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

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

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.

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.

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

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.

Administration of 125mg acetazolamide in the morning, 250mg in the evening, starting 24 hours before departure to 3200m

Administration of equally looking placebo capsules in the morning and evening, starting 24 hours before departure to 3200m

Difference in altitude-induced change in directional error between acetazolamide and placebo group, measured by the motor task manager

Difference in altitude-induced change of arterial oxygen saturation between acetazolamide and placebo group, measured by pulse oxymetry

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

Scheiwiller PM, Furian M, Buergin A, Mayer LC, Schneider SR, Mademilov M, Lichtblau M, Muralt L, Sheraliev U, Sooronbaev TM, Ulrich S, Bloch KE. Visuomotor performance at high altitude in COPD patients. Randomized placebo-controlled trial of acetazolamide. Front Physiol. 2022 Sep 8;13:980755. doi: 10.3389/fphys.2022.980755. eCollection 2022.