Effect of Acetazolamide on Sleep Related Breathing Disturbances in Patients With Respiratory Disease at Altitude

Study Overview
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Brief Summary
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In this trial, the investigators will evaluate the effect of acetazolamide (375 mg per day) vs. placebo on sleep related breathing disturbances at altitude in patients with COPD.

Detailed Description
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This is a randomized, placebo-controlled, double-blind parallel trial evaluating the effect of acetazolamide (375 mg per day) vs. placebo on sleep related breathing disturbances in lowlanders with chronic obstructive pulmonary disease travelling to altitude. Participants living in the Bishkek area, Kyrgyzstan (760m), will be transferred by car within 4h to the Tuja Ashu high altitude clinic (3200 m), and stay there for 2 days. Acetazolamide 375mg/day (or placebo), will be administered 24 hours before departure at 760 m and during the stay at altitude. Outcomes will be assessed during the stay at 3200 m. Sleep related breathing disturbances will be evaluated by respiratory polygraphy. An interim analysis will be carried out when 90 patients will have completed the study or after the first year. The Peto's method will be used to correct the P-values.

Official Title
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Effect of Acetazolamide on Sleep Related Breathing Disturbances in Patients With Chronic Obstructive Pulmonary Disease at Altitude, Assessed by Respiratory Polygraphy: A Randomized, Placebo-controlled, Double-blind Parallel Trial

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: ACETAZOLAMIDE oral capsule
* Drug: Placebo oral capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients, age 18-75 yrs. COPD diagnosed according to GOLD, FEV1 40-80% predicted, SpO2 ≥92% at 750 m. Born, raised and currently living at low altitude (<800m). Written informed consent. Exclusion Criteria: COPD exacerbation, very severe COPD with hypoxemia at low altitude (FEV1/FVC <0.7, FEV1 <40% predicted, oxygen saturation on room air <92% at 750 m). Comorbidities such as uncontrolled cardiovascular disease, i.e., unstable systemic arterial hypertension, coronary artery disease; previous stroke; OSA; pneumothorax in the last 2 months. Internal, neurologic, rheumatologic or psychiatric disease including current heavy smoking (>20 cigarettes per day) Known renal failure or allergy to acetazolamide and other sulfonamides

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ACETAZOLAMIDE oral capsule<br>Acetazolamide 375mg/day (capsule @125 mg: 1 in the morning, 2 in the evening), orally. Medication starts 24 hours before ascent to 3200m until the morning after the second night at 3200m | Drug: ACETAZOLAMIDE oral capsule<br>* Administration of 125mg acetazolamide in the morning, 250mg in the evening, starting 24 hours before departure to 3200m<br>|
| Placebo Comparator: PLACEBO oral capsule<br>Placebo (capsules identically looking as acetazolamide capsules: 1 in the morning, 2 in the evening), orally. Medication starts 24 hours before ascent to 3200m until the morning after the second night at 3200m. | Drug: Placebo oral capsule<br>* Administration of equally looking placebo capsules in the morning and evening, starting 24 hours before departure to 3200m<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in nocturnal oxygen saturation | Difference in altitude-induced change in mean nocturnal oxygen saturation measured by pulse oximetry between acetazolamide and placebo group | night 1 at 760m and night 1 at 3200 m | 
| Change in nocturnal oxygen desaturation index | Difference in altitude-induced change in the mean number of cyclic dips in oxygen saturation measured by pulse oximetry between acetazolamide and placebo group | night 1 at 760m and night 1 at 3200 m | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in nocturnal oxygen saturation | Difference in altitude-induced change in mean nocturnal oxygen saturation measured by pulse oximetry between acetazolamide and placebo group | night 1 at 760m and night 2 at 3200 m | 
| Change in nocturnal oxygen desaturation index | Difference in altitude-induced change in the mean number of cyclic dips in oxygen saturation measured by pulse oximetry between acetazolamide and placebo group | night 1 at 760m and night 2 at 3200 m | 
| Change in apnea/hypopnea index | Difference in altitude-induced change in mean number of apneas/hypopneas per hour between the acetazolamide and placebo group | night 1 at 760m and night 1 at 3200 m | 
| Change in apnea/hypopnea index | Difference in altitude-induced change in mean number of apneas/hypopneas per hour between the acetazolamide and placebo group | night 1 at 760m and night 2 at 3200 m | 
| Change in subjective sleepiness and sleep quality | Difference in altitude-induced change in subjective sleepiness and sleep quality assessed by a visual analog scale between acetazolamide and placebo group | Day 1 and 2 at 760m and 3200m | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sleep related breathing disturbances, respiratory polygraphy, airway disease, emphysema, acetazolamide, altitude, nocturnal pulse oxymetry