Clinical trial

Central Sleep Apnea: Physiologic Mechanisms to Inform Treatment

Name
NURR-001-19S
Description
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.
Trial arms
Trial start
2021-01-07
Estimated PCD
2025-06-30
Trial end
2025-12-31
Status
Recruiting
Phase
Early phase I
Treatment
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.
Arms:
acetazolamide
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.
Arms:
zolpidem
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.
Arms:
buspirone
Size
200
Primary endpoint
CO2 reserve
120 days
Central apnea indices
120 days
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
Protocol
{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE4'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'CROSSOVER', 'interventionModelDescription': 'Specific Aim (1) is to determine the effect of combination therapy aiming to dampen chemoreceptor sensitivity AND decreasing plant gain. We hypothesize that combined therapy with PAP, acetazolamide and oxygen will be superior to each intervention alone in reducing CAHI and the CO2 reserve during sleep in patients with central sleep apnea. Specific Aim (2) is to determine the effect of decreasing respiratory-related arousals on the propensity to develop central apnea. We hypothesize that administration of PAP and zolpidem, will decrease respiratory-related arousals, CAHI and the CO2 reserve during sleep in patients with CSA compared to placebo. Specific Aim (3) is to determine the effect of augmenting serotonin A1 receptor activity on breathing during sleep. We hypothesize that administration of PAP and buspirone, a serotonin A1 receptor agonist; will reduce the propensity to central apnea during sleep in Veterans with central sleep apnea.', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'DOUBLE', 'whoMasked': ['PARTICIPANT', 'OUTCOMES_ASSESSOR']}}, 'enrollmentInfo': {'count': 200, 'type': 'ESTIMATED'}}
Updated at
2024-05-02

1 organization

3 products

2 indications

Indication
Able Bodied
Product
Zolpidem
Product
Buspirone