NCT05391555

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

Completed Phase 2, PHASE3 Results posted Last updated 2 May 2025

What this trial tests

Phase 2, PHASE3 trial testing Remifentanil Hydrochloride in Opioid Toxicity in 10 participants. Completed in 3 June 2023.

Timeline

1 October 2022

Primary endpoint
3 June 2023

3 June 2023

Quick facts

Lead sponsor	University of California, San Francisco
Phase	Phase 2, PHASE3
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	diagnostic
Enrollment	10
Start date	1 October 2022
Primary completion	3 June 2023
Estimated completion	3 June 2023
Sites	1 location across United States

Drugs / interventions tested

• Remifentanil Hydrochloride — full drug profile →
• Pupillometry measurement

Conditions studied

• Opioid Toxicity — all drugs for Opioid Toxicity →
• Pupillary Miosis — all drugs for Pupillary Miosis →
• Respiratory Depression — all drugs for Respiratory Depression →

Sponsor

University of California, San Francisco

Who can join

Adults 40 to 60, any sex, with Opioid Toxicity or Pupillary Miosis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Area Under the Time Concentration Curve (AUROC ) Primary · 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

Group	Value	95% CI
Remifentanil Infusion and Recovery	0.9700	0.9340 – 1.0000

Sponsor's own description

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.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. The effect of opioids on the light-off pupillary reflex.
   McKay RE, Larson MD. · · 2026 · PMID 41540509 · DOI 10.1186/s44158-026-00340-8
2. Impact of age on PUAL as an indicator of opioid effect in adult subjects.
   McKay RE, Kohn MA, Larson MD. · · 2026 · PMID 40824571 · DOI 10.1007/s10877-025-01340-9