Optimal Dosage of Acetazolamide for OSA Treatment
- Registration Number
- NCT04726982
- Lead Sponsor
- University Hospital, Antwerp
- 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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 100
- AHI between 15 and 65 events/hour
- BMI < 35 kg/m²
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Craniofacial anomalies
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Central sleep apnea (defined as central AHI > 25% of total AHI)
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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
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Conditions likely to affect OSA physiology: neuromuscular disease or other major neurological disorders, heart failure, or any other unstable major medical condition.
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Intake of drugs that substantially stimulate or depress respiration, including benzodiazepines, opioids, theophylline, and pseudoephedrine
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Inadequately treated sleep disorders other than OSA that would confound functional sleep assessment
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Inability of the patient to understand and/or comply to the study procedures
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Active psychiatric disease (psychotic illness, major depression, anxiety attacks, alcohol or drug abuse)
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Pregnancy
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Matching placebo tablets. The drug should be taken one hour before bedtime. Total treatment duration will be 6 weeks. Low dose acetazolamide Acetazolamide Unembellished white tablets. The drug should be taken one hour before bedtime. Total treatment duration will be 6 weeks. High dose acetazolamide Acetazolamide Unembellished white tablets. The drug should be taken one hour before bedtime. Total treatment duration will be 6 weeks.
- Primary Outcome Measures
Name Time Method Apnea-hypopnea index (AHI) 4 weeks Change in AHI (events/hour) from baseline to follow-up. The AHI is a measure of sleep apnea severity that encompasses the frequency of apneas (cessations in breathing) and hypopneas (reductions in airflow).
- Secondary Outcome Measures
Name Time Method Percent responders 4 weeks Treatment response will be defined as a reduction in AHI of ≥ 50%.
Nocturnal oxygen saturation 4 weeks Change in mean and minimal SaO2 (%).
Oxygen desaturation index (ODI) 4 weeks Change in ODI (events/hour) from baseline to follow-up. The ODI represents the average number of desaturation episodes (≥ 3%) per hour sleep.
Lung function parameters 4 weeks Change in flow-volume curve from baseline to follow-up.
Sleep-related quality of life: Functional Outcome of Sleep Questionnaire (FOSQ-10) 6 weeks This questionnaire is an abbreviated version of the original 30-item version. The FOSQ-10 consists of 10 items that are distributed among 5 subscales: general productivity (2 items), activity level (3 items), vigilance (3 items), social outcomes (1 item), and intimacy and sexual relationships (1 item). The questionnaire has a 4-point scale. The total score is calculated as the sum of the subscale means and can range from 5 to 20. The minimal important difference ranges from 1.7 to 2.0 points.
Pathophysiological traits 4 weeks Changes in pathophysiological traits (Vpassive, Vactive, Arousal Threshold, Loop Gain) will be quantified as %Veupnea from polysomnography data using a validated algorithm.
Daytime sleepiness: Epworth Sleepiness Scale (ESS) 6 weeks The ESS asks respondents to rate on a 4-point scale (0-3) their usual chances of dozing off or falling asleep while engaged in eight different activities. The ESS score (the sum of 8 item scores) can range from 0 to 24. The higher the ESS score, the higher that person's sleep propensity in daily life. A score higher than 10 indicates the presence of excessive daytime sleepiness.
Snoring intensity: Visual Analogue Scale (VAS) 6 weeks A standard 10-point VAS ranging from 0 (no snoring) to 10 (extreme snoring) will be used to evaluate the subjective status of snoring during sleep. Heavy snoring corresponds to a snoring index of at least 7. A decrease of 3 points after treatment is considered significant. To be considered as an important reduction, snoring needs to reduce to an index that is no longer experienced as bothersome (i.e. \< 3).
Arterial blood gas measurements 4 weeks Change in pO2 (mmhg) and pCO2 (mmhg) from baseline to follow-up.
Trial Locations
- Locations (1)
Antwerp University Hospital
🇧🇪Edegem, Antwerp, Belgium