Remifentanil in Adults With OSA (AROSA)

October 2, 2018 updated by: Washington University School of Medicine

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
77

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University St Louis School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria

  1. 18 to 70 year-old males or non-pregnant females
  2. Provide informed consent

Exclusion Criteria

  1. History of liver disease
  2. pregnant or nursing females
  3. known history of addiction to drugs or alcohol
  4. craniofacial anomalies that preclude proper fit of pupillometry goggles
  5. eye abnormalities that preclude the measurement of pupil diameter
  6. use of home oxygen

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: targeted infusion of remifentanil untreated OSA
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.
Drug: Targeted infusion of remifentanil
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.
Other Names:
  • Ultiva
Experimental: targeted infusion of remifentanil CPAP treated OSA
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.
Drug: Targeted infusion of remifentanil
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.
Other Names:
  • Ultiva
Experimental: targeted infusion of remifentanil No OSA
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.
Drug: Targeted infusion of remifentanil
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.
Other Names:
  • Ultiva

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
The relationship between remifentanil concentration and miotic effect
Time Frame: Baseline, 10, 20, 30, 40, and 50 minutes for each concentration
Baseline, 10, 20, 30, 40, and 50 minutes for each concentration

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Washington University School of Medicine

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Evan Kharasch, MD, PhD, Washington University School of Medicine

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 16, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 2, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 2, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 8, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 12, 2016

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 13, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 4, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 2, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 201605158

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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