Investigating the effects of CO2 on obstructive sleep apnea

Reversible Effect of Falling Ventilatory Drive in Drive-dependent OSA

This study is testing if giving CO2 during sleep can help people with obstructive sleep apnea breathe better and reduce their sleep apnea events.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 36 (estimated)
• Ages: 21 Years to 80 Years
• Sex: All
• Sponsor: Brigham and Women's Hospital (other)
• Locations: 1 site (Boston, Massachusetts)
• Trial ID: NCT06091098 on ClinicalTrials.gov

What this trial studies

This study focuses on obstructive sleep apnea (OSA), particularly a newly identified subgroup known as drive-dependent OSA. It aims to provide evidence that administering CO2 at specific times during sleep can prevent the decline in ventilatory drive, thereby reducing the occurrence of OSA events. Participants will undergo a series of assessments, including a baseline sleep study and an overnight physiological intervention, to measure the impact of CO2 on ventilatory drive and upper airway muscle activity. The study will involve both patients diagnosed with OSA and those suspected of having it, using advanced physiological measurements to evaluate outcomes.

Who should consider this trial

Good fit: Ideal candidates include individuals diagnosed with obstructive sleep apnea or those suspected of having it, who can temporarily withhold their current treatments.

Not a fit: Patients with unstable medical conditions or those on medications that depress ventilatory drive may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve the management of obstructive sleep apnea, particularly for those with drive-dependent characteristics.

How similar studies have performed: While the approach of using CO2 to mitigate ventilatory drive is novel, similar studies have shown promise in understanding and treating OSA.

Eligibility criteria

Inclusion Criteria:

* Diagnosed OSA (AHI≥15 events/h reported in a PSG performed within 1 year) or Suspected OSA (snoring, sleepiness, witnessed apneas, other clinical symptoms)
* Use of CPAP or other therapies is acceptable; individuals will be asked to withhold treatment for 3 days before each study visit. Individuals who are occupational drivers or operate heavy machinery will not be asked to withhold treatment.

Exclusion Criteria:

* Any unstable medical conditions
* Conditions that could meaningfully raise the cardiovascular risks of brief low-dose hypercapnic-hypoxic inspired gas mixture: heart failure (LVEF\<45% if known), recent cardiovascular event (\<12 mo), recent cerebrovascular event (\<12 mo)\*
* Medications known to depress ventilatory drive (e.g. opioids, barbiturates)
* Conditions likely to increase arousability from sleep: insomnia
* Other sleep disorders that may complicate establishment of sleep: periodic limb movements (periodic limb movement arousal index \> 10/hr), narcolepsy, or parasomnias
* For intramuscular electrodes and catheter: allergy to lidocaine
* Highly-sensitive gag reflex. Patients with a self-reported 'highly-sensitive gag reflex', including an affirmative response to 'Do you sometimes gag when brushing your teeth?', will not take part in the physiology studies given the placement of an esophageal catheter
* For intramuscular electrodes: use of aspirin or other oral anti-platelets / anti-coagulants
* For oronasal mask: severe claustrophobia
* Pregnancy or nursing

  * We do not intend to exclude patients with controlled cardiovascular disease (hypertension of any severity, arrhythmias, stents) common in the OSA patient population. The transient gas mixture interventions are mild, short-lived, and act to slow the spontaneous recovery of blood gas levels to prevent cyclic upper airway obstruction as opposed to exacerbating them. Control of breathing studies commonly increase inspired CO2/reduce inspired oxygen (using higher concentrations via rebreathing tests for longer durations) in patients with a range of comorbidities including heart failure. The level of hypercapnic-hypoxia used is equivalent to taking slightly smaller breaths (by about a third, for the standard dose gas mixture 2%CO2/18.5%O2) for several breaths, or skipping a breath (for the highest dose gas mixture 6%CO2/14%O2), physiological changes that typically cause no noticeable oxygen desaturation, and are minimal compared with the effects of the larger ventilation reduction that accompanies OSA.

Where this trial is running

Boston, Massachusetts

• Brigham and Women's Hospital — Boston, Massachusetts, United States (RECRUITING)

Study contacts

• Principal investigator: Scott Sands, PhD — Brigham and Women's Hospital and Harvard Medical School
• Study coordinator: Scott Sands, PhD

Conditions: OSA