Central Sleep Apnea : Physiologic Mechanisms to Inform Treatment
Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age18+
SponsorVA Office of Research and Development
About this trial
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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
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
Disqualifiers
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,
Trial design
Design model
Crossover
Treatments tested in this trial
Acetazolamide + supplemental oxygen + PAP therapy
DrugEvery 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
DrugThe 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
DrugThe 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.
Treatment groups
200 Participants
are divided into 3 treatment groupsGroup A: acetazolamideActive comparator 1 intervention
Group B: zolpidemActive comparator 1 intervention
Group C: buspironeActive comparator 1 intervention
Trial outcomes
Primary outcomes
1
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 days2
Central apnea indices
Central apnea indices is used to indicate the severity of central sleep apnea
Time frame
120 daysSecondary outcomes
1
Controller gain
Controller gain is a ventilatory response to changes in end-tidal PCO2
Time frame
120 days2
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 days3
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 days4
Peripheral chemoreflex sensitivity
Peripheral chemoreflex sensitivity is measured either via brief hypoxia or a single breath of CO2.
Time frame
120 daysSponsors and contacts
Click on the lead sponsor to view all of their trials.
Source ClinicalTrials.gov