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

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

Interventions

OTHER

Post-Illumination Pupillary Response (PIPR)

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

OTHER

Polysomnography

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

OTHER

Multiple Sleep Latency Test

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

BEHAVIORAL

Ecological Momentary Assessments

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.

DEVICE

Actigraphy

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

OTHER

DLMO

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.

OTHER

Melatonin Suppression Test

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

Sponsors & Collaborators

• National Institute on Drug Abuse (NIDA)

  collaborator NIH

• University of Alabama at Birmingham

  lead OTHER

Principal Investigators

• Karen Cropsey, PsyD · University of Alabama at Birmingham

Eligibility

Min Age

18 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2025-01-06

Primary Completion

2028-12-28

Completion

2029-01-01

FDA Device

Yes

Countries

• United States

Study Locations