Clinical trial NCT06104280: Medications for Opioid Use Disorder Photosensitive Retinal Ganglion Cell Function, Sleep, and Circadian Rhythms: Implications for Treatment
Official title: Medications for Opioid Use Disorder Differentially Modulate Intrinsically Photosensitive Retinal Ganglion Cell Function, Sleep, and Circadian Rhythms: Implications for Treatment (MOUD)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Opioid Use Disorder
Sleep Disturbance
Keywords: opioid use disorder
sleep
circadian rhythms
sleep disruption
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2023-10-27
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

Detailed description: Three medications for OUD (MOUD) are FDA-approved and regularly used to treat OUD: methadone, buprenorphine, and extended-release naltrexone (XR-NTX). However, persons who use opioids, including those prescribed MOUDs, report sleep disruption. In addition to the sleep centers of the brain, mu opioid receptors (MORs) are also expressed in the retina (including the human retina), specifically in ganglion cells that are critically important for non-image forming photoreception including circadian regulation of sleep-wake behavior. Pre-clinical studies show that activation of MORs on these intrinsically photosensitive retinal ganglion cells (ipRGCs) reduces the electrophysiological response to light, impacting critical ipRGC functions such as synchronization of sleep-wake behavior and circadian rhythms to light (photoentrainment), light-induced melatonin suppression, and the post-illumination pupillary reflex (PIPR). Together, these results suggest that activation of MORs in the ipRGCs by opioid use and/or MOUDs may impair downstream ipRGC functions. This multi-disciplinary study will examine the novel overarching hypothesis that persistent alterations in sleep/wake behavior in OUD patients undergoing treatment are mediated by impaired ipRGC function, and biomarkers of this pathway can predict recovery and relapse. Three aims will be tested in a sample of 200 participants, 150 of whom will be engaged in MOUD therapy (e.g., 50 each on methadone, buprenorphine, and XR-NTX, respectively) and 50 of whom will be non-opioid using control participants. Aim 1 will test the hypothesis that MOUD differentially impacts function of ipRGC responses. Aim 2 will examine whether MOUD differentially impacts daytime sleepiness, daily sleep-wake behavior, sleep architecture, and sleep-disordered breathing. Finally, Aim 3 will determine if ipRGC function predicts opioid relapse among MOUD groups at 1-, 3- and 6- month follow-up. Compared to non-opioid using controls or persons receiving an opioid antagonist (XR-NTX), we predict that participants who are receiving an agonist (methadone) or partial-agonist (buprenorphine) MOUD will have the most ipRGC interference, as evidenced by reduced PIPR, attenuated light-induced melatonin suppression, reduced circadian rhythmic amplitude, increased sleep latency, and increased sleep fragmentation. Importantly, we hypothesize that impaired ipRGC function will predict worse treatment outcomes as indicated by opioid use by 6-month follow-up. Finally, an exploratory aim will examine whether the MOUD groups show different relationships between opioid craving/withdrawal symptoms and sleep-wake behavior over a 10-day assessment of the participants' daily lives within the normal environment. The results of this study will be highly significant because it would support the use of the pupillary response to light and other indicators of ipRGC function as novel biomarkers to predict the response and outcomes to MOUDs.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

1. 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;
2. acutely suicidal, manic, intoxicated, or otherwise not stable enough to provide informed consent
3. self-reported use of illicit opioids, stimulants (prescribed or illicit), or benzodiazepines/sedative/hypnotics in the past month
4. alcohol or cannabis use disorder measured as severe on The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) Checklist
5. positive on UDS for illicit opioids (e.g., morphine, oxycodone, fentanyl),stimulants, benzodiazepines/sedative/hypnotics
6. 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)
7. persons diagnosed with narcolepsy

Primary outcomes:
measure: Aim 1: Post-Illumination Pupillary Response (PIPR)
timeFrame: 45 minutes
measure: Aim 2: Polysomnography
timeFrame: 2 night PSG
measure: Aim 3: Number of Participants Multiple Sleep Latency Test
timeFrame: 2 night PSG
measure: Aim 4: Number of Participants with Relapse
timeFrame: 6-month follow up
Secondary outcomes:
measure: Dim Light Melatonin Onset (DLMO)
timeFrame: 12 hours
measure: Melatonin suppression test
timeFrame: 12 hours
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
Study officials:
affiliation: University of Alabama at Birmingham
name: Karen Cropsey, PsyD
role: PRINCIPAL_INVESTIGATOR
References: