Pupillary Unrest in Ambient Light, and Relationship to Opioid-Induced Respiratory Depression

Phase 1

Completed

• Conditions: Opioid; Intoxication, Perception Disturbance (Acute); Respiratory Depression; Safety Issues; Acute Pain; Overdose of Opiate
• Interventions: Behavioral: Continuous conversational interaction; Drug: Remifentanil infusion

• Registration Number: NCT04301895
• Lead Sponsor: University of California, San Francisco

Brief Summary

Volunteers will receive a weight-based opioid (remifentanil) infusion for 10 minutes. In the first run, serial pupillary measurements (pupillary unrest, pupil diameter) will be taken at baseline, and at 2.5-minute intervals during the infusion and a 25-minute recovery period afterwards. After a washout period, the experiment will be repeated in each subject (second run). The two runs differ only by presence versus absence of verbal interaction.

Detailed Description

Healthy volunteers aged 20-55 will receive a weight-based opioid (remifentanil) infusion for 10 minutes. Vital signs including SpO2, transcutaneous CO2, and respiratory rate will be continuously measured.

In the first run, serial pupillary measurements (pupillary unrest, pupil diameter) will be taken at baseline, and at 2.5-minute intervals during the infusion and a 25-minute recovery period afterwards. After a washout period, the experiment will be repeated in each subject (second run). The two runs differ only by presence of ongoing verbal interaction versus complete avoidance of verbal interaction.

Incidence of respiratory depression will be compared in the two protocols with or without verbal interaction. Correlation between pupil diameter and pupillary unrest with estimated opioid concentrations will be determined by regression. Difference between pupil measurement versus opioid concentration regressions will be compared by chi2.

Study Timeline

• Study Start: 2019-04-30
• Primary Completion: 2019-09-03
• Study Completion: 2019-09-03
• Status Verified: 2020-03
• Study First Submitted: 2020-03-03
• Study First Submitted QC: 2020-03-05
• Last Update Submitted: 2020-03-05
• Study First Posted: 2020-03-10
• Last Update Posted: 2020-03-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

• Healthy
• Able to provide informed consent

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Exclusion Criteria

• Active substance use disorder
• Prior opioid use disorder
• Opioid use within 30 days.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Interactive	Remifentanil infusion	Subject will be asked to continually interactive with the investigators, answering a series of standard questions during the remifentanil infusion and recovery periods.
Non-interactive	Remifentanil infusion	All verbal interaction will be avoided and extraneous sounds will be eliminated from the environment during the remifentanil infusion and recovery periods.
Interactive	Continuous conversational interaction	Subject will be asked to continually interactive with the investigators, answering a series of standard questions during the remifentanil infusion and recovery periods.

Primary Outcome Measures

Name	Time	Method
Impact of environmental stimulation on decline in oxygen saturation to ≤ 90%.	35 minutes	Conversational interaction and oxygen saturation measured by pulse oximeter.
Impact of environmental stimulation on CO2 increase of 15% or more above baseline.	35 minutes	Conversational interaction and CO2 measured by transcutaneous sensor.
Correlation between estimated opioid concentration and deviation in pupillary measurement.	35 minutes	Relationship of opioid concentration to pupillary unrest, measured by the pupillometer

Secondary Outcome Measures

Name	Time	Method
Impact of environmental stimulation on opioid-related deviations in pupillary measurements.	35 minutes	Impact of conversational interaction on degree of decline in pupillary unrest as measured by the pupillometer.

Trial Locations

Locations (1)

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