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

Primary Purpose

Opioid Toxicity, Pupillary Miosis, Respiratory Depression

Status

Recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Remifentanil Hydrochloride

Pupillometry measurement

About this trial

This is an interventional diagnostic trial for Opioid Toxicity

Eligibility Criteria

40 Years - 60 Years (Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

University of California San FranciscoRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Noninteractive, then Interactive

Interactive, then Noninteractive

Arm Description

Participants undergo the infusion under noninteractive conditions, followed by a second drug infusion under interactive conditions.

Participants undergo the infusion under interactive conditions, followed by a second drug infusion under noninteractive conditions.

Outcomes

Primary Outcome Measures

Area Under the Time Concentration Curve (AUC 0-35 minutes)

PUAL measured by pupillometer.

Secondary Outcome Measures

Full Information

NCT ID

NCT05391555

First Posted

May 13, 2022

Last Updated

October 4, 2022

Sponsor

University of California, San Francisco

1. Study Identification

Unique Protocol Identification Number

NCT05391555

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2022

Overall Recruitment Status

Recruiting

Study Start Date

October 1, 2022 (Actual)

Primary Completion Date

August 31, 2023 (Anticipated)

Study Completion Date

August 31, 2023 (Anticipated)

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

Yes

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

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

Opioid Toxicity, Pupillary Miosis, Respiratory Depression

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Phase 2, Phase 3

Interventional Study Model

Crossover Assignment

Masking

None (Open Label)

Masking Description

The investigator determining the PUAL will be blinded to the opioid level concurrent with the measurement.

Allocation

Randomized

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Noninteractive, then Interactive

Arm Type

Experimental

Arm Description

Participants undergo the infusion under noninteractive conditions, followed by a second drug infusion under interactive conditions.

Arm Title

Interactive, then Noninteractive

Arm Type

Experimental

Arm Description

Participants undergo the infusion under interactive conditions, followed by a second drug infusion under noninteractive conditions.

Intervention Type

Drug

Intervention Name(s)

Remifentanil Hydrochloride

Intervention Description

Infusion of 0.2 µg/k/m for 5 minutes, the 0.3 µg/k/m for 5 minutes. Pupillary measurements will be taken at baseline and every 2.5 minutes during the 10-minute infusion and 25-minute recovery period.

Intervention Type

Device

Intervention Name(s)

Pupillometry measurement

Intervention Description

The pupil will be examined with the pupillometer at regular intervals, before during and after the opioid infusion

Primary Outcome Measure Information:

Title

Area Under the Time Concentration Curve (AUC 0-35 minutes)

Description

PUAL measured by pupillometer.

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

40 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Rachel Eshima McKay, MD

Phone

415-502-1715

rachel.eshima@ucsf.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Rachel Eshima McKay, MD

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

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Rachel Eshima McKay, M.D.

Phone

415-502-1715

rachel.eshima@ucsf.edu

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

background

PubMed Identifier

34474355

Citation

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.

Results Reference

background

PubMed Identifier

29608463

Citation

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.

Results Reference

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

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