Pupillary Unrest as an Indicator of Central Opioid Effect in Subjects 40-60 Years of Age

Study Overview
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Brief Summary
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This study will establish the relationship between magnitude of opioid exposure and a pupillary measure referred to as PUAL (pupillary unrest in ambient light), in subjects aged 40-60. Previous investigation demonstrated that loss of PUAL was a sensitive, discriminative indicator of opioid toxicity and respiratory depression among subjects aged 20-40 years old. Population data indicate that pupil size and PUAL decline slightly with age. The investigators will explore whether PUAL proves to be a sensitive indicator of opioid exposure and respiratory depression in this older group.

Detailed Description
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Healthy volunteer subjects aged 40-60 will receive a standardized weight-based 10-minute remifentanil infusion protocol to achieve a peak estimated remifentanil effect site concentration of approximately 6 ng/mL. Pupillary measures will be taken at baseline and regular time intervals during and after the infusion, over a period of 35 minutes.

Official Title
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Pupillary Unrest as an Indicator of Central Opioid Effect in Subjects 40-60 Years of Age

Conditions
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Opioid Toxicity, Pupillary Miosis, Respiratory Depression

Intervention / Treatment
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* Drug: Remifentanil Hydrochloride
* Device: Pupillometry measurement


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy, BMI < 35 kg/m2 Exclusion Criteria: current or recent opioid use opioid or other substance use disorder known or suspected OSA or sleep disordered breathing ischemic heart disease, heart failure or symptomatic arrhythmia history ocular disease or previous eye surgery active use of alpha adrenergic blockers, anticholinergic medications, active use of antidepressant or mood stabilizing medications active use of phosphodiesterase inhibitors use of stimulant or appetite suppressant medications active use of antihypertensive or antiarrhythmic medications use of topical eye medications.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Noninteractive, then Interactive<br>Participants undergo the infusion under noninteractive conditions, followed by a second drug infusion under interactive conditions. | Drug: Remifentanil Hydrochloride<br>* Infusion of 0.2 µg/k/m for 5 minutes, the 0.3 µg/k/m for 5 minutes. Pupillary measurements will be taken at baseline and every 2.5 minutes during the 10-minute infusion and 25-minute recovery period.<br>Device: Pupillometry measurement<br>* The pupil will be examined with the pupillometer at regular intervals, before during and after the opioid infusion<br>|
| Experimental: Interactive, then Noninteractive<br>Participants undergo the infusion under interactive conditions, followed by a second drug infusion under noninteractive conditions. | Drug: Remifentanil Hydrochloride<br>* Infusion of 0.2 µg/k/m for 5 minutes, the 0.3 µg/k/m for 5 minutes. Pupillary measurements will be taken at baseline and every 2.5 minutes during the 10-minute infusion and 25-minute recovery period.<br>Device: Pupillometry measurement<br>* The pupil will be examined with the pupillometer at regular intervals, before during and after the opioid infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Time Concentration Curve (AUC 0-35 minutes) | PUAL measured by pupillometer. | Baseline, and every 2.5 minutes during 10-minute infusion and 25-minute recovery |