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

Primary Purpose

Opioid; Intoxication, Perception Disturbance (Acute), Acute Pain, Overdose of Opiate

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Continuous conversational interaction

Remifentanil infusion

About this trial

This is an interventional diagnostic trial for Opioid; Intoxication, Perception Disturbance (Acute)

Eligibility Criteria

20 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Healthy
Able to provide informed consent

Exclusion Criteria:

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

Sites / Locations

University of California San Francisco

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Arm Label

Interactive

Non-interactive

Arm Description

Subject will be asked to continually interactive with the investigators, answering a series of standard questions during the remifentanil infusion and recovery periods.

All verbal interaction will be avoided and extraneous sounds will be eliminated from the environment during the remifentanil infusion and recovery periods.

Outcomes

Primary Outcome Measures

Impact of environmental stimulation on decline in oxygen saturation to ≤ 90%.

Conversational interaction and oxygen saturation measured by pulse oximeter.

Impact of environmental stimulation on CO2 increase of 15% or more above baseline.

Conversational interaction and CO2 measured by transcutaneous sensor.

Correlation between estimated opioid concentration and deviation in pupillary measurement.

Relationship of opioid concentration to pupillary unrest, measured by the pupillometer

Secondary Outcome Measures

Impact of environmental stimulation on opioid-related deviations in pupillary measurements.

Impact of conversational interaction on degree of decline in pupillary unrest as measured by the pupillometer.

Full Information

NCT ID

NCT04301895

First Posted

March 3, 2020

Last Updated

March 5, 2020

Sponsor

University of California, San Francisco

1. Study Identification

Unique Protocol Identification Number

NCT04301895

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2020

Overall Recruitment Status

Completed

Study Start Date

April 30, 2019 (Actual)

Primary Completion Date

September 3, 2019 (Actual)

Study Completion Date

September 3, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of California, San Francisco

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Opioid; Intoxication, Perception Disturbance (Acute), Acute Pain, Overdose of Opiate, Respiratory Depression, Safety Issues

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Phase 1

Interventional Study Model

Crossover Assignment

Model Description

Each subject is his/her own control.

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

20 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Interactive

Arm Type

Other

Arm Description

Subject will be asked to continually interactive with the investigators, answering a series of standard questions during the remifentanil infusion and recovery periods.

Arm Title

Non-interactive

Arm Type

Other

Arm Description

All verbal interaction will be avoided and extraneous sounds will be eliminated from the environment during the remifentanil infusion and recovery periods.

Intervention Type

Behavioral

Intervention Name(s)

Continuous conversational interaction

Other Intervention Name(s)

Environmental stimulation

Intervention Description

Maintaining continuous conversation, requiring that the subject answer questions and engage in discussion without interruption.

Intervention Type

Drug

Intervention Name(s)

Remifentanil infusion

Intervention Description

10 minute remifentanil infusion

Primary Outcome Measure Information:

Title

Impact of environmental stimulation on decline in oxygen saturation to ≤ 90%.

Description

Conversational interaction and oxygen saturation measured by pulse oximeter.

Time Frame

35 minutes

Title

Impact of environmental stimulation on CO2 increase of 15% or more above baseline.

Description

Conversational interaction and CO2 measured by transcutaneous sensor.

Time Frame

35 minutes

Title

Correlation between estimated opioid concentration and deviation in pupillary measurement.

Description

Relationship of opioid concentration to pupillary unrest, measured by the pupillometer

Time Frame

35 minutes

Secondary Outcome Measure Information:

Title

Impact of environmental stimulation on opioid-related deviations in pupillary measurements.

Description

Impact of conversational interaction on degree of decline in pupillary unrest as measured by the pupillometer.

Time Frame

35 minutes

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Healthy Able to provide informed consent Exclusion Criteria: Active substance use disorder Prior opioid use disorder Opioid use within 30 days.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Rachel Eshima McKay, M.D.

Organizational Affiliation

Professor of Anesthesia

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of California San Francisco

City

San Francisco

State/Province

California

ZIP/Postal Code

94143

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

33651243

Citation

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.

Results Reference

derived

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

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