Acetazolamide as a Means to Mitigate Falling Ventilatory Drive and Drive-dependent OSA
Brigham and Women's Hospital
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. This drive-dependent OSA is due to ventilation instability that occurs during respiratory events however these individuals have spontaneous increases in drive during respiratory events that stabilize their airway (i.e., via improving upper airway muscle activity) and reduce the risk of respiratory events in people with OSA. Therefore, by stabilizing the ventilatory drive, OSA should be treatable. Acetazolamide is a pharmacological ventilatory stimulant and has been previously shown to reduce OSA severity. As such in this study, the goal is to demonstrate acetazolamide improves OSA severity in 'drive-dependent' OSA people by improving drive-related pharyngeal obstructions compared to the 'classic' OSA people.
Description
The goal of this detailed randomized controlled mechanistic clinical study, with gold-standard measurements of ventilatory drive and dilator muscle activity, is to test the hypotheses that acetazolamide improves OSA in patients with (N=18) but not without (N=18) drive-dependent OSA (i.e. drive-dependent status explains treatment efficacy). We will also show that acetazolamide efficacy is explained by mitigating drive-related reduction in pharyngeal obstruction. A 4-wk open-label extension will explore repeated-dose efficacy without invasive measurements in both subgroups. Subjects will attend…
Eligibility
- Age range
- 21–80 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Ages 21-80 years * Suspected OSA (snoring, sleepiness, witnessed apneas, other clinical symptoms) or diagnosed OSA (severity not required) * Untreated; No use of OSA treatments within 2 weeks of the baseline study. No plans to start OSA treatments for the duration of the study protocol Exclusion Criteria: * Any unstable medical condition * Current use of the study medication. * Use of ventilatory stimulant or depressant medications that may complicated interpretation of results (including opioids, barbiturates, doxapram, almitrine, theophylline, 4-hydroxybutanoic acid)…
Interventions
- DrugAcetazolamide
Administered for 3 nights, half-dose (1 pill) on the first night followed by full dose (2x250mg pills) for 2 nights
- DrugPlacebo
Placebo sugar pills administered for 3 nights, half-dose (1 pill) on the first night followed by full dose (2 pills) for 2 nights
Location
- Brigham and Women's HospitalBoston, Massachusetts