Clinical trial NCT04726982: Optimal Dosage of Acetazolamide for OSA Treatment
Official title: Optimal Dosage of Acetazolamide for Obstructive Sleep Apnea Treatment: a Parallel-group, Double-blind, Placebo-controlled, Randomized Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Obstructive Sleep Apnea
Keywords: Carbonic anhydrase inhibitor
Treatment
Pharmacotherapy
Sleep apnea
Loop gain
Respiration
Ventilatory control instability
Acidosis
Lead sponsor: University Hospital, Antwerp
Sponsor class: OTHER
First posted: 2021-01-27
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Acetazolamide, a carbonic anhydrase inhibitor, has received some attention as potential treatment for obstructive sleep apnea (OSA). It produces a metabolic acidosis by excreting bicarbonate, thereby stimulating baseline ventilation. Evidence suggests that acetazolamide primarily improves ventilatory control instability (expressed as loop gain), which is an important contributor to the pathophysiology of OSA.

Few studies have assessed the efficacy of acetazolamide in patients with OSA. Since most of them had a small sample size and used different therapeutic dosages, clinical applications are currently limited. Therefore, this study aims to compare the effect of two acetazolamide dosages on the severity and pathophysiology of OSA.

Detailed description: In this double-blind, parallel-group, controlled trial, eligible patients will be randomized into one of the following treatment arms: (1) placebo, (2) 250 mg of acetazolamide, or (3) 500 mg of acetazolamide. After 4 weeks, treatment outcome will be assessed by in-laboratory polysomnography. Additionally, arterial blood gas analysis and lung function tests will be performed before and during treatment.

Eligibility criteria: Inclusion Criteria:

* AHI between 15 and 65 events/hour
* BMI \< 35 kg/m²

Exclusion Criteria:

* Craniofacial anomalies
* Central sleep apnea (defined as central AHI \> 25% of total AHI)
* Contra-indications related to acetazolamide treatment

  * Hypersensitivity to sulphonamides or acetazolamide
  * Renal impairment, electrolyte imbalances, and/or adrenocortical insufficiency
  * Clinically significant metabolic, hepatic, and/or hematological disease
  * Chronic obstructive pulmonary disease
  * Closed-angle glaucoma
* Conditions likely to affect OSA physiology: neuromuscular disease or other major neurological disorders, heart failure, or any other unstable major medical condition.
* Intake of drugs that substantially stimulate or depress respiration, including benzodiazepines, opioids, theophylline, and pseudoephedrine
* Inadequately treated sleep disorders other than OSA that would confound functional sleep assessment
* Inability of the patient to understand and/or comply to the study procedures
* Active psychiatric disease (psychotic illness, major depression, anxiety attacks, alcohol or drug abuse)
* Pregnancy

Primary outcomes:
measure: Apnea-hypopnea index (AHI)
timeFrame: 4 weeks
Secondary outcomes:
measure: Pathophysiological traits
timeFrame: 4 weeks
measure: Percent responders
timeFrame: 4 weeks
measure: Nocturnal oxygen saturation
timeFrame: 4 weeks
measure: Oxygen desaturation index (ODI)
timeFrame: 4 weeks
measure: Arterial blood gas measurements
timeFrame: 4 weeks
measure: Lung function parameters
timeFrame: 4 weeks
measure: Daytime sleepiness: Epworth Sleepiness Scale (ESS)
timeFrame: 6 weeks
measure: Sleep-related quality of life: Functional Outcome of Sleep Questionnaire (FOSQ-10)
timeFrame: 6 weeks
measure: Snoring intensity: Visual Analogue Scale (VAS)
timeFrame: 6 weeks
Other outcomes:
measure: Incidence of adverse events
timeFrame: 6 weeks
Locations:
city: Edegem
country: Belgium
facility: Antwerp University Hospital
state: Antwerp
Study officials:
affiliation: University Hospital, Antwerp
name: Olivier Vanderveken, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: