Reversible Effect of Falling Ventilatory Drive in Drive-dependent OSA

NCT06091098 | Recruiting

• 1 other identifier: 2023P002401
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Reduction in odds of respiratory event

  Active versus sham ventilatory drive intervention, difference between drive-dependent OSA and classic OSA subgroups

  1 night

Secondary Outcomes (5)

• Reduction in odds of respiratory event per unit increase in ventilatory drive

  1 night

• Increase in ventilation

  1 night

• Increase in ventilation per unit increase in ventilatory drive

  1 night

• Increase in peak genioglossus muscle activity

  1 night

• Increase in peak genioglossus muscle activity per unit increase in ventilatory drive

  1 night

Study Arms (4)

Dynamic CO2 within Drive-Dependent OSA

EXPERIMENTAL

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

Other: Dynamic CO2

Dynamic CO2 within Classic OSA

ACTIVE COMPARATOR

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

Other: Dynamic CO2

Sham CO2 within Drive-Dependent OSA

SHAM COMPARATOR

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

Other: Sham CO2

Sham CO2 within Classic OSA

SHAM COMPARATOR

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

Other: Sham CO2

Interventions

Dynamic CO2 OTHER

2% inspired CO2 for 2-4 breaths

Dynamic CO2 within Classic OSA; Dynamic CO2 within Drive-Dependent OSA

Sham CO2 OTHER

Air

Sham CO2 within Classic OSA; Sham CO2 within Drive-Dependent OSA

Eligibility Criteria

• Age: 21 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Brigham and Women's Hospital: lead

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

Study Officials

• Scott Sands, PhD

  Brigham and Women's Hospital and Harvard Medical School

  PRINCIPAL INVESTIGATOR

• Dillon Gilbertson

  Brigham and Women's Hospital and Harvard Medical School

  STUDY DIRECTOR

Central Study Contacts

Scott Sands, PhD

CONTACT

8579280341; sasands@bwh.harvard.edu

Atqiya Aishah, PhD

CONTACT

aaishah@bwh.harvard.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: This study is a mechanistic physiology study, employing unblinded within-night sham-controlled dynamic interventions to examine OSA pathophysiology Two groups of patients with classic OSA (n=18) and with drive-dependent (n=18)

Study Record Dates

• First Submitted: October 16, 2023
• First Posted: October 19, 2023
• Study Start: March 27, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: March 19, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Deidentified data will be shared freely with collaborating scientists at any time and more broadly to other scientists 12 months following all planned publications using the data.
• Access Criteria: Requests should be made in writing to the lead investigator.

Locations

US (1)