Optimal Dosage of Acetazolamide for OSA Treatment

Antwerp University Hospital (UZA)

Status and phase: Completed; Phase 4

Conditions: Obstructive Sleep Apnea

Treatments: Drug: Acetazolamide; Other: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT04726982

B3002021000015

Details and patient eligibility

About

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.

Full 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.

Enrollment: 91 patients

Sex: All

Ages: 18 to 79 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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91 participants in 3 patient groups, including a placebo group

Low dose acetazolamide

Experimental group

Description:

Unembellished white tablets. The drug should be taken one hour before bedtime. Total treatment duration will be 6 weeks.

Treatment:

Drug: Acetazolamide

Drug: Acetazolamide

High dose acetazolamide

Experimental group

Description:

Unembellished white tablets. The drug should be taken one hour before bedtime. Total treatment duration will be 6 weeks.

Treatment:

Drug: Acetazolamide

Drug: Acetazolamide

Placebo

Placebo Comparator group

Description:

Matching placebo tablets. The drug should be taken one hour before bedtime. Total treatment duration will be 6 weeks.

Treatment:

Other: Placebo