Sleep and Breathing in the General Population - Chemical Stimuli

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ClinicalTrials.gov Identifier: NCT04720547

Recruitment Status : Completed

First Posted : January 22, 2021

Last Update Posted : January 22, 2021

Sponsor:

Collaborator:

National Institutes of Health (NIH)

Information provided by (Responsible Party):

M Safwan Badr, Wayne State University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Sleep-disordered Breathing	Drug: Zolpidem	Phase 4

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 Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	11 participants
Allocation:	Randomized
Intervention Model:	Crossover Assignment
Intervention Model Description:	After an initial assessment to determine eligibility, participant complete two in-lab night studies in a randomized manner including one night with the administration of zolpidem and another without zolpidem.
Masking:	Single (Outcomes Assessor)
Masking Description:	Personnel conducting assessment of outcomes and data analysis are blinded to treatment.
Primary Purpose:	Treatment
Official Title:	Sleep and Breathing in Health and Disease (Part 2A - Chemical Stimuli, Sleep and Breathing in the General Population)
Actual Study Start Date :	July 3, 2018
Actual Primary Completion Date :	February 29, 2020
Actual Study Completion Date :	February 29, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Zolpidem Zolpidem tartrate

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Zolpidem Participants will be administered zolpidem prior to completing an in-lab night study.	Drug: Zolpidem A nonbenzodiazepine hypnotic Other Name: Ambien
No Intervention: Control Participants complete an in-lab night study without the administration of a drug.

Outcome Measures

Primary Outcome Measures :

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
Central apnea indices [ Time Frame: one night ]
Central apnea indices is used to indicate the severity of central sleep apnea
Respiratory arousal index [ Time Frame: one night ]
A measure of the frequency of respiratory-related arousals during sleep

Secondary Outcome Measures :

Controller gain [ Time Frame: one night ]
Controller gain is a ventilatory response to changes in end-tidal PCO2
Plant gain [ Time Frame: one night ]
Plant gain is blood gas response to a change in ventilation. This measure represents the effectiveness of the "plant" in eliminating CO2.
Carotid body function [ Time Frame: one night ]
This measure represents the activity of the carotid bodies. It is measured by the decrease in ventilation in response to a single breath of 100% oxygen
Respiratory arousal threshold [ Time Frame: one night ]
The nadir pressure in the upper airway (supra-glottic pressure) prior to the occurrence of an arousal

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes

Criteria

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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04720547

Locations

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United States, Michigan
John D. Dingell VA Medical Center
Detroit, Michigan, United States, 48201

Sponsors and Collaborators

Wayne State University

National Institutes of Health (NIH)

Investigators

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Principal Investigator:	M Safwan Badr, MD, MBA	John D. Dingell VA Medical Center, Detroit, MI

More Information

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Responsible Party:	M Safwan Badr, Chair of Internal Medicine, Wayne State University
ClinicalTrials.gov Identifier:	NCT04720547
Other Study ID Numbers:	1203010749
First Posted:	January 22, 2021 Key Record Dates
Last Update Posted:	January 22, 2021
Last Verified:	January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

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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

Keywords provided by M Safwan Badr, Wayne State University:


Sleep-disordered Breathing central sleep apnea

Additional relevant MeSH terms:

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Respiratory Aspiration Sleep Apnea Syndromes Respiration Disorders Respiratory Tract Diseases Pathologic Processes Apnea Sleep Disorders, Intrinsic Dyssomnias Sleep Wake Disorders Nervous System Diseases	Zolpidem Sleep Aids, Pharmaceutical Hypnotics and Sedatives Central Nervous System Depressants Physiological Effects of Drugs GABA-A Receptor Agonists GABA Agonists GABA Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action

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