Optimal Dosage of Acetazolamide for OSA Treatment

Obstructive Sleep Apnea Clinical Trial

Official title:

Optimal Dosage of Acetazolamide for Obstructive Sleep Apnea Treatment: a Parallel-group, Double-blind, Placebo-controlled, Randomized Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04726982
• Other study ID #: B3002021000015
• Status: Recruiting
• Phase: Phase 4
• Start date: April 20, 2021
• Est. completion date: December 2022

Study information

• Verified date: May 2021
• Source: University Hospital, Antwerp
• Contact: Eli Van de Perck, MD
• Phone: 38214244
• Email: eli.vandeperck[@]uza.be
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 2022
• Est. primary completion date: August 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 79 Years

Eligibility

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

Related Conditions & MeSH terms

• Apnea
• Obstructive Sleep Apnea
• Sleep Apnea Syndromes
• Sleep Apnea, Obstructive

Intervention

Drug:
• Acetazolamide
250 mg once daily
• Acetazolamide
500 mg once daily

Other:
• Placebo
Once daily

Locations

Country	Name	City	State
Belgium	Antwerp University Hospital	Edegem	Antwerp

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Antwerp

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Incidence of adverse events	Safety and tolerability of study treatment.	6 weeks
Primary	Apnea-hypopnea index (AHI)	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).	4 weeks
Secondary	Pathophysiological traits	Changes in pathophysiological traits (Vpassive, Vactive, Arousal Threshold, Loop Gain) will be quantified as %Veupnea from polysomnography data using a validated algorithm.	4 weeks
Secondary	Percent responders	Treatment response will be defined as a reduction in AHI of = 50%.	4 weeks
Secondary	Nocturnal oxygen saturation	Change in mean and minimal SaO2 (%).	4 weeks
Secondary	Oxygen desaturation index (ODI)	Change in ODI (events/hour) from baseline to follow-up. The ODI represents the average number of desaturation episodes (= 3%) per hour sleep.	4 weeks
Secondary	Arterial blood gas measurements	Change in pO2 (mmhg) and pCO2 (mmhg) from baseline to follow-up.	4 weeks
Secondary	Lung function parameters	Change in flow-volume curve from baseline to follow-up.	4 weeks
Secondary	Daytime sleepiness: Epworth Sleepiness Scale (ESS)	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.	6 weeks
Secondary	Sleep-related quality of life: Functional Outcome of Sleep Questionnaire (FOSQ-10)	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.	6 weeks
Secondary	Snoring intensity: Visual Analogue Scale (VAS)	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).	6 weeks