HighCycle Study: Effect of Acetazolamide on Acute Mountain Sickness in Women Compared to Men
NCT Number: NCT06499727
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE4
Conditions: Acute Mountain Sickness
Interventions: DRUG: Acetazolamide|DRUG: Placebo
Sponsor: University of Zurich
Collaborators: National Center of Cardiology and Internal Medicine named after academician M.Mirrakhimov|University Hospital Heidelberg|Laboratoire des Adaptations Métaboliques à l'Exercice en conditions Physiologiques et Pathologiques
Sex: ALL
Age: ADULT
Enrollment: 270
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: QUADRUPLE (PARTICIPANT, CARE_PROVIDER, INVESTIGATOR, OUTCOMES_ASSESSOR)|Primary Purpose: PREVENTION
Start Date: 2024-07-15
Completion Date: 2025-12-31
Locations: National Center for Cardiology and Internal Medicine, Bishkek, 720040, Kyrgyzstan

Summary:
Millions of people travel to high altitude for work or leisure activities and are exposed to reduced inspiratory oxygen partial pressure and hypoxemia that may lead to altitude illness, among which the most common form is acute mountain sickness (AMS). The main AMS symptoms are headache, malaise, weakness, and fatigue. Prospective studies have shown that 20-60% of newcomers at 2500-4000m develop AMS requiring them to take medications, while, at very high altitudes, AMS may progress to high altitude cerebral oedema. Whether women are more susceptible to AMS remains insufficiently understood since no prospective study controlled for sex hormones, use of hormone contraception or assessed menstrual cycle phase (MCP) at altitude. Therefore, women remain underrepresented and poorly characterized in high altitude studies. In addition, the efficacy and safety of 250 mg/day acetazolamide, the standard recommendation for AMS prevention, has never been compared between sexes, although, women have presumably higher acetazolamide plasma concentration due to lower blood volume. Given the known dose-dependent preventive but also side effects of acetazolamide and equal proportion of women and men among mountain travellers, there is an urgent need to conclusively quantify the efficacy and safety of pre-ventive acetazolamide therapy against AMS in women compared to men.

Primary Outcome Measures: Acute Mountain Sickness (AMS) Incidence, LLS 2018, Sex-related difference between acetazolamide and placebo group in the incidence of AMS. AMS incidence will be defined as a Lake Louise Questionnaire version 2018 score of ≥3., Day 1 to 3 at 3600 m
Secondary Outcome Measures: Acute Mountain Sickness (AMS) Incidence, LLS 1993, Sex-related difference between acetazolamide and placebo group in the incidence of AMS. AMS incidence will be defined as a Lake Louise Questionnaire version 1993 score of ≥3., Day 1 to 3 at 3600 m|Acute Mountain Sickness (AMS) Severity, LLS 2018, Sex-related difference between acetazolamide and placebo group in the AMS severity assessed by the Lake Louise Questionnaire version 2018., Day 1 to 3 at 3600 m|Acute Mountain Sickness (AMS) Severity, LLS 1993, Sex-related difference between acetazolamide and placebo group in the AMS severity assessed by the Lake Louise Questionnaire version 1993., Day 1 to 3 at 3600 m|Drug-related side effects, Sex-related difference between acetazolamide and placebo group in the incidence and severity of medication side effects., Day 1 to 3 at 3600 m|Arterial blood gases, Sex-related differences between acetazolamide and placebo group in the arterial blood gases (pH, PaO2, PaCO2, SaO2)., Day 2 at 760 m and day 2 at 3600 m|Acetazolamide plasma concentration, Sex-related differences between acetazolamide plasma concentration assessed by dried blood spots., Day 2 at 3600 m|Hypoxic ventilatory response, Sex-related difference in the hypoxic ventilatory response assessed under FiO2 of 0.115 and while cycling on a bicycle at 30% of predicted maximal work capacity., Day 2 at 760 m|Perceived pain visualization, Sex-related differences between acetazolamide and placebo group on perceived pain sensations, visualized by the SMaRT tablet app, Day 1 to 3 at 3600 m