of substance use (details blinded), be in good health overall, and pass medical screenings including urine and blood tests. Those seeking opioid treatment, pregnant or breastfeeding individuals, or those with significant mental/physical disorders that could affect participation are excluded.

Inclusion Criteria

Meets Diagnostic and Statistical Manual-5 criteria for Opioid Use Disorder (OUD) (moderate or severe)

Lifetime substance use history criterion [blinded]

I am approved to take suvorexant and study medications.

Exclusion Criteria

Pregnant or breast feeding

Seeking opioid use treatment

Significant mental health or physical disorder that is expected to interfere with study participation as assessed by the study physicians or medical staff

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 visit

Inpatient Stay

Participants undergo a 14 to 16 day inpatient stay where they are stabilized on hydromorphone and randomly assigned to receive either suvorexant or placebo. They complete 5 experimental sessions with blinded study medications.

2 weeks

Daily monitoring and experimental sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Suvorexant

Trial Overview The study aims to see if suvorexant (20mg/day) can reduce usage, enjoyment, and craving for opioids compared to other undisclosed drugs (Drug A-D) and a placebo. The effectiveness of suvorexant against these blinded drugs will help understand its potential as a treatment option.

How Is the Trial Designed?

Group I: Suvorexant (20mg/day) Experimental Treatment 5 Interventions

Double blind administration of suvorexant once per day during residential stay until discharge

Group II: Placebo Placebo Group 5 Interventions

Double blind administration of placebo once per day during residential stay until discharge

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?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

Suvorexant, a dual orexin receptor antagonist used for treating insomnia, promotes sleep by blocking orexin receptors, and has been available since 2014 in the USA and Japan.

This report presents the first quantitation of suvorexant in postmortem specimens from three autopsy cases, indicating its potential relevance in forensic toxicology as its use may increase.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tissue Distribution of Suvorexant in Three Forensic Autopsy Cases. Waters, B., Hara, K., Ikematsu, N., et al.[2018]

Suvorexant, a dual orexin receptor antagonist approved for insomnia, is primarily metabolized in the body with 90% of its radioactivity recovered after administration, indicating effective absorption and elimination.

The drug mainly inhibits CYP3A4 and CYP2C19 enzymes but is unlikely to cause significant drug interactions at clinical doses due to low plasma concentrations, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro and in vivo characterisation of the metabolism and disposition of suvorexant in humans. Cui, D., Cabalu, T., Yee, KL., et al.[2017]

Suvorexant, a dual orexin receptor antagonist approved for insomnia, showed low potential for abuse in nonclinical studies, including tests for physical dependence and reinforcing efficacy in animal models.

The absence of significant withdrawal symptoms and lack of behavioral reinforcement in studies suggest that suvorexant is unlikely to be abused in humans, leading to its classification as a Schedule IV controlled substance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical assessment of the abuse potential of the orexin receptor antagonist, suvorexant. Born, S., Gauvin, DV., Mukherjee, S., et al.[2018]

In a study involving 38 participants with opioid use disorder, the dual-orexin receptor antagonist suvorexant improved total sleep time during a buprenorphine/naloxone taper, suggesting it may help with sleep disturbances associated with opioid withdrawal.

Participants receiving suvorexant showed decreased opioid withdrawal symptoms during the post-taper period, indicating its potential efficacy in managing withdrawal effects without increasing the risk of abuse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Suvorexant ameliorated sleep disturbance, opioid withdrawal, and craving during a buprenorphine taper. Huhn, AS., Finan, PH., Gamaldo, CE., et al.[2022]

Suvorexant, a drug that blocks orexin receptors and is typically used for insomnia, shows potential in reducing oxycodone-seeking behavior in rats, particularly after a period of withdrawal, suggesting it could be repurposed for treating prescription opioid use disorder (OUD).

While suvorexant did not significantly reduce overall oxycodone self-administration, it effectively decreased drug-seeking behavior during the first hour of testing and blocked reinstatement of seeking behavior, especially in male rats, indicating its potential efficacy in managing cravings associated with OUD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Suvorexant, an FDA-approved dual orexin receptor antagonist, reduces oxycodone self-administration and conditioned reinstatement in male and female rats. Illenberger, JM., Flores-Ramirez, FJ., Matzeu, A., et al.[2023]

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. clinicaltrials.gov clinicaltrials.gov/study/NCT06655883

NCT06655883 | A Study of Suvorexant (MK-4305) for the ... Researchers want to know if suvorexant will help people with OUD fall asleep and stay asleep. The goal of this study is to learn about the safety of suvorexant ...

2. reporter.nih.gov reporter.nih.gov/project-details/10454583

Evaluating Suvorexant for Sleep Disturbance in Opioid Use ... We hypothesize SUVO will improve total sleep time during withdrawal, will not show evidence of abuse liability, and will be more efficacious than trazodone.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7265392/

Repurposing the dual orexin receptor antagonist suvorexant ... Several clinical trials are currently underway to examine the efficacy of suvorexant in normalizing sleep outcomes, as well as craving, stress, and sleep ...

4. hopkinsmedicine.org hopkinsmedicine.org/news/articles/2024/12/improving-sleep-for-those-with-opioid-use-disorder

Improving Sleep for Those with Opioid Use Disorder Finding that suvorexant is safe and effective for the treatment of insomnia in people with OUD could spur the Food and Drug Administration ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0306453025002938

Effects of Suvorexant on Diurnal Cortisol and Patient ... The results demonstrated that total daily cortisol levels decreased during the buprenorphine taper across medication groups and were ...

6. science.org science.org/doi/10.1126/scitranslmed.abn8238

Suvorexant ameliorated sleep disturbance, opioid ... The results suggest that suvorexant might be a promising treatment for sleep and opioid withdrawal in individuals undergoing a buprenorphine/naloxone taper.