Lemborexant for insomnia in adults with opioid use disorder on buprenorphine

Neurofunctional Phenotyping to Investigate the Role of the Orexin System at the Intersection of Opioid Use Disorder and Insomnia Among Women and Men Receiving Buprenorphine

This trial will see if taking lemborexant each night for 8 weeks improves sleep, mood, and impulsive behavior in adults with moderate opioid use disorder who are stable on buprenorphine.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Virginia Commonwealth University (Academic / other)
• Locations: 1 site (Richmond, Virginia)
• Trial ID: NCT06981195 on ClinicalTrials.gov

What this trial studies

This Phase 2 interventional trial compares nightly lemborexant 10 mg to placebo over 8 weeks in adults with opioid use disorder who are receiving stable outpatient buprenorphine treatment. Participants are assigned to active drug or placebo and complete measures of sleep, computerized tests of impulsive behavior, and mood/behavior assessments across 23 study visits. Most visits are short check-ins, with a longer screening visit; urine and breath/toxicology screens are used to confirm eligibility. The goal is to determine whether lemborexant produces greater improvement than placebo on sleep and related mood and behavioral outcomes in this population.

Who should consider this trial

Good fit: Adults 18 and older with at least moderate DSM-5 opioid use disorder who are stabilized for at least 4 weeks on sublingual (8–24 mg) or extended‑release injectable buprenorphine, screen positive for chronic insomnia with an Insomnia Severity Index ≥13, and have negative urine toxicology for non‑prescribed substances (except cannabinoids).

Not a fit: People not on stable buprenorphine, those without clinically significant insomnia (ISI <13), individuals with unstable medical or psychiatric conditions, or those who cannot pass required toxicology/alcohol screens are unlikely to qualify or benefit from this study.

Why it matters

Potential benefit: If successful, lemborexant could improve sleep and reduce mood and impulsivity problems for people with opioid use disorder on buprenorphine, potentially making insomnia easier to manage in this group.

How similar studies have performed: Orexin receptor antagonists like lemborexant have shown effectiveness for insomnia in general populations, but their use specifically in people with opioid use disorder is novel and less well studied.

Eligibility criteria

Inclusion Criteria:

1. Be 18 + years-of-age
2. Meet current DSM-5 criteria for opioid use disorder (OUD) with at least moderate severity
3. Receiving outpatient treatment for OUD with sublingual buprenorphine film/tablets ranging 8mg to 24mg or with extended-release injectable buprenorphine
4. Stabilized on current buprenorphine dosage for at least 4 weeks without intention for dose change within next 3 months.
5. Screening urine toxicology positive for buprenorphine and an appropriate norbuprenorphine level as determined by a study clinician
6. A screening urine toxicology negative for non-prescribed substances (except cannabinoids) with a negative breath (or oral fluid) alcohol screen
7. Screen positive for chronic insomnia on the Insomnia Symptom Questionnaire (ISQ)
8. Have an Insomnia Severity Index score at screening and baseline of 13 or higher
9. Have no clinically significant medical or psychiatric disorder or condition, based on physical exam and medical history performed by study clinician, that in the judgement of the investigator would prevent participation or heighten safety risks
10. Understand the study procedures and provide written informed consent in English language
11. Access to necessary resources for completing virtual surveys and monitoring (i.e., computer or smartphone, internet or cell service)

Exclusion Criteria:

1. Current diagnosis of sleep-related breathing disorder, narcolepsy, somnambulism, or sleep paralysis
2. A positive screen for sleep apnea by the following: Sleep Disorders Screening Battery (STOP-BAG \>5) OR home sleep apnea test using WatchPAT with Apnea Hypopnea Index (AHI) with 3% drop in oxygen saturation \> 10 OR \>50% of respiratory events being central if AHI is between 5-10 OR Oxygen Desaturation \< 88% for \> 10 minutes, OR oxygen desaturation index (ODI) using 3% drop in oxygen saturation \> 10
3. Currently receiving treatment for insomnia (behavioral or pharmacologic)
4. Currently taking a medication to treat a sleep-related condition (e.g., zolpidem) or unable to discontinue over-the-counter drug or supplement used to treat sleep-related condition
5. Currently taking benzodiazepines or other CNS active medications that may increase risk to the participant, per PI discretion (e.g., opioids other than buprenorphine, antipsychotics)
6. Current DSM-5 diagnosis (any severity) of alcohol or drug use disorder (e.g., benzodiazepine, stimulant) with non-prescribed substance use within last 3 months; nicotine use disorder is not considered exclusionary
7. Cannabis use \> 3 days/week
8. Uncontrolled serious psychiatric disorder that would make study participation unsafe (such as Bipolar I Disorder, ADHD, Schizophrenia, schizoaffective disorders, major depressive disorder with psychotic features, or a neurological disorder).
9. Uncontrolled neurological, cardiovascular, or pulmonary medical condition such as seizure disorder, recent myocardial infarction, stroke, hospitalization for chronic obstructive pulmonary disease
10. Baseline ECG with clinically significant abnormal conduction or with QTc of greater than 450ms
11. Significant current suicidal or homicidal ideation (C-SSRS "yes" answers on questions 4 or 5) or a history of suicide attempt within the past 6 months
12. Any of the following lab abnormalities: ALT/AST 2 or more times the upper limit of normal, Total bilirubin 2 or more times the upper limit of normal, Creatinine 1.5 or more times the upper limit of normal
13. Pregnant or breastfeeding; Females who are having sex that includes penile penetration must be non-pregnant, non-lactating, and either be of non-childbearing potential (e.g., sterilized via hysterectomy, bilateral tubal ligation, or bilateral oophorectomy, or at least 1 year post-menopausal) or of childbearing potential, and agree to use an acceptable form of contraception (e.g., IUD, hormonal implant, hormonal patch/ring/pill, condoms (male or female), etc.)
14. Currently taking prescription or over-the counter drugs or dietary supplements known to significantly inhibit CYP3A4 (such as clarithromycin, telithromycin, nefazodone, itraconazole, ketoconazole, atazanavir, darunavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, tipranavir); or CYP3A4 inducers (such as phenobarbital, phenytoin, rifampicin, St. John's Wort, and glucocorticoids)
15. Currently taking lemborexant or any previous medically adverse reaction to lemborexant or other dual orexin receptor antagonists
16. Currently incarcerated or pending incarceration

Where this trial is running

Richmond, Virginia

• VCU Institute for Drug and Alcohol Studies — Richmond, Virginia, United States (Recruiting)

Study contacts

• Principal investigator: Caitlin E Martin, MD — Virginia Commonwealth University Institute for Drug and Alcohol Studies
• Study coordinator: Joyce Ruddley, RN

Conditions Opioid Use Disorder; Opioid Use; Insomnia; Orexin Antagonist; buprenorphine; lemborexant