Clinical trial NCT04720547: Sleep and Breathing in the General Population - Chemical Stimuli
Official title: Sleep and Breathing in Health and Disease (Part 2A - Chemical Stimuli, Sleep and Breathing in the General Population)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Sleep-disordered Breathing
Keywords: Sleep-disordered Breathing
central sleep apnea
Lead sponsor: Wayne State University
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2021-01-22
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
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.
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: The Central Apnea-hypopnea Index
timeFrame: one night
measure: Respiratory Arousal Index
timeFrame: one night
Secondary outcomes:
measure: CO2 Reserve
timeFrame: one night
measure: Controller Gain
timeFrame: one night
measure: Stead-State Plant Gain (mmHg
timeFrame: one night
measure: Respiratory Arousal Threshold
timeFrame: one night
Other outcomes:
Locations:
city: Detroit
country: United States
facility: John D. Dingell VA Medical Center
state: Michigan
Study officials:
affiliation: John D. Dingell VA Medical Center, Detroit, MI
name: M Safwan Badr, MD, MBA
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ahmad B, Sankari A, Eshraghi M, Aldwaikat A, Yarandi H, Zeineddine S, Salloum A, Badr MS. Effect of Zolpidem on nocturnal arousals and susceptibility to central sleep apnea. Sleep Breath. 2023 Mar;27(1):173-180. doi: 10.1007/s11325-022-02593-3. Epub 2022 Mar 14.