Recruiting

Phase 4

PAP with Pharmacological AgentCentral Apnea in Heart Failure: Physiological Mechanisms to Inform Treatment

Sponsor:

VA Office of Research and Development

Code:

NCT07210606

Conditions

Sleep Disordered Breathing

Able Bodied

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Accepted

Interventions

Trazodone + positive airway pressure (PAP) therapy

Oxygen + positive airway pressure (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

NCT07210606

Start date

Sep 16, 2026

Status verified date

Oct, 2026

Completion date

Dec 31, 2030

Anticipated

Primary completion date

Jun 30, 2030

Anticipated

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 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

Exclusion Criteria:

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
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

Study Design

Enrollment

200 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

active comparator: Trazodone

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.

active comparator: Oxygen

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.

Interventions

Trazodone + positive airway pressure (PAP) therapy

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) therapy

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.

Primary outcome measure

Carbon dioxide (CO2) Reserve [ Time Frame: 120 days ]

Central Contacts and Locations

Central contacts

M S Badr, MD

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

Locations

John D. Dingell VA Medical Center, Detroit, MI

Recruiting

Detroit, Michigan, United States, 48201-1916

Contacts

M S Badr, MD

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

Lynn M Huber

(313) 576-3106 lynn.huber@va.gov

Principal Investigator:

M Safwan Badr, MD

More Information

Sponsor

VA Office of Research and Development

Last update posted

Oct 13, 2026

Last verified

Oct, 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
Cheyne Stokes Breathing (CSB)
Carotid Body Function
Peripheral Chemoresponsiveness
Heart Failure

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-14. This information was provided to ClinicalTrials.gov by VA Office of Research and Development on 2026-10-13. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.