Recruiting
Phase 1
Phase 2

Acetazolamide

Sponsor:

Brigham and Women's Hospital

Code:

NCT06091085

Conditions

OSA

Eligibility Criteria

Sex: All

Age: 21 - 70+

Healthy Volunteers: Not accepted

Interventions

Acetazolamide

Placebo

Study Details

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. 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.

Conditions

OSA

Study ID

NCT06091085

Start date

Jan 31, 2024

Status verified date

Mar, 2024

Completion date

Dec 31, 2027

Anticipated

Primary completion date

Dec 1, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 21 - 70+

Healthy Volunteers: Not accepted

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).
  • Contraindications for acetazolamide, including:
  • Allergies to sulfonamides - e.g. acetazolamide, hydrochlorothiazide, furosemide, sulfasalazine, celecoxib, sumatriptan, and zonisamide.
  • closed-angle glaucoma
  • adrenal insufficiency
  • known electrolyte or acid/base imbalance (hyponatremia, hypokalemia, hyperchloremia, metabolic acidosis, acidemia)
  • clinically-significant kidney disorders (eGFR<60 ml/min/1.73m2)
  • clinically-significant liver disorders
  • Use of more than 500 mg/day of Aspirin, due to the potential for an interaction of acetazolamide and very high doses of Aspirin (acetylsalicylic acid, a salicylate drug)
  • Adrenocortical insufficiency
  • Low sodium or potassium
  • hyperchloremic acidosis
  • Conditions likely to affect obstructive sleep apnea physiology: neuromuscular disease or other major neurological disorder, heart failure, or any other unstable major medical condition.
  • Respiratory disorders other than obstructive sleep apnea:
  • central sleep apnea (>75% of respiratory events scored as central)
  • chronic hypoventilation/hypoxemia (awake SaO2 < 92% by oximetry) due to chronic obstructive pulmonary disease or other respiratory conditions
  • 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

Study Design

Enrollment

36 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Acetazolamide

Acetazolamide administered for 3 nights, half-dose (1 pill) on the first night followed by full dose (2x250mg pills) for 2 nights

placebo comparator: Placebo

Placebo sugar pills administered for 3 nights, half-dose (1 pill) on the first night followed by full dose (2 pills) for 2 nights

Interventions

Acetazolamide

Administered for 3 nights, half-dose (1 pill) on the first night followed by full dose (2x250mg pills) for 2 nights

Placebo

Placebo sugar pills administered for 3 nights, half-dose (1 pill) on the first night followed by full dose (2 pills) for 2 nights

Primary outcome measure

  • Percentage reduction of apnea-hypopnea Index (AHI) with active versus placebo therapy in drive-dependent vs classic OSA groups [ Time Frame: 1 night ]

Central Contacts and Locations

Central contacts

Scott Sands, PhD

8579280341sasands@bwh.harvard.edu

Atqiya Aishah, PhD

aaishah@bwh.harvard.edu

Locations

Brigham and Women's Hospital

Recruiting

Boston, Massachusetts, United States, 02141

Contacts

Scott A Sands, PhD

857-928-0341sasands@bwh.harvard.edu

More Information

Sponsor

Brigham and Women's Hospital

Last update posted

Mar 4, 2024

Last verified

Mar, 2024

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Brigham and Women's Hospital on 2024-03-04.