Effect of Acetazolamide on Sleep Disordered Breathing in Lowlanders Older Than 40 Years at Altitude

Study Overview
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Brief Summary
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Randomized, placebo controlled trial evaluating the effect of acetazolamide on sleep disordered breathing in lowlanders older than 40 years travelling from 760 m to 3'100 m.

Detailed Description
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This is a randomized, placebo-controlled, double-blind parallel trial evaluating the effect of preventive acetazolamide intake on the sleep disordered breathing in lowlanders older than 40 years 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 (3'100 m), and stay there for 2 days. Acetazolamide 375mg/day (or placebo), will be administered before departure at 760 m and during the stay at altitude. Outcomes will be assessed during the stay at 3'100 m. An interim analysis will be carried out when 80 participants will have completed the study or after the first year. The Peto's method will be used and the trial will be stopped when pre-specified futility boundaries were crossed.

Official Title
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Effect of Acetazolamide on Sleep Disordered Breathing in Lowlanders Older Than 40 Years at Altitude: A Randomized, Placebo-controlled, Double-blind Parallel Trial

Conditions
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Altitude Hypoxia

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: Healthy men and women, age 40-75 yrs, without any disease and need of medication. Born, raised and currently living at low altitude (<800m). Written informed consent. Kyrgyz ethnicity Exclusion Criteria: Any active respiratory, cardiovascular or other disease requiring regular treatment or being otherwise relevant for tolerance of hypoxia or altitude exposure. Any condition that may interfere with protocol compliance including current heavy smoking (>20 cigarettes per day or >20 pack-years with active smoking during the last 10 years), regular use of alcohol. Allergy to acetazolamide and other sulfonamides.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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 3'100m until the morning after the second night at 3'100m | Drug: ACETAZOLAMIDE oral capsule<br>* Administration of 1x125mg acetazolamide in the morning, 2x125mg in the evening, starting 24 hours before departure to 3'100m<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 3'100m until the morning after the second night at 3'100m | Drug: Placebo oral capsule<br>* Administration of equally looking placebo capsules in the morning and evening, starting 24 hours before departure to 3'100m<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 3'100 m | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in nocturnal oxygen saturation night 1 at 3'100m | 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 3'100 m | 
| Change in nocturnal oxygen saturation night 2 at 3'100m | 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 3'100 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 3'100 m | 
| Change in apnea/hypopnea index night 1 at 3'100m | 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 3'100 m | 
| Change in apnea/hypopnea index night 2 at 3'100m | 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 3'100 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 3'100m | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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healthy participants older than 40 years, sleep disordered breathing, periodic breathing, prevention, acetazolamide