Medications for Opioid Use Disorder Photosensitive Retinal Ganglion Cell Function, Sleep, and Circadian Rhythms: Implications for Treatment

NCT06104280 | Recruiting DMC FDA Device

• 2 other identifiers: IRB-300011499R01DA059471-01
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 2

Brief Summary

Opioid use disorder (OUD) is a treatable medical illness with three medications FDA approved for treatment. However, persons with OUD report significant sleep disturbance, even when treated with medications for opioid use disorder, leading to high rates of relapse. 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 from opioid use and medications for OUD that could lead to novel intervention and improve treatment outcomes.

Conditions

Opioid Use Disorder; Sleep Disturbance

Keywords

opioid use disorder; sleep; circadian rhythms; sleep disruption

Outcome Measures

Primary Outcomes (4)

• Aim 1: Post-Illumination Pupillary Response (PIPR)

  10-day at home actigraphy and ecological momentary assessments (EMA period), participants will be scheduled for Visit 3. Upon arrival, the non-dominant eye is dilated with Tropicamide 0.5% and Phenylephrine 2.5% (this lower-than-normal dilation dosage will be effective for the duration of the experiment but will fully dissipate within \~6 hours). Subjects are then seated in a dimly lit room (\< 5 lux, background light) for 30 minute to dark adapt and to ensure complete pupil dilation prior to the study. The PIPR is measured in six, 80-second test periods in which the stimulus, either Blue (470 nm) or Red (623 nm), is presented to the dilated eye while the pupil response of the un-dilated eye is measured (consensual pupil response). During a test period, after an initial 20-second fixation period, the stimulus is presented for 1 second followed by a 60-second fixation period. The red stimulus primarily serves as a control for any nonspecific influences on the PIPR.

  45 minutes

• Aim 2: Polysomnography

  Polysomnography (PSG)110: To avoid potential first-night effects often observed with PSG, participants will undergo two consecutive nights of PSG, scheduled to begin according to their habitual sleep/wake times. PSG will be conducted in dedicated research rooms located at the University of Alabama at Birmingham Sleep/Wake Disorders Center at Highlands Hospital (refer to Sleep and Circadian Research Core LOS). Trained staff will attach electrodes to measure electroencephalography (EEG), electrooculography (EOG), electromyography (EMG), electrocardiography (ECG), respiratory channels (effort and nasal pressure), and oxygen saturation. The values of the EEG, EOG, EMG, ECG respiratory channels, and oxygen saturation will be combined to report a single PSG value.

  2 night PSG

• Aim 3: Number of Participants Multiple Sleep Latency Test

  On the morning following the second night of PSG, participants will undergo an MSLT following standardized guidelines. Briefly, the multiple sleep latency test (MSLT) consists of 5 nap opportunities that occur every two hours with the first nap beginning 1.5 to 3 hours after the end of the PSG (in this case, after the end of the 2nd night of PSG).

  2 night PSG

• Aim 4: Number of Participants with Relapse

  Self reported drug cravings, and self-reported withdrawal symptoms by 6-month follow up.Self-reported and urine drug screen confirmed drug use.

  6-month follow up

Secondary Outcomes (2)

• Dim Light Melatonin Onset (DLMO)

  12 hours

• Melatonin suppression test

  12 hours

Study Arms (4)

MOUD therapy methadone

50 methadone participants

Other: Post-Illumination Pupillary Response (PIPR); Other: Polysomnography; Other: Multiple Sleep Latency Test; Behavioral: Ecological Momentary Assessments; Device: Actigraphy; Other: DLMO; Other: Melatonin Suppression Test

MOUD therapy buprenorphine

50 buprenorphine participants

Other: Post-Illumination Pupillary Response (PIPR); Other: Polysomnography; Other: Multiple Sleep Latency Test; Behavioral: Ecological Momentary Assessments; Device: Actigraphy; Other: DLMO; Other: Melatonin Suppression Test

MOUD therapy extended-release naltrexone

50 extended-release naltrexone (XR-NTX) participants

Other: Post-Illumination Pupillary Response (PIPR); Other: Polysomnography; Other: Multiple Sleep Latency Test; Behavioral: Ecological Momentary Assessments; Device: Actigraphy; Other: DLMO; Other: Melatonin Suppression Test

Non-opioid using controls

non-opioid using controls

Other: Post-Illumination Pupillary Response (PIPR); Other: Polysomnography; Other: Multiple Sleep Latency Test; Behavioral: Ecological Momentary Assessments; Device: Actigraphy; Other: DLMO; Other: Melatonin Suppression Test

Interventions

Polysomnography OTHER

Measure electroencephalography (EEG), electrooculography (EOG), electromyography (EMG), electrocardiography (ECG), respiratory channels (effort and nasal pressure), and oxygen saturation.

Also known as: PSG

MOUD therapy buprenorphine; MOUD therapy extended-release naltrexone; MOUD therapy methadone; Non-opioid using controls

Multiple Sleep Latency Test OTHER

Assist in the diagnosis of disorders of hypersomnolence,63 it is also used in research to quantify daytime sleepiness and serves as a more objective measure of daytime sleepiness than self-report questionnaires

Also known as: MSLT

MOUD therapy buprenorphine; MOUD therapy extended-release naltrexone; MOUD therapy methadone; Non-opioid using controls

DLMO OTHER

Participants will be given an evening meal and then be accompanied to the UAB Highlands Hospital Sleep Unit by 5:30pm. The sleep unit allows for strict control of light exposure (\< 5 lux at eye level), room temperature and oral intake factors that could alter melatonin levels.Participants will be allowed to sleep in darkness until 8:00am, at which time they will be provided transportation.We will also bank frozen samples taken prior to the light exposure for later calculation of the Dim Light Melatonin Onset (DLMO), a circadian phase estimate.

Also known as: Dim Light Melatonin Onset

MOUD therapy buprenorphine; MOUD therapy extended-release naltrexone; MOUD therapy methadone; Non-opioid using controls

Post-Illumination Pupillary Response (PIPR) OTHER

The PIPR is measured in six, 80-s test periods in which the stimulus, either Blue (470 nm) or Red (623 nm), is presented to the dilated eye while the pupil response of the un-dilated eye is measured (consensual pupil response

Also known as: PIPR

MOUD therapy buprenorphine; MOUD therapy extended-release naltrexone; MOUD therapy methadone; Non-opioid using controls

Ecological Momentary Assessments BEHAVIORAL

Morning after overnight Visit 2, participants will complete ecological momentary assessments (EMAs) over a 10-day assessment period. Using EMA through the InsightTM mHealth platform to capture momentary craving, withdrawal and mood states across 10 days among persons who smoke and nonsmokers prior to an overnight procedures. Participants will complete morning and evening sleep diaries via the EMA InsightTM mHealth platform self-reported sleep and wake information, fatigue, naps, opioid craving and withdrawal.

Also known as: EMA

MOUD therapy buprenorphine; MOUD therapy extended-release naltrexone; MOUD therapy methadone; Non-opioid using controls

Actigraphy DEVICE

7-day actigraphy period will be used to determine the habitual sleep start and wake times. The CamNTech MotionWatch8 (Cambridge, UK) is a solid-state piezo-electric accelerometer that collects data on activity (i.e., arm motion) and ambient light.Actigraphy data are downloaded from the MotionWatch8 into the software (MotionWare) for analysis, management, and exportation. Bed and wake times will be entered by the subjects via a REDCap link and this information coupled with the sleep diary reports will be entered to determine sleep intervals. Algorithms in the Motion Watch 8 software will determine sleep start, sleep end, total sleep time (duration), sleep quality, sleep efficiency, wake after sleep onset, and sleep fragmentation

MOUD therapy buprenorphine; MOUD therapy extended-release naltrexone; MOUD therapy methadone; Non-opioid using controls

Melatonin Suppression Test OTHER

The sleep unit allows for strict control of light exposure (\< 5 lux at eye level), room temperature and oral intake factors that could alter melatonin levels. Participants will be asked to refrain from caffeine consumption 12 hours before reporting to the sleep unit and will provide 2-3 ml of saliva every 30 minutes starting at 6:00pm and ending after the light exposure. For melatonin suppression, 2-hours light exposure will begin 2 hours before the calculated mid-sleep time. Collection saliva samples 1-h, 30-min, and immediately before the light exposure and every 30 min throughout exposure. Samples will be centrifuged and frozen/stored at -20ºC until assay and remaining samples stored at -80ºC. Melatonin levels will be assayed via the Buhlmann Direct Saliva Melatonin. Melatonin suppression will be calculated as the percent decrease from the sample taken immediately prior to the light exposure

MOUD therapy buprenorphine; MOUD therapy extended-release naltrexone; MOUD therapy methadone; Non-opioid using controls

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This study involves people who are receiving one of three medications for opioid use disorder (methadone, buprenorphine or naltrexone) or healthy controls.

You may qualify if:

• Adults (18+)
• prescribed one of three medications for opioid use disorder (methadone, XR-NTX, buprenorphine) or healthy control
• stable on MOUD (no dose change) for the past month
• positive on urine drug screen (UDS) for buprenorphine or methadone if prescribed those medications

You may not qualify if:

• eye disease reported by history or noted on exam including disease of the anterior and posterior segment of the eye, cataracts, retinopathy, glaucoma, cataracts, amblyopia, scotoma, color or night blindness, corneal pathologies, macular degeneration, or retinitis pigmentosa;
• acutely suicidal, manic, intoxicated, or otherwise not stable enough to provide informed consent
• self-reported use of illicit opioids, stimulants (prescribed or illicit), or benzodiazepines/sedative/hypnotics in the past month
• alcohol or cannabis use disorder measured as severe on The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) Checklist
• positive on UDS for illicit opioids (e.g., morphine, oxycodone, fentanyl),stimulants, benzodiazepines/sedative/hypnotics
• shift workers who work outside normal 7 a.m. to 6 p.m. hours, according to the National Institute of Occupational Safety and Health (NIOSH)
• persons diagnosed with narcolepsy

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (2)

University of Alabama at Birmingham

Birmingham, Alabama, 35226, United States

NOT YET RECRUITING

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

RECRUITING

MeSH Terms

Conditions

Opioid-Related Disorders; Parasomnias

Interventions

Ecological Momentary Assessment; Actigraphy

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Sleep Wake Disorders; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Psychological Tests; Behavioral Disciplines and Activities; Monitoring, Physiologic; Diagnostic Techniques and Procedures; Diagnosis; Accelerometry; Investigative Techniques

Study Officials

• Karen Cropsey, PsyD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Karen Cropsey, PsyD

CONTACT

205-975-7809; kcropsey@uabmc.edu

Brionna Smith, B.S.

CONTACT

205-975-7809; cropseylab@uabmc.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 19, 2023
• First Posted: October 27, 2023
• Study Start: January 6, 2025
• Primary Completion (Estimated): December 28, 2028
• Study Completion (Estimated): January 1, 2029
• Last Updated: April 9, 2026

Record last verified: 2025-04

Locations

US (2)