Effect of Acetazolamide on Postural Control in Patients With Respiratory Disease at Altitude

Study Overview
=================
Brief Summary
-----------------
In this trial, the investigators will evaluate the effect of acetazolamide (375 mg per day) vs. placebo on postural control at acute altitude exposure in patients with COPD.

Detailed Description
-----------------
This is a randomized, placebo-controlled, double-blind parallel trial evaluating the effect of acetazolamide (375 mg per day) vs. placebo on postural control at altitude (Tuja Ashu, 3200 m). 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. Randomization to acetazolamide or placebo will be carried out after baseline measurements in Bishkek (760 m). Postural control will be assessed by a rectangular, stable balance platform (Wii Balance Board) measuring the body's center of gravity. The movement of the body's center of gravity will be recorded in a two-dimensional coordinate system and indicated as path length.

Official Title
-----------------
Effect of Acetazolamide on Postural Control in Patients With Chronic Obstructive Pulmonary Disease at Altitude: A Randomized, Placebo-controlled, Double-blind Parallel Trial

Conditions
-----------------
Chronic Obstructive Pulmonary Disease

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


Participation Criteria
=================
Eligibility Criteria
-----------------
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
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in postural control | Difference in altitude-induced change (between day 2 at 760 meters a.s.l. vs. day 2 at 3200 meters a.s.l.) of center of gravity displacement between acetazolamide and placebo group, measured by a balance platform | Day 2 at 760m and 3200m | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in arterial oxygen saturation | Difference in altitude-induced change (between day 2 at 760 meters a.s.l. vs. day 2 at 3200 meters a.s.l.) of arterial oxygen saturation between acetazolamide and placebo group, measured by pulse oximetry | Day 2 at 760m and 3200m | 
| acute mountain sickness | Difference in acute mountain sickness severity on day 2 at 3200 meters a.s.l. between acetazolamide and placebo group, measured by the environmental symptoms questionnaire cerebral subscore | Day 2 at 3200m | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
postural control, balance performance, airway disease, altitude, prevention, acetazolamide