Acetazolamide on REM OSA

NCT05589792 | Completed Phase 1 FDA Drug

• 1 other identifier: 2022p002458
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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.

Conditions

Obstructive Sleep Apnea

Outcome Measures

Primary Outcomes (4)

• Apnea hypopnea index

  Number of events/hour of sleep

  1 night

• Hypoxic burden

  The total area under the respiratory event-related desaturation curve, measured as in %min/hr

  1 night

• Ventilatory drive in REM and NREM

  Ventilatory drive will be calculated using diaphragm EMG (as percent of eupneic ventilatory drive)

  1 night

• Genioglossus activity in REM and NREM

  Genioglossus activity will be calculated using EMG wires under the tongue (as percent of eupneic activity or maximal activity)

  1 night

Study Arms (2)

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo oral capsule

Acetazolamide

ACTIVE COMPARATOR

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

Drug: Acetazolamide

Interventions

Placebo oral capsule DRUG

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

Placebo

Acetazolamide DRUG

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

Acetazolamide

Eligibility Criteria

• Age: 21 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosed REM OSA (per baseline screening: REM AHI/nREM AHI≥2) \[31-33\]
• REM duration\>10 minutes
• Not using CPAP (\>1 week).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Brigham and Women's Hospital: lead

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Related Publications (1)

• Messineo L, Kim M, Azarbarzin A, Vena D, Preuss M, Esmaeili N, Aishah A, Lawrence NV, Gilbertson DC, White DP, Wellman A, Sands SA. Acetazolamide to prevent ventilatory drive withdrawal in REM sleep apnoea: a randomised controlled trial. Thorax. 2026 Mar 4:thorax-2025-223922. doi: 10.1136/thorax-2025-223922. Online ahead of print.

  PMID: 41781273 DERIVED

MeSH Terms

Conditions

Sleep Apnea, Obstructive

Interventions

Acetazolamide

Condition Hierarchy (Ancestors)

Sleep Apnea Syndromes; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Thiadiazoles; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Instructor in medicine

Study Record Dates

• First Submitted: October 18, 2022
• First Posted: October 21, 2022
• Study Start: January 30, 2023
• Primary Completion: December 1, 2025
• Study Completion: December 31, 2025
• Last Updated: January 20, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)