Acetazolamide as a Means to Mitigate Falling Ventilatory Drive and Drive-dependent OSA

Description

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

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Study Overview

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Study Details

Study overview

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.

Acetazolamide as a Means to Mitigate Falling Ventilatory Drive and Drive-dependent OSA

Acetazolamide as a Means to Mitigate Falling Ventilatory Drive and Drive-dependent OSA

Condition
OSA
Intervention / Treatment

-

Contacts and Locations

Boston

Brigham and Women's Hospital, Boston, Massachusetts, United States, 02141

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

For general information about clinical research, read Learn About Studies.

Eligibility 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
  • * 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

Ages Eligible for Study

21 Years to 80 Years

Sexes Eligible for Study

ALL

Accepts Healthy Volunteers

No

Collaborators and Investigators

Brigham and Women's Hospital,

Dillon Gilbertson, STUDY_DIRECTOR, Brigham and Women's Hospital and Harvard Medical School

Scott Sands, PhD, PRINCIPAL_INVESTIGATOR, Brigham and Women's Hospital and Harvard Medical School

Study Record Dates

2027-12-31