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

NCT05391555 | Completed Phase 2 Results FDA Drug FDA Device

• 1 other identifier: 21-34917
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Opioid Toxicity; Pupillary Miosis; Respiratory Depression

Outcome Measures

Primary Outcomes (1)

• Area Under the Time Concentration Curve (AUROC )

  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

  Baseline, and every 2.5 minutes during 10-minute infusion and 25-minute recovery

Study Arms (1)

Remifentanil Infusion and Recovery

EXPERIMENTAL

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.

Drug: Remifentanil Hydrochloride; Device: Pupillometry measurement

Interventions

Remifentanil Hydrochloride DRUG

Infusion of 0.2 µg/k/m for 5 minutes, the 0.3 µg/k/m for 5 minutes.

Remifentanil Infusion and Recovery

Pupillometry measurement DEVICE

Pupillary measurements were taken at baseline and every 2.5 minutes during the 10-minute infusion and 25-minute recovery period.

Remifentanil Infusion and Recovery

Eligibility Criteria

• Age: 40 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy, BMI \< 35 kg/m2

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of California, San Francisco: lead

Study Sites (1)

University of California San Francisco

San Francisco, California, 94143, United States

Location

Related Publications (3)

• McKay RE, Kohn MA, Larson MD. Pupillary unrest, opioid intensity, and the impact of environmental stimulation on respiratory depression. J Clin Monit Comput. 2022 Apr;36(2):473-482. doi: 10.1007/s10877-021-00675-3. Epub 2021 Mar 2.

  PMID: 33651243 BACKGROUND

• McKay RE, Larson MD. Detection of opioid effect with pupillometry. Auton Neurosci. 2021 Nov;235:102869. doi: 10.1016/j.autneu.2021.102869. Epub 2021 Aug 18.

  PMID: 34474355 BACKGROUND

• McKay RE, Neice AE, Larson MD. Pupillary Unrest in Ambient Light and Prediction of Opioid Responsiveness: Case Report on Its Utility in the Management of 2 Patients With Challenging Acute Pain Conditions. A A Pract. 2018 May 15;10(10):279-282. doi: 10.1213/XAA.0000000000000710.

  PMID: 29608463 BACKGROUND

MeSH Terms

Conditions

Miosis; Respiratory Insufficiency

Interventions

Remifentanil

Condition Hierarchy (Ancestors)

Pupil Disorders; Neurologic Manifestations; Nervous System Diseases; Eye Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Respiration Disorders; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Propionates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Rachel Eshima McKay
• Organization: University of California San Francisco

rachel.eshima@ucsf.edu

415-476-9035

Study Officials

• Rachel Eshima McKay, MD

  Professor of Anesthesia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2022
• First Posted: May 26, 2022
• Study Start: October 1, 2022
• Primary Completion: June 3, 2023
• Study Completion: June 3, 2023
• Last Updated: May 2, 2025
• Results First Posted: May 2, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)