Opioid; Intoxication, Perception Disturbance (Acute)Phase 1NCT04301895
Pupillary Unrest in Ambient Light, and Relationship to Opioid-Induced Respiratory Depression
A Phase 1 study testing Continuous conversational interaction and Remifentanil infusion in people with Opioid; Intoxication, Perception Disturbance (Acute) and Acute Pain, run by University of California, San Francisco at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Opioid; Intoxication, Perception Disturbance (Acute), Acute Pain, Overdose of Opiate
- What is being tested?
- Continuous conversational interaction and Remifentanil infusion
- Type of treatment
- Injection or infusion, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Apr 2019to 3 Sep 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 20 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy
- Able to provide informed consent
Who cannot join
- Active substance use disorder
- Prior opioid use disorder
- Opioid use within 30 days.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California San Francisco
San Francisco, California, 94143
About this study
Official title: Pupillary Unrest in Ambient Light, and Relationship to Opioid-Induced Respiratory Depression in Volunteers
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.
Read the 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.
- Conditions
- Opioid; Intoxication, Perception Disturbance (Acute), Acute Pain, Overdose of Opiate, Respiratory Depression, Safety Issues
- Being tested
- Continuous conversational interaction, Remifentanil infusion
- Medical subject headings
- Acute Pain, Opiate Overdose, Respiratory Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Continuous conversational interactionBehavioural
Also called Environmental stimulation
Maintaining continuous conversation, requiring that the subject answer questions and engage in discussion without interruption.
Remifentanil infusionDrug
10 minute remifentanil infusion
| Study group | Role | What they receive |
|---|---|---|
| Interactive | Other | Subject will be asked to continually interactive with the investigators, answering a series of standard questions during the remifentanil infusion and recovery periods. Receives: Behavioral: Continuous conversational interaction; Drug: Remifentanil infusion |
| Non-interactive | Other | All verbal interaction will be avoided and extraneous sounds will be eliminated from the environment during the remifentanil infusion and recovery periods. Receives: Drug: Remifentanil infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Impact of environmental stimulation on decline in oxygen saturation to ≤ 90%.
Conversational interaction and oxygen saturation measured by pulse oximeter.
Measured: 35 minutes
Impact of environmental stimulation on CO2 increase of 15% or more above baseline.
Conversational interaction and CO2 measured by transcutaneous sensor.
Measured: 35 minutes
Correlation between estimated opioid concentration and deviation in pupillary measurement.
Relationship of opioid concentration to pupillary unrest, measured by the pupillometer
Measured: 35 minutes
Secondary outcomes (1)
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.
Measured: 35 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2020
- Study start30 Apr 2019
- Primary completion3 Sep 2019
- Study completion3 Sep 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Opioid; Intoxication, Perception Disturbance (Acute)Studies 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 1
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Model description
- Each subject is his/her own control.
- Masking
- None (open label)
- Enrolment
- 20 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, M.D., Principal investigator, Professor of Anesthesia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04301895
- Sponsor's protocol ID
- 221163
- Status last verified
- Mar 2020
- First submitted
- 3 Mar 2020
- Last updated
- 10 Mar 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- 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 33651243
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pupillary Unrest in Ambient Light, and Relationship to Opioid-Induced Respiratory Depression in Volunteers
- ClinicalTrials.gov ID
- NCT04301895
- Acronym / sponsor ID
- 221163
- Conditions
- Opioid; Intoxication, Perception Disturbance (Acute), Acute Pain, Overdose of Opiate, Respiratory Depression, Safety Issues
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Study start
- 30 Apr 2019 (actual)
- Primary completion
- 3 Sep 2019 (actual)
- Study completion
- 3 Sep 2019 (actual)
- First posted
- 10 Mar 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Each subject is his/her own control.
| Arm | Type | Receives |
|---|---|---|
| Interactive | Other | Behavioral: Continuous conversational interaction, Drug: Remifentanil infusionSubject will be asked to continually interactive with the investigators, answering a series of standard questions during the remifentanil infusion and recovery periods. |
| Non-interactive | Other | Drug: Remifentanil infusionAll verbal interaction will be avoided and extraneous sounds will be eliminated from the environment during the remifentanil infusion and recovery periods. |
Who may qualify
- Ages
- 20 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Healthy
- Able to provide informed consent
Key exclusion criteria (3 listed)
- Active substance use disorder
- Prior opioid use disorder
- Opioid use within 30 days.
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 |
|---|---|---|
| Continuous conversational interactionAlso: Environmental stimulationMaintaining continuous conversation, requiring that the subject answer questions and engage in discussion without interruption. | Behavioural | Interactive |
| Remifentanil infusion10 minute remifentanil infusion | Drug | Interactive, Non-interactive |
Primary outcome
Impact of environmental stimulation on decline in oxygen saturation to ≤ 90%.
Time frame: 35 minutes
Conversational interaction and oxygen saturation measured by pulse oximeter.
Impact of environmental stimulation on CO2 increase of 15% or more above baseline.
Time frame: 35 minutes
Conversational interaction and CO2 measured by transcutaneous sensor.
Correlation between estimated opioid concentration and deviation in pupillary measurement.
Time frame: 35 minutes
Relationship of opioid concentration to pupillary unrest, measured by the pupillometer
1 secondary outcome
Impact of environmental stimulation on opioid-related deviations in pupillary measurements.
Time frame: 35 minutes
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2020.
- Derived from this study: 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.
- Individual participant dataSharing planned: No
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, M.D. 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 1 study testing Continuous conversational interaction and Remifentanil infusion in people with Opioid; Intoxication, Perception Disturbance (Acute) and Acute Pain, 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 2 inclusion and 3 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 10 Mar 2020. 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 phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Impact of environmental stimulation on decline in oxygen saturation to ≤ 90%. (time frame: 35 minutes). The study lists 3 primary outcomes in all. 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 NCT04301895, which also lists 1 linked publication.
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 10 Mar 2020.