Acetazolamide on REM OSA

NCT ID: NCT05589792

Last Updated: 2026-01-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-01-30
• Study Completion Date: 2025-12-31

Brief 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. 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.

Detailed Description

After a baseline home sleep test that will assess the presence of OSA and REM OSA, two overnight, in-lab sleep studies will be performed: a drug night and a placebo night. The patient will breath spontaneously (without CPAP) for both nights. On the study nights, subjects will present to the laboratory in the evening and be instrumented with a full polysomnigraphy for monitoring sleep, physiological variables (endotypes), and respiratory events. Participants will also be instrumented with EMG wires and introesophageal catheter for the recording of genioglossus muscle activity and respiratory drive, respectively. A history and physical examination will be performed on each night prior to beginning the study, as will a urine pregnancy test in premenopausal women. Acetazolamide 500 mg will be taken for 2 days (including the day of the study), after a day in which it will be administered at half dose, before bedtime. Subjects will sleep at least 50% of the night in the supine position. At least four hours of sleep with high quality signal acquisition will be required for a study to be judged adequate. Subjective sleep quality will be assessed in the morning. After the first overnight study is completed, there will be a four day washout period prior to crossing over to the other treatment

Conditions

Obstructive Sleep Apnea

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

Placebo capsule before bedtime for 3 nights before the studies (inclusive)

Group Type: PLACEBO_COMPARATOR

Placebo oral capsule

Intervention Type: DRUG

Placebo before sleep for 3 nights before the study (inclusive)

Acetazolamide

Acetazolamide 250 mg before bedtime 3 nights before the study, Acetazolamide 500 mg before bedtime for 2 nights before the study (inclusive)

Group Type: ACTIVE_COMPARATOR

Acetazolamide

Intervention Type: DRUG

Acetazolamide 250 mg 3 nights before the study at bedtime, Acetazolamide 500 mg for 2 nights before the study (inclusive) at bedtime.

Interventions

Placebo oral capsule

Placebo before sleep for 3 nights before the study (inclusive)

Intervention Type: DRUG

Acetazolamide

Acetazolamide 250 mg 3 nights before the study at bedtime, Acetazolamide 500 mg for 2 nights before the study (inclusive) at bedtime.

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Brigham and Women's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Ludovico Messineo

Instructor in medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Brigham and Women's Hospital

Boston, Massachusetts, United States

Countries

United States

Other Identifiers

2022p002458

Identifier Type: -

Identifier Source: org_study_id