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

Phase 2

Completed

• Conditions: Opioid Toxicity; Pupillary Miosis; Respiratory Depression
• Interventions: Drug: Remifentanil Hydrochloride; Device: Pupillometry measurement

• Registration Number: NCT05391555
• Lead Sponsor: University of California, San Francisco

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2022-05-13
• Study First Submitted QC: 2022-05-20
• Study First Posted: 2022-05-26
• Study Start: 2022-10-01
• Primary Completion: 2023-06-03
• Study Completion: 2023-06-03
• Results First Submitted: 2024-09-06
• Status Verified: 2025-04
• Results First Submitted QC: 2025-04-30
• Last Update Submitted: 2025-04-30
• Results First Posted: 2025-05-02
• Last Update Posted: 2025-05-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 10

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Remifentanil Infusion and Recovery	Remifentanil Hydrochloride	Participants underwent a 10-minute remifentanil infusion. Pupillary measures were taken a baseline and every 2.5 minutes during the 10-minute infusion and 25-minute recovery period.
Remifentanil Infusion and Recovery	Pupillometry measurement	Participants underwent a 10-minute remifentanil infusion. Pupillary measures were taken a baseline and every 2.5 minutes during the 10-minute infusion and 25-minute recovery period.

Primary Outcome Measures

Name	Time	Method
Area Under the Time Concentration Curve (AUROC )	Baseline, and every 2.5 minutes during 10-minute infusion and 25-minute recovery	PUAL measured by pupillometer. PUAL at zero-moderate opioid concentration (\<1.8 ng/mL) versus high-toxic opioid concentration (\>2.5 ng/mL) were dichotomous classifiers.; Receiver Operating Characteristic curve constructed, with AUROC reported

Trial Locations

Locations (1)

University of California San Francisco; 🇺🇸 San Francisco, California, United States