Sleep and Circadian Rhythm Assessments for Opioid Use Disorder

(MOUD Trial)

Overseen By Brionna Smith, B.S.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Alabama at Birmingham

Must be taking: Methadone, XR-NTX, Buprenorphine

Must not be taking: Illicit opioids, Stimulants, Benzodiazepines

Disqualifiers: Eye disease, Suicidal, Narcolepsy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand why individuals with opioid use disorder (OUD) often struggle with sleep, even when taking medications like methadone, buprenorphine, or naltrexone. Researchers will examine how certain eye neurons that respond to light might affect sleep patterns in these individuals. Participants will undergo tests such as the Multiple Sleep Latency Test (a measure of daytime sleepiness), Polysomnography (a comprehensive sleep study), and Post-Illumination Pupillary Response (PIPR, a test of eye response to light). Those who have been on stable medication for OUD for at least a month and have no major eye issues might be suitable candidates. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could improve sleep health for those with OUD.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must be stable on your medication for opioid use disorder (no dose change) for the past month to participate.

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

Research shows that the treatments used in this study—methadone, buprenorphine, and extended-release naltrexone—are generally well-tolerated by people with opioid use disorder (OUD).

Methadone has been extensively studied and is known to affect sleep patterns, but it is considered safe for treating OUD. Sleep issues can occur, but they are usually manageable.

Buprenorphine may increase alertness and alter sleep stages, but many report overall sleep improvement when using it as part of their OUD treatment. This indicates it is generally well-tolerated, despite some sleep-related side effects.

Extended-release naltrexone is another treatment option for OUD. While detailed information on its effects on sleep is limited, it is an approved treatment for opioid dependency, indicating a recognized safety profile.

Overall, these medications have been used to treat OUD and have established safety records. Sleep-related side effects can occur, but they are usually not serious enough to outweigh the treatment benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores how sleep and circadian rhythms may be linked to opioid use disorder and its treatment. Unlike traditional methods focusing solely on medication, this trial uses advanced techniques like the Multiple Sleep Latency Test and Polysomnography to assess sleep patterns, and the Post-Illumination Pupillary Response to study how the eyes react to light. These methods could uncover how sleep disturbances affect individuals with opioid use disorder, which might lead to new, holistic approaches for treatment. This trial could pave the way for integrating sleep health into addiction treatment, potentially improving outcomes for those undergoing medication-assisted therapies like methadone, buprenorphine, or extended-release naltrexone.

What evidence suggests that this trial's treatments could be effective for sleep disturbances in opioid use disorder?

This trial will compare different medication-assisted treatments for opioid use disorder (OUD) and their effects on sleep and circadian rhythms. Research has shown that people with OUD often experience sleep problems and disruptions in their natural sleep-wake cycle, even while receiving medication-assisted treatments. Participants in this trial may receive methadone, buprenorphine, or extended-release naltrexone. Studies have found that methadone and buprenorphine users frequently experience disrupted sleep, affecting recovery and increasing relapse risk. Methadone users, in particular, show less responsiveness in their natural sleep-wake cycle, impacting sleep patterns. Buprenorphine is linked to severe sleep disruptions, worsening cravings and increasing relapse chances. While extended-release naltrexone helps treat OUD, sleep problems can still occur, especially during withdrawal and treatment. This research explores how certain light-sensitive cells in the eye might contribute to these sleep issues, potentially leading to better treatment outcomes. ^{3 6 7 8 9}

Who Is on the Research Team?

Karen Cropsey, Psy.D.

Principal Investigator

University of Alabama at Birmingham

Are You a Good Fit for This Trial?

This trial is for adults over 18 who are on stable doses of FDA-approved medications for opioid use disorder, such as methadone, XR-NTX, or buprenorphine. Participants must have a positive drug screen if prescribed these medications but cannot be using illicit opioids or other drugs like stimulants and benzodiazepines.

Inclusion Criteria

My drug screen was positive for buprenorphine or methadone, which were prescribed to me.

I am taking medication for opioid addiction or I am a healthy control.

Stable on MOUD (no dose change) for the past month

Exclusion Criteria

You have used illegal drugs or certain prescription drugs in the past month.

You have a severe alcohol or cannabis use problem, as determined by a checklist used by doctors.

I have a history of or currently have an eye condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive MOUD therapy with methadone, buprenorphine, or extended-release naltrexone, and undergo assessments of ipRGC function, sleep, and circadian rhythms

6 months

Multiple visits for assessments and follow-ups

Follow-up

Participants are monitored for relapse and treatment outcomes, including self-reported drug cravings and withdrawal symptoms

6 months

Exploratory Assessment

10-day assessment of daily sleep-wake behavior and opioid craving/withdrawal symptoms in participants' normal environment

10 days

What Are the Treatments Tested in This Trial?

Interventions

• Multiple Sleep Latency Test
• Polysomnography
• Post-Illumination Pupillary Response (PIPR)

Trial Overview The study examines how certain neurons in the retina might affect sleep and circadian rhythms in people with opioid use disorder. It involves tests like sleep latency measurement, pupil response tracking after light exposure, momentary assessments during daily life activities, overnight sleep monitoring (polysomnography), melatonin suppression testing, activity tracking (actigraphy), and timing of melatonin onset in saliva (DLMO).

How Is the Trial Designed?

Group I: Non-opioid using controls Experimental Treatment 7 Interventions

non-opioid using controls

Group II: MOUD therapy methadone Experimental Treatment 7 Interventions

50 methadone participants

Group III: MOUD therapy extended-release naltrexone Experimental Treatment 7 Interventions

50 extended-release naltrexone (XR-NTX) participants

Group IV: MOUD therapy buprenorphine Experimental Treatment 7 Interventions

50 buprenorphine participants

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

In a study of 37 opioid-dependent participants receiving either methadone or buprenorphine, sleep duration and timing were significantly affected by drug use, with illicit opioid use leading to less sleep and later bedtimes.

The clinic hours for opioid agonist treatment (OAT) also influenced sleep patterns, as participants reported sleeping less and waking earlier when attending early morning clinic hours, indicating that clinic schedules can impact the sleep/wake cycles of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sleep reductions associated with illicit opioid use and clinic-hour changes during opioid agonist treatment for opioid dependence: Measurement by electronic diary and actigraphy. Bertz, JW., Epstein, DH., Reamer, D., et al.[2021]

A pilot study involving 8 male participants demonstrated that a wireless sleep EEG monitor (Sleep Profiler™) is a feasible tool for objectively measuring sleep outcomes during opioid withdrawal, with participants using it 85.6% of scheduled nights.

The wireless EEG provided more detailed insights into sleep architecture compared to self-reported sleep diaries, revealing significant associations between sleep quality and withdrawal severity, which could inform future treatment interventions for sleep issues in opioid use disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Wireless electroencephalography (EEG) to monitor sleep among patients being withdrawn from opioids: Evidence of feasibility and utility. Dunn, KE., Finan, PH., Huhn, AS., et al.[2023]

Citations

1. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2829838

Rest-Activity Rhythms, Their Modulators, and Brain-Clinical ... This cross-sectional study investigates brain state dynamics and rest-activity rhythms, including sleep, physical activity, and circadian ...

2. reporter.nih.gov reporter.nih.gov/search/14E9CE024F8FC5D27598B8961CAA4A01A2FFCEB861BF/project-details/11171667

Sleep and circadian rhythm phenotypes and mechanisms ... Findings from this project will enhance our understanding of specific sleep and circadian rhythms parameters implicated in OUD, and the relationships among ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06104280

Medications for Opioid Use Disorder Photosensitive ... In this project, we will investigate a special set of photosensitive neurons in the retina as an underlying mechanism for circadian rhythm and sleep disturbance ...

4. academic.oup.com academic.oup.com/sleep/article/46/Supplement_1/A304/7182370

0693 Rest-activity rhythm in Methadone and Buprenorphine ... In OUD, sleep and circadian disruptions are highly prevalent, interfere with retention in opioid maintenance treatment (OMT) and increase ...

5. nature.com nature.com/articles/s41380-023-02241-6

Circadian rhythm disruptions associated with opioid use ... Opioid craving and relapse vulnerability is associated with severe and persistent sleep and circadian rhythm disruptions.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3197808/

Buprenorphine Disrupts Sleep and Decreases Adenosine ... Buprenorphine significantly increased time spent awake, decreased nonrapid eye movement sleep, and increased latency to sleep onset.

7. withpower.com withpower.com/trial/phase-dyssomnias-2024-29c39

Sleep and Circadian Rhythm Assessments for Opioid Use ... The studies reviewed focus on sleep monitoring and treatments for opioid use disorder, but they do not provide specific safety data for the sleep and circadian ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5270620/

Self-reported Sleep Improvement in Buprenorphine MAT ... Findings suggest that subjects reported improvement in both sleep and depression after initiating MAT with buprenorphine/naloxone.

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1389945719302254

Opioids and sleep – a review of literature Various studies on opioid sleep pattern suggest that they disrupt normal sleep architecture, disturbance ranges from 30 to 80%.