Acetazolamide on REM OSA

• Status: Not yet recruiting
• Trial end date: 2023-12-01
• Target enrollment: 0
• Participant gender: All

Summary

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. In particular, REM sleep is accompanied by more frequent and longer obstructive events, that yield more profound hypoxemia than during non-REM (nREM). Exaggerated OSA severity in REM is the consequence of ventilatory drive dips, particularly during phasic eye movements [18]. Unfortunately, the leading treatment for REM and nREM OSA, CPAP-which acts to pneumatically splint the pharynx open-is intolerable for many patients. Treatment outcomes for REM OSA are burdened by further incomplete CPAP adherence later in the night, which commonly leaves REM periods undertreated. In this protocol, the investigators will test the effect of Acetazolamide on REM OSA and on ventilatory parameters such as genioglossus muscle activity and ventilatory drive.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Brigham and Women's Hospital
• Treatments: Acetazolamide

Criteria

Inclusion Criteria:

• Diagnosed REM OSA (per baseline screening: REM AHI/nREM AHI≥2) [31-33]

• REM duration>10 minutes

• Not using CPAP (>1 week).

Exclusion Criteria:

• Any uncontrolled medical condition

• Current use of the medications under investigation

• Use of medications expected to stimulate or depress respiration (including opioids, barbiturates, doxapram, almitrine, theophylline, 4-hydroxybutanoic acid).

• Conditions likely to affect obstructive sleep apnea physiology: neuromuscular disease or other major neurological disorder, heart failure (also below), or any other unstable major medical condition.

• Respiratory disorders other than sleep disordered breathing:

chronic hypoventilation/hypoxemia (awake SaO2 < 92% by oximetry) due to chronic obstructive pulmonary disease or other respiratory conditions.

• Other sleep disorders: periodic limb movements (periodic limb movement arousal index > 10/hr), narcolepsy, or parasomnias.

• Contraindications for acetazolamide, including:

• Hyperchloremic acidosis

• Hypokalemia

• Hyponatremia

• Adrenal insufficiency

• Impaired kidney function

• Hypersensitivity to acetazolamide or other sulfonamides.

• Marked liver disease or impairment of liver function, including cirrhosis.

• Contraindications to the use of lidocaine 4%/oxymetazoline HCT.

• Claustrophobia

• Pregnancy or nursing