Recruiting

Drive-Dependent OSA

Sponsor:

Brigham and Women's Hospital

Code:

NCT06091098

Conditions

OSA

Eligibility Criteria

Sex: All

Age: 21 - 70+

Healthy Volunteers: Not accepted

Interventions

Dynamic CO2

Sham CO2

Study Details

Brief summary:

Obstructive sleep apnea (OSA) is a highly prevalent disorder that has major consequences for cardiovascular health, neurocognitive function, risk of traffic accidents, daytime sleepiness, and quality of life. For years, a "classic" model of OSA has been used to describe the disorder, which fails to capture it's complexity. Recently, a model for OSA called drive-dependent OSA was discovered be more prevalent in the OSA population. The drive-dependent subgroup benefits exclusively from increased ventilation, increased dilator muscle activity, and reduced event risk when drive spontaneously rises. This study seeks to provide direct evidence that reducing the loss of drive prevents the loss of ventilation, pharyngeal muscle activity, and thus the onset of OSA respiratory events, specifically in "drive-dependent" but not "classic" OSA. This will be achieved using CO2 delivered at precise times during breaths in sleep to prevent loss of overall ventilatory drive.

Conditions

OSA

Study ID

NCT06091098

Start date

Mar 27, 2024

Status verified date

Mar, 2025

Completion date

Dec 31, 2027

Anticipated

Primary completion date

Dec 1, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 21 - 70+

Healthy Volunteers: Not accepted

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.

Study Design

Enrollment

36 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Dynamic CO2 within Drive-Dependent OSA

During sleep, before \~30 distinct respiratory events, we will administer \~2% CO2 for \~3-4 breaths.

active comparator: Dynamic CO2 within Classic OSA

During sleep, before \~30 distinct respiratory events, we will administer \~2% CO2 for \~3-4 breaths.

sham comparator: Sham CO2 within Drive-Dependent OSA

During sleep, Sham CO2 (air) will be administered for \~3-4 breaths before respiratory events.

sham comparator: Sham CO2 within Classic OSA

During sleep, Sham CO2 (air) will be administered for \~3-4 breaths before respiratory events.

Interventions

Dynamic CO2

2% inspired CO2 for 2-4 breaths

Sham CO2

Air

Primary outcome measure

  • Reduction in odds of respiratory event [ Time Frame: 1 night ]

Central Contacts and Locations

Central contacts

Scott Sands, PhD

8579280341sasands@bwh.harvard.edu

Atqiya Aishah, PhD

aaishah@bwh.harvard.edu

Locations

Brigham and Women's Hospital

Recruiting

Boston, Massachusetts, United States, 02115

Contacts

Scott SANDS, PhD

sasands@partners.org

More Information

Sponsor

Brigham and Women's Hospital

Last update posted

Mar 19, 2025

Last verified

Mar, 2025

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Brigham and Women's Hospital on 2025-03-19.