Recruiting

Central Sleep Apnea

Sponsor:

VA Office of Research and Development

Code:

NCT04118387

Conditions

Sleep Disordered Breathing

Able Bodied

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Accepted

Interventions

Acetazolamide + supplemental oxygen + PAP therapy

Zolpidem + PAP therapy

Buspirone + PAP therapy

Study Details

Brief summary:

Central sleep apnea (CSA) is common in patients with heart failure and those using opioid analgesics. Unfortunately, effective treatment of central apnea remains elusive, pressure therapy given the modest efficiency of positive airway pressure therapy. The focus of this proposal is to identify mechanistic pathways to guide future therapeutic interventions for central sleep apnea based on the strong premise that multi-modality therapy will normalize respiration and hence mitigate adverse long-term consequences of CSA. The investigators' proposed studies will test combination therapies, including positive airway pressure (PAP) plus a pharmacological agent who have heart failure or are using opioid analgesics. The investigators anticipate that findings will inform future clinical trials to improve care and quality of life among Veterans suffering from central sleep apnea, which remains difficult to treat using existing approaches.

Conditions

Sleep Disordered Breathing

Able Bodied

Study ID

NCT04118387

Start date

Jan 7, 2021

Status verified date

Jul, 2026

Completion date

Jun 30, 2027

Anticipated

Primary completion date

Dec 31, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Accepted

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 Design

Enrollment

200 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

active comparator: acetazolamide

To determine the effect of dampening chemoreceptor sensitivity AND decreasing plant gain. The investigators hypothesize that combined therapy with PAP, acetazolamide and oxygen will be superior to PAP plus each intervention alone or placebo in reducing CAHI and the CO2 reserve during sleep in Veterans with CSA.

active comparator: zolpidem

To determine the effect of decreasing respiratory-related arousals on the propensity to develop central apnea. The investigators hypothesize that administration of PAP and zolpidem, will decrease respiratory-related arousals, CAHI and the CO2 reserve during sleep in Veterans with CSA compared to PAP plus placebo.

active comparator: buspirone

To determine the effect of augmenting serotonin A1 receptor activity on breathing during sleep. The investigators hypothesize that administration of PAP and buspirone, a serotonin A1 receptor agonist; will reduce the propensity to central apnea during sleep in Veterans with CSA compared to PAP plus placebo.

Interventions

Acetazolamide + supplemental oxygen + PAP therapy

Every participant will undergo measurement of the apneic threshold. The apneic threshold (AT) can be determined by inducing central apnea using non-invasive ventilation (NIV) or eliminating central apnea using supplemental CO2. The requisite change to induce central apnea is referred to as the CO2 reserve, which can be positive or negative. The central apnea index and the apneic threshold will be measured while participants receiving medication or oxygen (or both). In addition, participants will get PAP therapy during all the conditions.

Zolpidem + PAP therapy

The central apnea index and the apneic threshold will be compared under two conditions: zolpidem or placebo. In addition, participants will get PAP therapy during both the conditions.

Buspirone + PAP therapy

The central apnea index and the apneic threshold will be compared under two conditions: buspirone or placebo. In addition, participants will get PAP therapy during both the conditions.

Primary outcome measure

  • CO2 reserve [ Time Frame: 120 days ]
  • Central apnea indices [ Time Frame: 120 days ]

Central Contacts and Locations

Central contacts

M S Badr, MD

(313) 576-1000sbadr@med.wayne.edu

Locations

John D. Dingell VA Medical Center, Detroit, MI

Recruiting

Detroit, Michigan, United States, 48201-1916

Contacts

Edi Levi, MD

(313) 576-4451edi.levi@va.gov

Erin Olgren, PhD MS

(313) 576-4448erin.olgren@va.gov

Principal Investigator:

M Safwan Badr, MD

More Information

Sponsor

VA Office of Research and Development

Last update posted

Jul 20, 2026

Last verified

Jul, 2026

Keywords

  • Central sleep apnea
  • Polysomnography (PSG)
  • Respiratory arousal threshold
  • Apnea Hypopnea index
  • Central Apnea Hypopnea Index
  • Breathing instability
  • Apneic Threshold (AT)
  • Peripheral chemoreflex sensitivity
  • CO2 reserve
  • Plant gain
  • Controller gain

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by VA Office of Research and Development on 2026-07-20.