Apnea, SleepEarly Phase 1AROSANCT02898792
Remifentanil in Adults With OSA
A Early Phase 1 study testing Targeted infusion of remifentanil in people with Apnea, Sleep, run by Washington University School of Medicine at 1 site in United States.
Trial summary
Obstructive Sleep Apnea (OSA) is the most common problem that affects sleep. People with this problem have their airway blocked or minimized, causing snoring or gasping while sleeping. It can also reduce the amount of oxygen that circulates in the blood of people affected by it. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Apnea, Sleep
- What is being tested?
- Targeted infusion of remifentanil
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 77 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Sep 2016to 2 May 2018
- Phase
- Early 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 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 18 to 70 year-old males or non-pregnant females
- Provide informed consent
Who cannot join
- History of liver disease
- pregnant or nursing females
- known history of addiction to drugs or alcohol
- craniofacial anomalies that preclude proper fit of pupillometry goggles
- eye abnormalities that preclude the measurement of pupil diameter
- use of home oxygen
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University St Louis School of Medicine
St Louis, Missouri, 63110
About this study
Official title: Opioid Sensitivity in Adults With Treated and Untreated Obstructive Sleep Apnea
Obstructive Sleep Apnea (OSA) is the most common problem that affects sleep. People with this problem have their airway blocked or minimized, causing snoring or gasping while sleeping. It can also reduce the amount of oxygen that circulates in the blood of people affected by it. Millions of Americans have OSA; 10% of adults have diagnosed OSA, an estimated 25% have undiagnosed OSA. There is concern in the medical community about how to manage pain in patients with OSA because of the risk of decreased or slower breathing associated with certain pain medications called opioids. Giving OSA patients opioids could cause them to have even lower oxygen amounts in their blood stream. It is conceivable that patients with OSA may require lower doses of opioids to cause decreased breathing as compared to patients without OSA, however this has not been proven. In this study, we are using a very short acting and easily reversible opioid pain medication called remifentanil in patients with OSA in order to find out if treated and untreated OSA patients respond to opioid differently than patients without OSA.
Read the detailed description
Open-label, parallel group study. Twenty adults each with untreated OSA, CPAP-treated OSA, and no OSA will undergo a stepped-dose target-controlled opioid (remifentanil) infusion, measurement of opioid effects (miosis, respiratory rate, end-expired CO2, thermal analgesia) and plasma drug concentrations. Remifentanil clinical effects, pharmacodynamics (concentration-effect relationships), and pharmacokinetics will be compared between the three groups, as will relationships between effects and nighttime hypoxemia (assessed by home PSG).
The ultimate long-term goal for this research is to improve the perioperative care and pain management of patients with obstructive sleep apnea (OSA). While patients with OSA are believed to be more sensitive to the analgesic and adverse effects of opioids, there are no studies that assess the effects of the OSA gold-standard treatment, namely CPAP, on this purported sensitivity. Furthermore, OSA is a heterogeneous disease and not all patients who carry an OSA diagnosis are likely to have the same opioid sensitivity. At present no easily administered test is able to determine the degree of opioid sensitivity of an individual patient.
The specific goal of this research is to validate or refute, the untested yet "conventional wisdom" that adults with untreated OSA have increased sensitivity to the clinical effects of opioids, especially ventilatory depression. We will test the presumptive hypotheses that a) untreated OSA increases ventilatory, miotic, and analgesic effects of opioids, b) the magnitude of increase is proportional to the degree of nighttime hypoxia, and c) CPAP treatment of OSA normalizes altered opioid responses.
These hypotheses will be tested by evaluating the pharmacodynamics (concentration-effect relationship) of the prototype opioid remifentanil in patients with and without OSA using objective opioid sensitivity markers to determine if patients with OSA have increased sensitivity to opioids and to determine if treatment with CPAP alters this purported sensitivity. Our study drug, remifentanil, is an ultra-short acting μ-selective opioid agonist, which is the same receptor at which longer acting opioids such as morphine act. Since the site of action of remifentanil is the same as other opioids, the results of this study will be able to be generalized to other opioids, improving our clinical understanding and practice in this patient population. Opioid effects will be determined by the decrease in pupil diameter, which is the most sensitive measure of opioid effects at the drug concentrations and subanesthetic doses to be used. The degree to which changes in pupil diameter correlate with changes in respiratory rate will be compared.
- Conditions
- Apnea, Sleep
- Being tested
- Targeted infusion of remifentanil
- Keywords
- sensitivity, opioid
- Medical subject headings
- Sleep Apnea Syndromes, Hypersensitivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Targeted infusion of remifentanilDrug
Also called Ultiva
Remifentanil dosing will be calculated using ideal body weight and infused to achieve brain concentrations of 0.5, 1, 2, 3, and 4 ng/ml; approximately 10 minutes at each concentration.
| Study group | Role | What they receive |
|---|---|---|
| targeted infusion of remifentanil untreated OSA | Experimental | Stepped-dose, targeted infusion of remifentanil with measurement of miosis, respiratory rate, end-expired CO2, and thermal analgesia and plasma drug concentrations. Remifentanil dose will be based on ideal body weight. Receives: Drug: Targeted infusion of remifentanil |
| targeted infusion of remifentanil CPAP treated OSA | Experimental | Stepped-dose, targeted infusion of remifentanil with measurement of miosis, respiratory rate, end-expired CO2, and thermal analgesia and plasma drug concentrations. Remifentanil dose will be based on ideal body weight. Receives: Drug: Targeted infusion of remifentanil |
| targeted infusion of remifentanil No OSA | Experimental | Stepped-dose, targeted infusion of remifentanil with measurement of miosis, respiratory rate, end-expired CO2, and thermal analgesia and plasma drug concentrations. Remifentanil dose will be based on ideal body weight. Receives: Drug: Targeted infusion of remifentanil |
What is being measured
The primary outcome is the main question the study is designed to answer.
The relationship between remifentanil concentration and miotic effect
Measured: Baseline, 10, 20, 30, 40, and 50 minutes for each concentration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Sep 2016 (estimated)
- Study start16 Sep 2016
- Primary completion2 May 2018
- Study completion2 May 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Apnea, SleepStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe 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
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 77 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Evan Kharasch, MD, PhD, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02898792
- Sponsor's protocol ID
- 201605158
- Acronym
- AROSA
- Status last verified
- Oct 2018
- First submitted
- 8 Sep 2016
- Last updated
- 4 Oct 2018
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Maharaj AR, Montana MC, Hornik CP, Kharasch ED. Opioid use in treated and untreated obstructive sleep apnoea: remifentanil pharmacokinetics and pharmacodynamics in adult volunteers. Br J Anaesth. 2025 Mar;134(3):681-692. doi: 10.1016/j.bja.2024.10.042. Epub 2025 Jan 20.
PubMed 39837697Montana MC, McLeland M, Fisher M, Juriga L, Ercole PM, Kharasch ED. Opioid sensitivity in treated and untreated obstructive sleep apnoea: a prospective cohort study. Br J Anaesth. 2024 Jan;132(1):145-153. doi: 10.1016/j.bja.2023.09.032. Epub 2023 Nov 7.
PubMed 37945413
Study at a glance
From the registry record, last updated by the sponsor on 4 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Opioid Sensitivity in Adults With Treated and Untreated Obstructive Sleep Apnea
- ClinicalTrials.gov ID
- NCT02898792
- Acronym / sponsor ID
- AROSA / 201605158
- Conditions
- Apnea, Sleep
- Keywords
- sensitivity, opioid
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 77 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Study start
- 16 Sep 2016 (actual)
- Primary completion
- 2 May 2018 (actual)
- Study completion
- 2 May 2018 (actual)
- First posted
- 13 Sep 2016 (estimated)
- 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.
Obstructive Sleep Apnea (OSA) is the most common problem that affects sleep. People with this problem have their airway blocked or minimized, causing snoring or gasping while sleeping. It can also reduce the amount of oxygen that circulates in the blood of people affected by it. Millions of Americans have OSA; 10% of adults have diagnosed OSA, an estimated 25% have undiagnosed OSA. There is concern in the medical community about how to manage pain in patients with OSA because of the risk of decreased or slower breathing associated with certain pain medications called opioids. Giving OSA patients opioids could cause them to have even lower oxygen amounts in their blood stream. It is conceivable that patients with OSA may require lower doses of opioids to cause decreased breathing as compared to patients without OSA, however this has not been proven. In this study, we are using a very short acting and easily reversible opioid pain medication called remifentanil in patients with OSA in order to find out if treated and untreated OSA patients respond to opioid differently than patients without OSA.
Detailed description
Open-label, parallel group study. Twenty adults each with untreated OSA, CPAP-treated OSA, and no OSA will undergo a stepped-dose target-controlled opioid (remifentanil) infusion, measurement of opioid effects (miosis, respiratory rate, end-expired CO2, thermal analgesia) and plasma drug concentrations. Remifentanil clinical effects, pharmacodynamics (concentration-effect relationships), and pharmacokinetics will be compared between the three groups, as will relationships between effects and nighttime hypoxemia (assessed by home PSG).
The ultimate long-term goal for this research is to improve the perioperative care and pain management of patients with obstructive sleep apnea (OSA). While patients with OSA are believed to be more sensitive to the analgesic and adverse effects of opioids, there are no studies that assess the effects of the OSA gold-standard treatment, namely CPAP, on this purported sensitivity. Furthermore, OSA is a heterogeneous disease and not all patients who carry an OSA diagnosis are likely to have the same opioid sensitivity. At present no easily administered test is able to determine the degree of opioid sensitivity of an individual patient.
The specific goal of this research is to validate or refute, the untested yet "conventional wisdom" that adults with untreated OSA have increased sensitivity to the clinical effects of opioids, especially ventilatory depression. We will test the presumptive hypotheses that a) untreated OSA increases ventilatory, miotic, and analgesic effects of opioids, b) the magnitude of increase is proportional to the degree of nighttime hypoxia, and c) CPAP treatment of OSA normalizes altered opioid responses.
These hypotheses will be tested by evaluating the pharmacodynamics (concentration-effect relationship) of the prototype opioid remifentanil in patients with and without OSA using objective opioid sensitivity markers to determine if patients with OSA have increased sensitivity to opioids and to determine if treatment with CPAP alters this purported sensitivity. Our study drug, remifentanil, is an ultra-short acting μ-selective opioid agonist, which is the same receptor at which longer acting opioids such as morphine act. Since the site of action of remifentanil is the same as other opioids, the results of this study will be able to be generalized to other opioids, improving our clinical understanding and practice in this patient population. Opioid effects will be determined by the decrease in pupil diameter, which is the most sensitive measure of opioid effects at the drug concentrations and subanesthetic doses to be used. The degree to which changes in pupil diameter correlate with changes in respiratory rate will be compared.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| targeted infusion of remifentanil untreated OSA | Experimental | Drug: Targeted infusion of remifentanilStepped-dose, targeted infusion of remifentanil with measurement of miosis, respiratory rate, end-expired CO2, and thermal analgesia and plasma drug concentrations. Remifentanil dose will be based on ideal body weight. |
| targeted infusion of remifentanil CPAP treated OSA | Experimental | Drug: Targeted infusion of remifentanilStepped-dose, targeted infusion of remifentanil with measurement of miosis, respiratory rate, end-expired CO2, and thermal analgesia and plasma drug concentrations. Remifentanil dose will be based on ideal body weight. |
| targeted infusion of remifentanil No OSA | Experimental | Drug: Targeted infusion of remifentanilStepped-dose, targeted infusion of remifentanil with measurement of miosis, respiratory rate, end-expired CO2, and thermal analgesia and plasma drug concentrations. Remifentanil dose will be based on ideal body weight. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 18 to 70 year-old males or non-pregnant females
- Provide informed consent
Key exclusion criteria (6 listed)
- History of liver disease
- pregnant or nursing females
- known history of addiction to drugs or alcohol
- craniofacial anomalies that preclude proper fit of pupillometry goggles
- eye abnormalities that preclude the measurement of pupil diameter
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 |
|---|---|---|
| Targeted infusion of remifentanilAlso: UltivaRemifentanil dosing will be calculated using ideal body weight and infused to achieve brain concentrations of 0.5, 1, 2, 3, and 4 ng/ml; approximately 10 minutes at each concentration. | Drug | targeted infusion of remifentanil CPAP treated OSA, targeted infusion of remifentanil No OSA, targeted infusion of remifentanil untreated OSA |
Primary outcome
The relationship between remifentanil concentration and miotic effect
Time frame: Baseline, 10, 20, 30, 40, and 50 minutes for each concentration
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 4 Oct 2018.
- Derived from this study: PubMed 39837697Maharaj AR, Montana MC, Hornik CP, Kharasch ED. Opioid use in treated and untreated obstructive sleep apnoea: remifentanil pharmacokinetics and pharmacodynamics in adult volunteers. Br J Anaesth. 2025 Mar;134(3):681-692. doi: 10.1016/j.bja.2024.10.042. Epub 2025 Jan 20.
- Derived from this study: PubMed 37945413Montana MC, McLeland M, Fisher M, Juriga L, Ercole PM, Kharasch ED. Opioid sensitivity in treated and untreated obstructive sleep apnoea: a prospective cohort study. Br J Anaesth. 2024 Jan;132(1):145-153. doi: 10.1016/j.bja.2023.09.032. Epub 2023 Nov 7.
- Individual participant dataSharing planned: No
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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.
Evan Kharasch, MD, PhD principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Targeted infusion of remifentanil in people with Apnea, Sleep, run by Washington University School of Medicine 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 6 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 4 Oct 2018. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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?
The relationship between remifentanil concentration and miotic effect (time frame: Baseline, 10, 20, 30, 40, and 50 minutes for each concentration). 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 NCT02898792, which also lists 2 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 4 Oct 2018.