A Phase 4 interventional study of Acetazolamide + supplemental oxygen + PAP therapy and Zolpidem + PAP therapy in Sleep Disordered Breathing and Able Bodied, sponsored by VA Office of Research and Development. Recruiting at 1 site in United States. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-07-20.
Sponsored by VA Office of Research and Development · Phase 4, Interventional, and Treatment
Among 36 studies in Sleep Apnea, Central with a site in United States — 4 open to participants now, 6 under way, none of them phase 3. Sleep Apnea, Central · United States.
Among the 36 studies in Sleep Apnea, Central with a site in United States, this one is the 3rd largest by planned enrollment of the 29 interventional ones that give a count, is one of 5 that started in 2021, is one of 4 in phase 4, and was the 27th registered.
96 studies on the registry are indexed under Sleep Apnea, Central; 18 are open to participants now.
This study's planned enrollment of 200 is above the median of 40 across 54 interventional studies indexed under Sleep Apnea, Central.
Browse Sleep Apnea, Central studies →4 of the 36 studies in Sleep Apnea, Central with a site in United States are open now.
A study can be open while its sites in United States have not opened yet or have stopped. Only those recruiting at a site in United States →
Of the 13 Sleep Apnea, Central studies recruiting now, 8 (62%) set no upper age limit and 3 (23%) stop at 75 or younger; 4 take children under 18; 5 take healthy volunteers.
This study: 18 Years and older · all sexes · healthy volunteers too.
The full table on the hub →36 studies; the count open now beside each. This study's row is marked.
First in 2007; this study’s year is marked. 5 started in 2021.
Median enrollment 44 across the 29 interventional studies, 92 across the 7 observational. Of the 28 that completed or were terminated, 18 (64%) have results posted.
18 of 36 have an industry lead sponsor. The 10 most frequent:
VA Office of Research and Development is the lead sponsor of 1,771 studies on the registry; 392 are open to participants now.
Of its 213 completed or terminated interventional studies of FDA-regulated products, 185 (87%) have results posted.
VA Office of Research and Development has 5 studies filed under Sleep Apnea, Central — fewer than ten, so there is no comparison to draw.
2 of the studies in Sleep Apnea, Central with a site in United States that are under way reach primary completion within a year, 0 of them phase 3. Phase 3 first, then by date:
| Study | Primary completion |
|---|---|
| NCT06776432ShionogiSafety and Efficacy Study of Sivopixant, Acetazolamide and SASS-001 in Sleep Apnea | 2026-12-31 |
| NCT04118387VA Office of Research and DevelopmentCentral Sleep Apnea : Physiologic Mechanisms to Inform Treatment | 2026-12-31 |
Among the 36 studies in Sleep Apnea, Central with a site in United States, from their registry updates:
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.
All research activities are on hold due to COVID-19. The investigators updated enrollment start date and the investigators will update primary completion date and study completion date later.
This project is focused on identifying mechanistic pathways to guide future therapeutic interventions for central sleep apnea (CSA) based on the strong premise that multi-modality therapy - aiming to normalize respiration- is the requisite path to mitigating the long-term adverse consequences of CSA. The central hypothesis is that CSA reflects a combination of physiologic perturbations and may require combined modality therapy targeting different parts of the ventilatory feedback loop. The proposed studies will test combination therapies, including PAP plus a pharmacological agent. This will also increase the clinical relevance of the proposed studies since PAP therapy is typically prescribed as the initial treatment of CSA. To achieve the objectives of this proposal, the investigators will test the following three specific aims. Specific Aim (1) is to determine the effect of combination therapy aiming to dampen chemoreceptor sensitivity AND decreasing plant gain. The investigators hypothesize that combined therapy with PAP, acetazolamide and oxygen will be superior to each intervention alone in reducing central apnea-hypopnea index (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. The investigators 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. 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 central sleep apnea. This Novel project seeks to identify physiologic pathways that can, in combination with PAP therapy, improve the effectiveness of treatment for patients with CSA. The proposed studies are innovative, feasible and will provide a much-needed roadmap for future clinical trials that are likely to transform the care of central apnea in Veterans.
96 studies on the registry are indexed under Sleep Apnea, Central; 18 are open to participants now.
This study's planned enrollment of 200 is above the median of 40 across 54 interventional studies indexed under Sleep Apnea, Central.
Browse Sleep Apnea, Central studies →VA Office of Research and Development is the lead sponsor of 1,771 studies on the registry; 392 are open to participants now.
Of its 213 completed or terminated interventional studies of FDA-regulated products, 185 (87%) have results posted.
Compared within Sleep Apnea, Central, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Sleep Apnea Syndromes. The counts are of registry records indexed under each term, refreshed daily. How we classify →
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Drug: Acetazolamide + supplemental oxygen + PAP therapy
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.
Drug: Zolpidem + PAP therapy
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.
Drug: Buspirone + 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.
Drug page: Zolpidem
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.
Drug page: Buspirone
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.
CO2 reserve
CO2 reserve is the requisite change to induce central apnea is referred to as the CO2 reserve, which can be positive or negative.
Time frame: 120 days
Central apnea indices
Central apnea indices is used to indicate the severity of central sleep apnea
Time frame: 120 days
Controller gain
Controller gain is a ventilatory response to changes in end-tidal PCO2
Time frame: 120 days
Plant gain
Plant gain is blood gas response to a change in ventilation. This measure represents the effectiveness of the "plant" in eliminating CO2.
Time frame: 120 days
Carotid body function
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.
Time frame: 120 days
Peripheral chemoreflex sensitivity
Peripheral chemoreflex sensitivity is measured either via brief hypoxia or a single breath of CO2.
Time frame: 120 days
Respiratory arousal threshold
The nadir pressure in the upper airway (supra-glottic pressure) prior to the occurrence of an arousal.
Time frame: 120 days
% stable breathing
To assess breathing stability, the investigators will measure % stable breathing using minute ventilation (VE) and tidal volume (VT) coefficient of variation as indices of breathing instability.
Time frame: 120 days
Plan to share: No
No publications or documents are linked to this record.
Started Jan 2021 (actual). Primary completion is estimated for Dec 2026, 71 months after the start.
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Studies of the drugs tested here: Zolpidem · Buspirone
VA Office of Research and Development →