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HighCycle Study: Effect of Acetazolamide on Acute Mountain Sickness in Women Compared to Men

Phase 4
Recruiting
Conditions
Acute Mountain Sickness
Interventions
Drug: Placebo
Registration Number
NCT06499727
Lead Sponsor
University of Zurich
Brief 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.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
270
Inclusion Criteria
  • Healthy, non-smoking men and women, age 18-44 years, without any disease and need of regular medication (including oral contraceptives).
  • BMI >18 kg/m2 and <30 kg/m2
  • Born, raised and currently living at altitudes <1000 m
  • Written informed consent
  • Premenopausal women with an eumenorrheic cycle
Exclusion Criteria
  • Other types of contraceptvies (contraceptives (hormonal intrauterine device, vaginal ring, subcutaneous injections or implants, among others)
  • Pregnancy or nursing
  • Anaemic (haemoglobin concentration <10g/dl)
  • Any altitude trip <4 weks before the study
  • Allergy to acetazolamide and other sulfonamides

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
WOMEN - PLACEBO oral capsulePlaceboPlacebo (capsules identically looking as acetazolamide capsules; 1 in the morning, 1 in the evening), orally. Medication starts 24 hours before ascent to 3600 m until the morning after the second night at 3600 m.
MEN - PLACEBO oral capsulePlaceboPlacebo (capsules identically looking as acetazolamide capsules; 1 in the morning, 1 in the evening), orally. Medication starts 24 hours before ascent to 3600 m until the morning after the second night at 3600 m.
WOMEN - ACETAZOLAMIDE oral capsuleAcetazolamideAcetazolamide 250 mg/day (capsules @125 mg; 1 in the morning, 1 in the evening), orally. Medication starts 24 hours before ascent to 3600 m until the morning after the second night at 3600 m.
MEN - ACETAZOLAMIDE oral capsuleAcetazolamideAcetazolamide 250 mg/day (capsules @125 mg; 1 in the morning, 1 in the evening), orally. Medication starts 24 hours before ascent to 3600 m until the morning after the second night at 3600 m.
Primary Outcome Measures
NameTimeMethod
Acute Mountain Sickness (AMS) Incidence, LLS 2018Day 1 to 3 at 3600 m

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.

Secondary Outcome Measures
NameTimeMethod
Acute Mountain Sickness (AMS) Incidence, LLS 1993Day 1 to 3 at 3600 m

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.

Acute Mountain Sickness (AMS) Severity, LLS 2018Day 1 to 3 at 3600 m

Sex-related difference between acetazolamide and placebo group in the AMS severity assessed by the Lake Louise Questionnaire version 2018.

Acute Mountain Sickness (AMS) Severity, LLS 1993Day 1 to 3 at 3600 m

Sex-related difference between acetazolamide and placebo group in the AMS severity assessed by the Lake Louise Questionnaire version 1993.

Drug-related side effectsDay 1 to 3 at 3600 m

Sex-related difference between acetazolamide and placebo group in the incidence and severity of medication side effects.

Arterial blood gasesDay 2 at 760 m and day 2 at 3600 m

Sex-related differences between acetazolamide and placebo group in the arterial blood gases (pH, PaO2, PaCO2, SaO2).

Acetazolamide plasma concentrationDay 2 at 3600 m

Sex-related differences between acetazolamide plasma concentration assessed by dried blood spots.

Hypoxic ventilatory responseDay 2 at 760 m

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.

Perceived pain visualizationDay 1 to 3 at 3600 m

Sex-related differences between acetazolamide and placebo group on perceived pain sensations, visualized by the SMaRT tablet app

Trial Locations

Locations (1)

National Center for Cardiology and Internal Medicine

🇰🇬

Bishkek, Kyrgyzstan

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