Suvorexant for Stimulant Use Disorder

Overseen By Jessica Vincent

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: The University of Texas Health Science Center, Houston

Must not be taking: MAO inhibitors, anticonvulsants

Disqualifiers: Opioid use disorder, severe diseases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: 12 days

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how suvorexant (also known as Belsomra) can aid individuals trying to stop using stimulants like cocaine or methamphetamine. The study examines whether suvorexant improves sleep, reduces stress, and curbs cravings during the early days of quitting. It also investigates if it helps individuals remain longer in residential treatment programs. Individuals with a stimulant use disorder who are fluent in English might be suitable for this trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

If you are currently taking medications that interact with suvorexant, such as MAO inhibitors, anticonvulsants, haloperidol, phenothiazines, anesthetics, or any sedatives, you will need to stop taking them to participate in the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that suvorexant is generally well-tolerated. The most common side effect is daytime sleepiness. In a large study, about 69% of participants taking suvorexant experienced some side effects, but only 5% faced serious issues. In comparison, 64% of those taking a placebo (a sugar pill) also reported side effects, with 7% experiencing serious problems. This suggests that suvorexant is relatively safe, with only a slightly higher rate of mild side effects compared to the placebo. ^{1 2 3 4 5}

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

Suvorexant is unique because it targets orexin receptors in the brain, which are involved in regulating wakefulness and sleep. Unlike traditional treatments for stimulant use disorder, which often focus on managing withdrawal symptoms or reducing cravings through neurotransmitter modulation, Suvorexant offers a novel approach by potentially improving sleep patterns and reducing nighttime cravings. Researchers are excited about this treatment because it could address the sleep disturbances commonly experienced by individuals with stimulant use disorder, offering a dual benefit of better sleep and possibly reduced stimulant use.

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

Research has shown that suvorexant, which participants in this trial may receive, can improve sleep. Studies have found that it helps people fall asleep and stay asleep better than a placebo. In individuals with mental health conditions, suvorexant increased total sleep time and reduced the time spent awake after falling asleep. It also lowered the risk of confusion (delirium) in older adults. While this trial continues to study its use for treating stimulant addiction, its ability to improve sleep might help reduce stress and cravings during early recovery. ^{1 3 6 7 8}

Who Is on the Research Team?

Heather Webber, PhD

Principal Investigator

The University of Texas Health Science Center, Houston

Are You a Good Fit for This Trial?

This trial is for individuals with Stimulant Use Disorder who are in the early stages of abstinence. The study aims to include those who could benefit from improved sleep and reduced drug cravings. Specific eligibility criteria details were not provided, so it's unclear what specific conditions would exclude someone.

Inclusion Criteria

Meet DSM-5 criteria for primary stimulant use disorder (either cocaine or methamphetamine)

Be fluent in English and able to understand the consent form

Exclusion Criteria

Head injury with loss of consciousness in the last 5 years

I have a history of seizures.

Undergoing medication-assisted treatment for withdrawal of any substance

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive suvorexant (SUVO) or treatment as usual (TAU) to assess effects on sleep, stress, and drug craving during early abstinence from stimulants

12 days

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of stress, sleep, and drug craving

2-4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Suvorexant

Trial Overview The study is testing the effects of suvorexant (SUVO), a medication that may help with sleep and stress, against treatment as usual (TAU) during early recovery from stimulants. It also looks at how these treatments affect length of stay and completion rates in a residential program after initial treatment.

How Is the Trial Designed?

Group I: SUVO Experimental Treatment 2 Interventions

Group II: TAU Active Control 1 Intervention

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?

The University of Texas Health Science Center, Houston

Lead Sponsor

Trials

974

Recruited

361,000+

Published Research Related to This Trial

The metabotropic glutamate 5 (mGlu5) receptor is essential for cocaine-induced synaptic plasticity in dopaminergic cells of the ventral tegmental area (VTA), as shown in a study using a genetic mouse model.

While mGlu5-deficient mice do not exhibit the enhanced synaptic response to cocaine, they still develop sensitized psychomotor responses, indicating that mGlu5 receptors are not necessary for all aspects of addiction, such as behavioral sensitization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cocaine-mediated synaptic potentiation is absent in VTA neurons from mGlu5-deficient mice. Bird, MK., Reid, CA., Chen, F., et al.[2016]

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]

Basimglurant is a novel mGlu5 negative allosteric modulator showing promising antidepressant-like properties in preclinical studies, with a favorable pharmacological profile that supports its potential use in treating major depressive disorder (MDD).

The drug demonstrates good oral bioavailability, a long half-life for once-daily dosing, and has shown effects on anxiety and pain, suggesting it may also help with common comorbidities associated with MDD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacology of basimglurant (RO4917523, RG7090), a unique metabotropic glutamate receptor 5 negative allosteric modulator in clinical development for depression. Lindemann, L., Porter, RH., Scharf, SH., et al.[2015]

Group II metabotropic glutamate receptors (mGlu(2/3)) play a crucial role in regulating dopamine and glutamate release in brain circuits associated with reward and drug seeking, and their function is impaired after prolonged drug use.

Pre-clinical studies suggest that mGlu(2/3) receptor agonists can reduce the rewarding effects of drugs and inhibit relapse behaviors, indicating their potential as a new therapeutic target for preventing relapse in drug addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Group II metabotropic glutamate receptors (mGlu2/3) in drug addiction. Moussawi, K., Kalivas, PW.[2021]

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]

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]

The optimization of the M5 NAM ML375 led to the development of a new compound, (S)-11 (VU6008667), which has a significantly shorter elimination half-life of 2.3 hours in rats, making it more suitable for addiction studies.

VU6008667 maintains comparable potency to ML375 while demonstrating high central nervous system penetration and excellent selectivity against other receptor types (M1-4), indicating its potential as a valuable tool in addiction research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Continued optimization of the M5 NAM ML375: Discovery of VU6008667, an M5 NAM with high CNS penetration and a desired short half-life in rat for addiction studies. McGowan, KM., Nance, KD., Cho, HP., et al.[2020]

Infusing the mGluR5 negative allosteric modulator MTEP into the nucleus accumbens core significantly reduced cocaine-seeking behavior during both context-induced relapse and cue-primed reinstatement tests, suggesting its potential as a therapeutic target for cocaine addiction.

In contrast, blocking mGluR5 in the dorsolateral striatum did not affect cocaine-seeking but impaired extinction learning, indicating that while mGluR5 in the NA core is crucial for regulating drug-seeking, its role in the dSTR is more related to learning processes rather than relapse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of ventral and dorsal striatum mGluR5 in relapse to cocaine-seeking and extinction learning. Knackstedt, LA., Trantham-Davidson, HL., Schwendt, M.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06655883

NCT06655883 | A Study of Suvorexant (MK-4305) for the ... People with opioid use disorder (OUD) can have trouble falling or staying asleep. Researchers want to know if suvorexant will help people with OUD fall ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7292311/

Suvorexant for insomnia in patients with psychiatric disorder The primary outcome of the study was the improvement in TST using self‐reported sleep diary. Other efficacy outcomes were improvements in TSO, wake time after ...

3. 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).

4. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2822422

Suvorexant for Reduction of Delirium in Older Adults After ... Findings In this randomized clinical trial of 203 participants, 17% in the suvorexant-treated group had delirium vs 26% in the placebo group; ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4772996/

Suvorexant: a promising, novel treatment for insomnia - PMC Results showed that all doses of suvorexant effectively promoted sleep compared to placebo, with no significant effects on PSG sleep parameters ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4591519/

Suvorexant in insomnia: efficacy, safety and place in therapy In general, suvorexant is well tolerated, with somnolence reported as the most significant adverse effect. Suvorexant is an exciting new option for the ...

7. thelancet.com thelancet.com/journals/laneur/article/PIIS1474-4422(14)70053-5/abstract

Safety and efficacy of suvorexant during 1-year treatment ... Serious adverse events were recorded in 27 patients (5%) who received suvorexant and 17 (7%) who received placebo. The most common adverse event ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1474442214700535

Safety and efficacy of suvorexant during 1-year treatment ... Over 1 year, 362 (69%) of 521 patients treated with suvorexant experienced any adverse events compared with 164 (64%) of 258 treated with placebo. Serious ...