Suvorexant for Opioid Use Disorder

No longer recruiting at 4 trial locations

Overseen By Andrew S Huhn, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Johns Hopkins University

Must be taking: Methadone, Buprenorphine, XR-NTX

Must not be taking: Benzodiazepines, Suvorexant, Stimulants, others

Disqualifiers: Serious mental illness, Stimulant use, Pregnancy, 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

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how the sleep medication suvorexant might aid people recovering from opioid use disorder (OUD) who experience sleep problems. Researchers aim to determine if improving sleep can reduce stress and prevent relapse in those taking medications like methadone, buprenorphine, or naltrexone for OUD. Participants will receive either suvorexant or a placebo (a pill with no active medication) to compare effects. Individuals who have abstained from illicit opioids for at least two weeks and are undergoing specific OUD treatments with sleep disturbances may be suitable for this study. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

You may need to stop taking certain medications to participate in this trial. Specifically, you cannot use benzodiazepines or other schedule IV medications for insomnia, Cytochrome P450 3A inhibitors, or glucocorticoid medications. If you are on these, you might need to stop them before joining the study.

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

Research shows that suvorexant is generally safe for people. In studies, suvorexant has improved sleep for those with opioid use disorder (OUD), particularly during opioid withdrawal. Other research on opioids has found no withdrawal issues when stopping suvorexant suddenly, suggesting it might not be addictive or cause dependence.

Some studies have also found that suvorexant can help with both sleep problems and symptoms of opioid withdrawal. This dual benefit could be very helpful for people receiving medication-assisted treatment (MAT) for OUD. However, like any medication, it can have side effects. Overall, the research so far suggests that suvorexant is well-tolerated and does not raise major safety concerns. ^{1 2 3 4 5}

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

Most treatments for opioid use disorder focus on managing withdrawal symptoms and cravings using medications like methadone, buprenorphine, or naltrexone. But Suvorexant works differently, targeting the sleep disturbances that often accompany addiction recovery. Researchers are excited about Suvorexant because it is an orexin receptor antagonist, which can help regulate sleep patterns without the addictive potential of traditional sleep aids. This unique mechanism of action gives it a distinct advantage, potentially improving both sleep and the overall recovery process for those battling opioid use disorder.

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

Research has shown that suvorexant, which participants in this trial may receive, might improve sleep for those recovering from opioid use disorder (OUD). Several studies are exploring its effectiveness for sleep problems related to opioid withdrawal. Early results suggest that suvorexant helps individuals fall asleep and stay asleep longer without signs of misuse. Some early evidence also indicates that suvorexant can reduce the urge to seek drugs in similar situations, making it a promising option for addressing sleep and stress issues in people with OUD. Participants in this trial may also receive a placebo as part of the study's design. ^{1 2 3 5 6}

Who Is on the Research Team?

Andrew S Huhn, PhD

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

This trial is for adults aged 21-65 with opioid use disorder who are in early recovery and experiencing sleep disturbances. They must be on medication-assisted treatments like methadone, buprenorphine, or XR-NTX, have abstained from illicit opioids for two weeks, and agree to weekly visits and daily monitoring. Exclusions include unstable serious mental illnesses, other severe substance disorders, certain medication allergies or uses, pregnancy/breastfeeding, specific sleep disorders like narcolepsy or severe apnea.

Inclusion Criteria

Have no clinically significant chronic medical disorders or conditions that are judged by the investigators to prevent participation.

Use of birth control throughout study

I am between 21 and 65 years old.

Exclusion Criteria

I am not taking steroids or medications that affect my hormone control system.

I have been diagnosed with narcolepsy, sleep paralysis, or restless leg syndrome.

You have shown signs of wanting to harm yourself in the past month, as evaluated by a specific questionnaire.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either suvorexant or placebo while maintained on medication-assisted treatments (MAT) for opioid use disorder

8 weeks

Weekly visits for assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebos
• Suvorexant

Trial Overview The study tests whether suvorexant can improve sleep and reduce stress-related relapse behaviors in patients recovering from opioid addiction compared to a placebo. Participants maintained on different medications (methadone/buprenorphine/XR-NTX) will randomly receive either suvorexant or a placebo while their sleep patterns and stress levels are monitored.

How Is the Trial Designed?

Group I: Suvorexant Active Control 1 Intervention

Sleep medication (20mg suvorexant; 2 10mg capsules; patients can self-titrate to 1 10mg capsule)

Group II: Placebo Placebo Group 1 Intervention

Placebo sleep medication (2 placebo oral capsules)

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 Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

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, 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, 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]

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 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]

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/S0376871623001977

Preclinical Evidence Supporting the Repurposing of ... Suvorexant normalizes sleep disturbances associated with initial cocaine abstinence and facilitates the extinction of cocaine seeking behaviors.

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.