Opioid ToxicityPhase 2/3NCT05391555
Pupillary Unrest as an Indicator of Central Opioid Effect in Subjects 40-60 Years of Age
A Phase 2/3 study testing Remifentanil Hydrochloride and Pupillometry measurement in people with Opioid Toxicity and Pupillary Miosis, run by University of California, San Francisco at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 40 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Opioid Toxicity, Pupillary Miosis, Respiratory Depression
- What is being tested?
- Remifentanil Hydrochloride and Pupillometry measurement
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2022to 3 Jun 2023
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy, BMI < 35 kg/m2
Who cannot join
- 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,
Show all 11Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California San Francisco
San Francisco, California, 94143
About this study
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.
Read the 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.
- Conditions
- Opioid Toxicity, Pupillary Miosis, Respiratory Depression
- Being tested
- Remifentanil Hydrochloride, Pupillometry measurement
- Medical subject headings
- Miosis, Respiratory Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Remifentanil HydrochlorideDrug
Infusion of 0.2 µg/k/m for 5 minutes, the 0.3 µg/k/m for 5 minutes.
Pupillometry measurementDevice
Pupillary measurements were taken at baseline and every 2.5 minutes during the 10-minute infusion and 25-minute recovery period.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Remifentanil Hydrochloride; Device: Pupillometry measurement |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Baseline, and every 2.5 minutes during 10-minute infusion and 25-minute recovery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 May 2022
- Study start1 Oct 2022
- Primary completion3 Jun 2023
- Study completion3 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Opioid ToxicityStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Rachel Eshima McKay, MD, Principal investigator, Professor of Anesthesia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05391555
- Sponsor's protocol ID
- 21-34917
- Status last verified
- Apr 2025
- First submitted
- 13 May 2022
- Last updated
- 2 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 33651243McKay 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.
PubMed 34474355McKay 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.
PubMed 29608463
Study at a glance
From the registry record, last updated by the sponsor on 2 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pupillary Unrest as an Indicator of Central Opioid Effect in Subjects 40-60 Years of Age
- ClinicalTrials.gov ID
- NCT05391555
- Acronym / sponsor ID
- 21-34917
- Conditions
- Opioid Toxicity, Pupillary Miosis, Respiratory Depression
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Study start
- 1 Oct 2022 (actual)
- Primary completion
- 3 Jun 2023 (actual)
- Study completion
- 3 Jun 2023 (actual)
- First posted
- 26 May 2022 (actual)
- Results
- Posted 2 May 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Remifentanil Infusion and Recovery | Experimental | Drug: Remifentanil Hydrochloride, Device: Pupillometry measurementParticipants 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. |
Who may qualify
- Ages
- 40 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Healthy, BMI < 35 kg/m2
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Remifentanil HydrochlorideInfusion of 0.2 µg/k/m for 5 minutes, the 0.3 µg/k/m for 5 minutes. | Drug | Remifentanil Infusion and Recovery |
| Pupillometry measurementPupillary measurements were taken at baseline and every 2.5 minutes during the 10-minute infusion and 25-minute recovery period. | Device | Remifentanil Infusion and Recovery |
Primary outcome
Area Under the Time Concentration Curve (AUROC )
Time frame: Baseline, and every 2.5 minutes during 10-minute infusion and 25-minute recovery
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 33651243McKay 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.
- Background: PubMed 34474355McKay 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.
- Background: PubMed 29608463McKay 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.
- Individual participant dataSharing planned: No
Related trials for Opioid Toxicity
Not yet recruiting
Two Bupivacaine Concentrations for Recto-Intercostal Fascial Plane Block After Laparoscopic Cholecystectomy
Postoperative Pain, Acute Pain
Active, not recruitingPhase 1
STTEPP: Safety, Tolerability and Dose Limiting Toxicity of Lacosamide in Patients With Painful Chronic Pancreatitis
Chronic Pain, Chronic Pain Syndrome
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rachel Eshima McKay, MD principal investigator
Professor of Anesthesia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Remifentanil Hydrochloride and Pupillometry measurement in people with Opioid Toxicity and Pupillary Miosis, run by University of California, San Francisco at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area Under the Time Concentration Curve (AUROC ) (time frame: Baseline, and every 2.5 minutes during 10-minute infusion and 25-minute recovery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05391555, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 May 2025.