Effect of Acetazolamide on Cognition in Patients With Respiratory Disease at Altitude

Study Overview
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Brief Summary
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Randomized, placebo controlled trial evaluating the effect of acetazolamide on cognition in lowlanders with chronic obstructive pulmonary disease travelling from 760 m to 3200 m.

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 visuomotor learning performance at altitude (Tuja Ashu, 3200 m). Randomization to acetazolamide or placebo will be carried out after baseline measurements in Bishkek (760 m). Visuomotor learning performance will be tested by Motor Task Manager (MTM). The MTM requires the subjects to reach visual targets with a hand-held cursor. During progression of the test, the movement direction from the cursor on the computer screen will increasingly differ from the direction of the hand movement, forcing the unaware subject to implicitly adapt to the imposed cursor rotation. This test assesses a subjects ability to visuomotor adaption, perception and attention. Furthermore, as the task will be performed in the evening and after sleep in the next morning, the investigators will be able to assess overnight improvement of implicit learned skills.

Official Title
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Effect of Acetazolamide on Visuomotor Learning Performance in Patients With Chronic Obstructive Pulmonary Disease at Altitude

Conditions
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Chronic Obstructive Pulmonary Disease (COPD)

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 |
| --- | --- | --- |
| visuomotor learning performance, drug effect | Difference in altitude-induced change in directional error between acetazolamide and placebo group, measured by the motor task manager | Day 2 at 760m and 3200m | 
| visuomotor learning performance, altitude effect | Difference in directional error between 760 m and 3200 m altitude in placebo group | Day 1 and 2 at 760 m and at 3200m | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| arterial oxygen saturation | Difference in altitude-induced change of arterial oxygen saturation between acetazolamide and placebo group, measured by pulse oxymetry | Day 1 and 2 at 760 m and at 3200m | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cognition, visuomotor learning, airway disease, altitude, prevention, acetazolamide