- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04720547
Sleep and Breathing in the General Population - Chemical Stimuli
December 4, 2023 updated by: M Safwan Badr, Wayne State University
Sleep and Breathing in Health and Disease (Part 2A - Chemical Stimuli, Sleep and Breathing in the General Population)
Central sleep apnea (CSA) is a common condition and its treatment remains elusive.
The focus of this proposal is to identify the role of the physiologic path involving cortical arousals in CSA by decreasing arousal frequency using the pharmacological agent zolpidem.
The goal is to identify the acute effects of administering zolpidem on sleep and respiratory outcomes, and subsequently, its effect on the severity of CSA and propensity to develop CSA.
This study will shed light on the mechanisms underlying CSA that involve cortical arousals and will guide future therapeutic interventions for CSA.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
The literature suggests that zolpidem may be effective in the treatment of central sleep apnea (CSA).
However, evidence regarding the efficacy of zolpidem and the underlying mechanisms involved in its effect on CSA are not well-studied.
Furthermore, respiratory-related arousals are hypothesized to contribute CSA symptoms and severity.
The aim of the study is to determine the effect of decreasing respiratory-related arousals on the propensity to develop central apnea.
The investigators hypothesize that administration of the nonbenzodiazepine hypnotic zolpidem will decrease the frequency of respiratory-related arousals, lower the central apnea-hypopnea index, and widen the CO2 reserve during sleep in patients with CSA compared to no treatment.
Participants will complete a night study on a low dose of zolpidem and another night study without zolpidem in a crossover manner.
The order of night studies is randomized.
The results will help unveil the role of arousals in CSA and the acute effect of zolpidem on CSA severity and the propensity to CSA.
Study Type
Interventional
Enrollment (Actual)
14
Phase
- Phase 4
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
-
-
Michigan
-
Detroit, Michigan, United States, 48201
- John D. Dingell VA Medical Center
-
-
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
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
Yes
Description
Inclusion Criteria:
- Men and women Veterans with central sleep apnea, defined as Apnea Hypopnea Index (AHI)>15/hour with CAHI>5/hour, will be included in the experiments.
Exclusion Criteria:
- less than 18 years old
- pregnant or breastfeeding female
- have severe respiratory disease that require to be on oxygen
- recent health event that may affect the ability to participate in the study,
- Body Mass Index (BMI) is >40 kg/m2
- significant insomnia
- mental instability
- recent health event that may affect sleep
- if at any time the principal investigator (PI) identifies that a certain drug is not suitable, or are unable to use the device that is used to treat sleep apnea, will be not be allowed to participate in the study
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: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Zolpidem, then No Treatment
Participants will be administered zolpidem for the first night study, and No Treatment during the second night study.
|
A nonbenzodiazepine hypnotic
Other Names:
The Control condition in which participants do not receive medication.
|
Experimental: No Treatment, then Zolpidem
Participants will be administered zolpidem for the second night study, and No Treatment during the first night study.
|
A nonbenzodiazepine hypnotic
Other Names:
The Control condition in which participants do not receive medication.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The Central Apnea-hypopnea Index
Time Frame: one night
|
The number of central apneas and hypopneas per hour of sleep was obtained from polysomnography studies.
|
one night
|
Respiratory Arousal Index
Time Frame: one night
|
A measure of the frequency of respiratory-related arousals during sleep
|
one night
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
CO2 Reserve
Time Frame: one night
|
CO2 reserve is the requisite change to induce central apnea is referred to as the CO2 reserve, which can be positive or negative.
CO2 reserve is defined as the difference between the eupneic end-tidal CO2 pressure and the end-tidal CO2 pressure induced by the ventilation protocol that is sufficient to trigger a central apnea as defined by the American Academy of Sleep Medicine.
|
one night
|
Controller Gain
Time Frame: one night
|
Controller gain is a ventilatory response to changes in end-tidal PCO2.
Controller gain was calculated by dividing the difference in minute ventilation between the post-mechanical ventilation induced by the ventilation protocol and steady-state respiration by the difference in the end-tidal CO2 pressure between the mechanical ventilation and steady-state respiration.
|
one night
|
Stead-State Plant Gain (mmHg
Time Frame: one night
|
Plant gain is a blood gas response to a change in ventilation.
This measure represents the effectiveness of the "plant" in eliminating CO2.
Steady-state plant gain was calculated from the ratio of end-tidal CO2 to minute ventilation during stable respiration.
|
one night
|
Respiratory Arousal Threshold
Time Frame: one night
|
The nadir pressure in the upper airway (supra-glottic pressure) prior to the occurrence of an arousal
|
one night
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: M Safwan Badr, MD, MBA, John D. Dingell VA Medical Center, Detroit, MI
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
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)
July 3, 2018
Primary Completion (Actual)
February 29, 2020
Study Completion (Actual)
February 29, 2020
Study Registration Dates
First Submitted
January 20, 2021
First Submitted That Met QC Criteria
January 21, 2021
First Posted (Actual)
January 22, 2021
Study Record Updates
Last Update Posted (Estimated)
December 6, 2023
Last Update Submitted That Met QC Criteria
December 4, 2023
Last Verified
December 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Nervous System Diseases
- Respiratory Tract Diseases
- Apnea
- Respiration Disorders
- Sleep Disorders, Intrinsic
- Dyssomnias
- Sleep Wake Disorders
- Sleep Apnea Syndromes
- Respiratory Aspiration
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Hypnotics and Sedatives
- GABA Agents
- Sleep Aids, Pharmaceutical
- GABA-A Receptor Agonists
- GABA Agonists
- Zolpidem
Other Study ID Numbers
- 1203010749
- 5R01HL130552-05 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
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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