Back to resultsOptimal Dosage of Acetazolamide for OSA Treatment
Primary Purpose
Obstructive Sleep Apnea
Status
Unknown status
Phase
Phase 4
Locations
Belgium
Study Type
Interventional
Intervention
Acetazolamide
Acetazolamide
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Obstructive Sleep Apnea focused on measuring Carbonic anhydrase inhibitor, Treatment, Pharmacotherapy, Sleep apnea, Loop gain, Respiration, Ventilatory control instability, Acidosis
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
Sites / Locations
- Antwerp University HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
Low dose acetazolamide
High dose acetazolamide
Placebo
Arm Description
Unembellished white tablets. The drug should be taken one hour before bedtime. Total treatment duration will be 6 weeks.
Unembellished white tablets. The drug should be taken one hour before bedtime. Total treatment duration will be 6 weeks.
Matching placebo tablets. The drug should be taken one hour before bedtime. Total treatment duration will be 6 weeks.
Outcomes
Primary Outcome Measures
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).
Secondary Outcome Measures
Pathophysiological traits
Changes in pathophysiological traits (Vpassive, Vactive, Arousal Threshold, Loop Gain) will be quantified as %Veupnea from polysomnography data using a validated algorithm.
Percent responders
Treatment response will be defined as a reduction in AHI of ≥ 50%.
Nocturnal oxygen saturation
Change in mean and minimal SaO2 (%).
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.
Arterial blood gas measurements
Change in pO2 (mmhg) and pCO2 (mmhg) from baseline to follow-up.
Lung function parameters
Change in flow-volume curve from baseline to follow-up.
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.
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.
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).
Full Information
NCT ID
NCT04726982
First Posted
January 26, 2021
Last Updated
May 17, 2021
Sponsor
University Hospital, Antwerp
1. Study Identification
Unique Protocol Identification Number
NCT04726982
Brief Title
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
2. Study Status
Record Verification Date
May 2021
Overall Recruitment Status
Unknown status
Study Start Date
April 20, 2021 (Actual)
Primary Completion Date
August 2022 (Anticipated)
Study Completion Date
December 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Antwerp
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obstructive Sleep Apnea
Keywords
Carbonic anhydrase inhibitor, Treatment, Pharmacotherapy, Sleep apnea, Loop gain, Respiration, Ventilatory control instability, Acidosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare Provider
Allocation
Randomized
Enrollment
100 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Low dose acetazolamide
Arm Type
Experimental
Arm Description
Unembellished white tablets. The drug should be taken one hour before bedtime. Total treatment duration will be 6 weeks.
Arm Title
High dose acetazolamide
Arm Type
Experimental
Arm Description
Unembellished white tablets. The drug should be taken one hour before bedtime. Total treatment duration will be 6 weeks.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Matching placebo tablets. The drug should be taken one hour before bedtime. Total treatment duration will be 6 weeks.
Intervention Type
Drug
Intervention Name(s)
Acetazolamide
Other Intervention Name(s)
Diamox, ATC code: S01EC01
Intervention Description
250 mg once daily
Intervention Type
Drug
Intervention Name(s)
Acetazolamide
Other Intervention Name(s)
Diamox, ATC code: S01EC01
Intervention Description
500 mg once daily
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Once daily
Primary Outcome Measure Information:
Title
Apnea-hypopnea index (AHI)
Description
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).
Time Frame
4 weeks
Secondary Outcome Measure Information:
Title
Pathophysiological traits
Description
Changes in pathophysiological traits (Vpassive, Vactive, Arousal Threshold, Loop Gain) will be quantified as %Veupnea from polysomnography data using a validated algorithm.
Time Frame
4 weeks
Title
Percent responders
Description
Treatment response will be defined as a reduction in AHI of ≥ 50%.
Time Frame
4 weeks
Title
Nocturnal oxygen saturation
Description
Change in mean and minimal SaO2 (%).
Time Frame
4 weeks
Title
Oxygen desaturation index (ODI)
Description
Change in ODI (events/hour) from baseline to follow-up. The ODI represents the average number of desaturation episodes (≥ 3%) per hour sleep.
Time Frame
4 weeks
Title
Arterial blood gas measurements
Description
Change in pO2 (mmhg) and pCO2 (mmhg) from baseline to follow-up.
Time Frame
4 weeks
Title
Lung function parameters
Description
Change in flow-volume curve from baseline to follow-up.
Time Frame
4 weeks
Title
Daytime sleepiness: Epworth Sleepiness Scale (ESS)
Description
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.
Time Frame
6 weeks
Title
Sleep-related quality of life: Functional Outcome of Sleep Questionnaire (FOSQ-10)
Description
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.
Time Frame
6 weeks
Title
Snoring intensity: Visual Analogue Scale (VAS)
Description
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).
Time Frame
6 weeks
Other Pre-specified Outcome Measures:
Title
Incidence of adverse events
Description
Safety and tolerability of study treatment.
Time Frame
6 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
79 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Eli Van de Perck, MD
Phone
38214244
Ext
+32
Email
eli.vandeperck@uza.be
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Olivier Vanderveken, MD, PhD
Organizational Affiliation
University Hospital, Antwerp
Official's Role
Principal Investigator
Facility Information:
Facility Name
Antwerp University Hospital
City
Edegem
State/Province
Antwerp
ZIP/Postal Code
2650
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eli Van de Perck, MD
First Name & Middle Initial & Last Name & Degree
Olivier Vanderveken, MD, PhD
12. IPD Sharing Statement
Plan to Share IPD
No
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Optimal Dosage of Acetazolamide for OSA Treatment
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