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

Respiratory Depression Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05391555
• Other study ID #: 21-34917
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: October 1, 2022
• Est. completion date: August 31, 2023

Study information

• Verified date: October 2022
• Source: University of California, San Francisco
• Contact: Rachel Eshima McKay, MD
• Phone: 415-502-1715
• Email: rachel.eshima[@]ucsf.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: August 31, 2023
• Est. primary completion date: August 31, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 40 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Miosis
• Opioid Toxicity
• Respiratory Depression
• Respiratory Insufficiency

Intervention

Drug:
• Remifentanil Hydrochloride
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.

Device:
• Pupillometry measurement
The pupil will be examined with the pupillometer at regular intervals, before during and after the opioid infusion

Locations

Country	Name	City	State
United States	University of California San Francisco	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, San Francisco

Country where clinical trial is conducted

United States, 

References & 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area Under the Time Concentration Curve (AUC 0-35 minutes)	PUAL measured by pupillometer.	Baseline, and every 2.5 minutes during 10-minute infusion and 25-minute recovery