Sleep Disordered BreathingPhase 4CSA-HFNCT07210606
Central Apnea in Heart Failure: Physiological Mechanisms to Inform Treatment
A Phase 4 study testing Trazodone + positive airway pressure (PAP) therapy and Oxygen + positive airway pressure (PAP) therapy in people with Sleep Disordered Breathing and Able Bodied, run by VA Office of Research and Development at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Sleep Disordered Breathing, Able Bodied
- What is being tested?
- Trazodone + positive airway pressure (PAP) therapy and Oxygen + positive airway pressure (PAP) therapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Sep 2026to 31 Dec 2030
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Men and women Veterans with central sleep apnea, defined as Apnea Hypopnea Index (AHI)>15/hour with CAHI>5/hour, will be included with the experiments
- Those with chronic, stable heart failure with reduced ejection fraction, receiving stable optimized guideline-based therapy and no hospitalizations or change in the medical regimen for the past 90 days before enrollment
Who cannot join
- Pregnant or breastfeeding females
- Moderate or severe obstructive or restrictive lung disease, including supplemental oxygen (O2) use
- Current treatment for central sleep apnea (CSA), including any form of positive airway pressure (PAP) in the past three months, or phrenic nerve situation
- Too ill to engage in the study procedures, inability to provide consent for participation
- A history of cardiac arrhythmia
- Alcohol or substance abuse (less than 90 days sobriety) or current participation in a treatment program
Show all 13Show fewer
- Depression or a history of suicidality
- Severe insomnia (ISI>21) or reported short sleep duration (<6 hours)
- Positive airway pressure (PAP)-emergent central sleep apnea
- Lack of positive airway pressure (PAP) acceptance/adherence after a one-week home PAP trial after enrollment
- Additional Trazodone Exclusions:
- Prolonged QT on baseline electrocardiogram (ECG), using medications that inhibit CYP3A4
- Patients with severe renal impairment (glomerular filtration rate (GFR) < 20 milliliters per minute/1.73 square meters) or end-stage renal disease
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
John D. Dingell VA Medical Center, Detroit, MI
Detroit, Michigan, 48201-1916
M S Badr, MD, (313) 576-1000 ext. 65710, sbadr@med.wayne.edu
Lynn M Huber, (313) 576-3106, lynn.huber@va.gov
About this study
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.
Read the detailed description
The objective in this project is to test mechanistic pathways to inform future clinical studies investigating the potential treatment of central sleep apnea (CSA) in Veterans with heart failure and reduced ejection fraction (HF). The long-term goal is to transform the care of Veterans living with these two conditions. The investigators will test two key determinants of recurrent CSA in Veterans with HF: augmented peripheral chemoreceptor activity and respiratory arousals. Specifically, the project will utilize a novel PAP plus approach, combining PAP therapy to alleviate upper airway obstruction with a specific intervention to target the mechanistic underpinnings of CSA. The experiments will capitalize on the plasticity of the carbon dioxide (CO2) reserve as the gateway to the resolution of CSA. The investigators will suppress arousals or dampen augmented PCR activity while maintaining upper airway patency with PAP. The long-term goal is to inform future multi-modality intervention studies. To this end, the following Specific Aims will be addressed in Veterans with HF and CSA. Specific Aim (1): To determine the effect of decreasing respiratory arousals on the propensity to CSA. The investigators hypothesize that combined PAP and trazodone therapy will be superior to PAP alone in elevating the arousal threshold, widening the CO2 reserve (primary outcome), and decreasing CSA indices. Specific Aim (2): To determine the effect of decreased peripheral chemoreceptor sensitivity on the propensity to CSA. The investigators hypothesize that combined PAP and supplemental O2 (targeting peripheral chemoreceptor sensitivity) will be superior to PAP alone in widening the CO2 reserve (primary outcome), reducing controller gain, and decreasing CSA indices. The proposed studies are innovative, testing mechanistic "PAP Plus" approach targeting underlying causes of CSA and alleviating upper airway obstruction with PAP. These studies will inform future clinical trials to transform central apnea care in patients with heart failure.
- Conditions
- Sleep Disordered Breathing, Able Bodied
- Being tested
- Trazodone + positive airway pressure (PAP) therapy, Oxygen + positive airway pressure (PAP) therapy
- 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, Cheyne Stokes Breathing (CSB), Carotid Body Function, Peripheral Chemoresponsiveness, Heart Failure
- Medical subject headings
- Sleep Apnea Syndromes, Sleep Apnea, Central, Cheyne-Stokes Respiration, Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Trazodone + positive airway pressure (PAP) therapyDrug
The central apnea index and the apneic threshold will be compared under two conditions: trazodone or placebo. In addition, participants will get PAP therapy during both the conditions.
Oxygen + positive airway pressure (PAP) therapyDrug
The central apnea index and the apneic threshold will be compared under two conditions: oxygen or room air. In addition, participants will get PAP therapy during both the conditions.
| Study group | Role | What they receive |
|---|---|---|
| Trazodone | Active comparator | To determine the effect of dampening respiratory arousals. The investigators hypothesize that positive airway pressure (PAP) therapy with trazodone at 100 milligrams will be superior to CPAP alone in widening the carbon dioxide (CO2) reserve during sleep, decreasing respiratory arousals, and increasing the arousal threshold. Receives: Drug: Trazodone + positive airway pressure (PAP) therapy |
| Oxygen | Active comparator | To determine the effect of dampening peripheral chemoreceptor sensitivity. The investigators hypothesize that supplemental oxygen will be superior to CPAP alone in widening the carbon dioxide (CO2) reserve during sleep. The secondary analysis will use CAI as supplemental oxygen, which may obscure the detection of hypopneas based on desaturation. Receives: Drug: Oxygen + positive airway pressure (PAP) therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Carbon dioxide (CO2) Reserve
CO2 reserve is the requisite change to induce central apnea to as the CO2 reserve, which can be positive or negative.
Measured: 120 days
Secondary outcomes (5)
Peripheral Chemoresponsiveness
Peripheral chemoreflex sensitivity/Peripheral chemoresponsiveness is measured either via brief hypoxia or a single breath of carbon dioxide (CO2).
Measured: 120 days
Arousal Threshold
Arousal threshold is a measure of the upper airway muscle response to an obstructive sleep event.
Measured: 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.
Measured: 120 days
Controller gain
Controller gain is a ventilatory response to changes in end-tidal PCO2.
Measured: 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 carbon dioxide (CO2).
Measured: 120 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Oct 2025
- Study start16 Sep 2026
- Primary completion30 Jun 2030 (estimated)
- Study completion31 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sleep Disordered BreathingStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Specific Aim (1) is to determine the effect of decreasing respiratory arousals on the propensity to central sleep apnea (CSA). The investigators hypothesize that combined therapy with PAP and trazodone will be superior to PAP alone in elevating the arousal threshold, widening the CO2 reserve, and decreasing CSA indices. Specific Aim (2) is to determine the effect of decreased peripheral chemoreceptor sensitivity on the propensity to CSA. The investigators hypothesize that combined therapy with PAP and supplemental oxygen (O2) will be superior to positive airway pressure (PAP) alone in widening the carbon dioxide (CO2) reserve, reducing controller gain, and decreasing CSA indices.
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- M Safwan Badr, MD, Principal investigator, John D. Dingell VA Medical Center, Detroit, MI
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07210606
- Sponsor's protocol ID
- NURR-010-25S
- Other IDs
- 2I01RD001576-07A1
- Acronym
- CSA-HF
- Status last verified
- Oct 2026
- First submitted
- 29 Sep 2025
- Last updated
- 13 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Central Apnea in Heart Failure: Physiological Mechanisms to Inform Treatment
- ClinicalTrials.gov ID
- NCT07210606
- Acronym / sponsor ID
- CSA-HF / NURR-010-25S
- Conditions
- Sleep Disordered Breathing, Able Bodied
- Keywords
- Central Sleep Apnea, Polysomnography (PSG), Respiratory Arousal Threshold, Apnea Hypopnea Index, Central Apnea Hypopnea Index, Breathing Instability, Apneic Threshold (AT), Peripheral Chemoreflex Sensitivity
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- 16 Sep 2026 (actual)
- Primary completion
- 30 Jun 2030 (estimated)
- Study completion
- 31 Dec 2030 (estimated)
- First posted
- 7 Oct 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The objective in this project is to test mechanistic pathways to inform future clinical studies investigating the potential treatment of central sleep apnea (CSA) in Veterans with heart failure and reduced ejection fraction (HF). The long-term goal is to transform the care of Veterans living with these two conditions. The investigators will test two key determinants of recurrent CSA in Veterans with HF: augmented peripheral chemoreceptor activity and respiratory arousals. Specifically, the project will utilize a novel PAP plus approach, combining PAP therapy to alleviate upper airway obstruction with a specific intervention to target the mechanistic underpinnings of CSA. The experiments will capitalize on the plasticity of the carbon dioxide (CO2) reserve as the gateway to the resolution of CSA. The investigators will suppress arousals or dampen augmented PCR activity while maintaining upper airway patency with PAP. The long-term goal is to inform future multi-modality intervention studies. To this end, the following Specific Aims will be addressed in Veterans with HF and CSA. Specific Aim (1): To determine the effect of decreasing respiratory arousals on the propensity to CSA. The investigators hypothesize that combined PAP and trazodone therapy will be superior to PAP alone in elevating the arousal threshold, widening the CO2 reserve (primary outcome), and decreasing CSA indices. Specific Aim (2): To determine the effect of decreased peripheral chemoreceptor sensitivity on the propensity to CSA. The investigators hypothesize that combined PAP and supplemental O2 (targeting peripheral chemoreceptor sensitivity) will be superior to PAP alone in widening the CO2 reserve (primary outcome), reducing controller gain, and decreasing CSA indices. The proposed studies are innovative, testing mechanistic "PAP Plus" approach targeting underlying causes of CSA and alleviating upper airway obstruction with PAP. These studies will inform future clinical trials to transform central apnea care in patients with heart failure.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- Specific Aim (1) is to determine the effect of decreasing respiratory arousals on the propensity to central sleep apnea (CSA). The investigators hypothesize that combined therapy with PAP and trazodone will be superior to PAP alone in elevating the arousal threshold, widening the CO2 reserve, and decreasing CSA indices. Specific Aim (2) is to determine the effect of decreased peripheral chemoreceptor sensitivity on the propensity to CSA. The investigators hypothesize that combined therapy with PAP and supplemental oxygen (O2) will be superior to positive airway pressure (PAP) alone in widening the carbon dioxide (CO2) reserve, reducing controller gain, and decreasing CSA indices.
| Arm | Type | Receives |
|---|---|---|
| Trazodone | Active comparator | Drug: Trazodone + positive airway pressure (PAP) therapyTo determine the effect of dampening respiratory arousals. The investigators hypothesize that positive airway pressure (PAP) therapy with trazodone at 100 milligrams will be superior to CPAP alone in widening the carbon dioxide (CO2) reserve during sleep, decreasing respiratory arousals, and increasing the arousal threshold. |
| Oxygen | Active comparator | Drug: Oxygen + positive airway pressure (PAP) therapyTo determine the effect of dampening peripheral chemoreceptor sensitivity. The investigators hypothesize that supplemental oxygen will be superior to CPAP alone in widening the carbon dioxide (CO2) reserve during sleep. The secondary analysis will use CAI as supplemental oxygen, which may obscure the detection of hypopneas based on desaturation. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Men and women Veterans with central sleep apnea, defined as Apnea Hypopnea Index (AHI)>15/hour with CAHI>5/hour, will be included with the experiments
- Those with chronic, stable heart failure with reduced ejection fraction, receiving stable optimized guideline-based therapy and no hospitalizations or change in the medical regimen for the past 90 days before enrollment
Key exclusion criteria (13 listed)
- Pregnant or breastfeeding females
- Moderate or severe obstructive or restrictive lung disease, including supplemental oxygen (O2) use
- Current treatment for central sleep apnea (CSA), including any form of positive airway pressure (PAP) in the past three months, or phrenic nerve situation
- Too ill to engage in the study procedures, inability to provide consent for participation
- A history of cardiac arrhythmia
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Trazodone + positive airway pressure (PAP) therapyThe central apnea index and the apneic threshold will be compared under two conditions: trazodone or placebo. In addition, participants will get PAP therapy during both the conditions. | Drug | Trazodone |
| Oxygen + positive airway pressure (PAP) therapyThe central apnea index and the apneic threshold will be compared under two conditions: oxygen or room air. In addition, participants will get PAP therapy during both the conditions. | Drug | Oxygen |
Primary outcome
Carbon dioxide (CO2) Reserve
Time frame: 120 days
CO2 reserve is the requisite change to induce central apnea to as the CO2 reserve, which can be positive or negative.
5 secondary outcomes
Peripheral Chemoresponsiveness
Time frame: 120 days
Arousal Threshold
Time frame: 120 days
Carotid body function
Time frame: 120 days
Controller gain
Time frame: 120 days
Plant gain
Time frame: 120 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Oct 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
M Safwan Badr, MD principal investigator
John D. Dingell VA Medical Center, Detroit, MI
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Trazodone + positive airway pressure (PAP) therapy and Oxygen + positive airway pressure (PAP) therapy in people with Sleep Disordered Breathing and Able Bodied, run by VA Office of Research and Development at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 13 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact M S Badr, MD ((313) 576-1000 ext. 65710, sbadr@med.wayne.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Carbon dioxide (CO2) Reserve (time frame: 120 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Oct 2026; AzTrials last refreshed its copy on 26 Oct 2026.