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

NCT06499727 | Completed Phase 4

• 1 other identifier: HighCycle_AMS
• Study Type: interventional
• Target: 303
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Mountain Sickness

Keywords

Women; Hypoxia; Prevention; Acetazolamide; Altitude

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Acute Mountain Sickness (AMS) Incidence, LLS 1993

  Day 1 to 3 at 3600 m

• Acute Mountain Sickness (AMS) Severity, LLS 2018

  Day 1 to 3 at 3600 m

• Acute Mountain Sickness (AMS) Severity, LLS 1993

  Day 1 to 3 at 3600 m

• Drug-related side effects

  Day 1 to 3 at 3600 m

• Arterial blood gases

  Day 2 at 760 m and day 2 at 3600 m

Study Arms (4)

WOMEN - ACETAZOLAMIDE oral capsule

ACTIVE COMPARATOR

Acetazolamide 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.

Drug: Acetazolamide

MEN - ACETAZOLAMIDE oral capsule

ACTIVE COMPARATOR

Acetazolamide 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.

Drug: Acetazolamide

WOMEN - PLACEBO oral capsule

PLACEBO COMPARATOR

Placebo (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.

Drug: Placebo

MEN - PLACEBO oral capsule

PLACEBO COMPARATOR

Placebo (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.

Drug: Placebo

Interventions

Placebo DRUG

Administration of equally looking placebo capsules in the morning and in the evening, starting 24 hours before departure to 3600 m.

MEN - PLACEBO oral capsule; WOMEN - PLACEBO oral capsule

Acetazolamide DRUG

Administration of 1x125mg acetazolamide in the morning, 1x125mg in the evening, starting 24 hours before departure to 3600 m.

MEN - ACETAZOLAMIDE oral capsule; WOMEN - ACETAZOLAMIDE oral capsule

Eligibility Criteria

• Age: 18 Years - 44 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Zurich: lead
• University Hospital Heidelberg: collaborator
• National Center of Cardiology and Internal Medicine named after academician M.Mirrakhimov: collaborator
• Laboratoire des Adaptations Métaboliques à l'Exercice en conditions Physiologiques et Pathologiques: collaborator

Study Sites (1)

National Center for Cardiology and Internal Medicine

Bishkek, Gorod Bishkek, 720040, Kyrgyzstan

Location

MeSH Terms

Conditions

Altitude Sickness; Hypoxia

Interventions

Acetazolamide

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiadiazoles; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Michael Furian, Prof. Dr.

  University of Zurich

  STUDY CHAIR

• Talant Sooronbaev, Prof. Dr.

  National Center of Cardiology and Internal Medicine, Bishkek, Kyrgyzstan

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 5, 2024
• First Posted: July 12, 2024
• Study Start: July 15, 2024
• Primary Completion: August 31, 2025
• Study Completion: August 31, 2025
• Last Updated: January 23, 2026

Record last verified: 2025-05

Locations

KY (1)