Clinical trial NCT06499727: HighCycle Study: Effect of Acetazolamide on Acute Mountain Sickness in Women Compared to Men
Official title: HighCycle Study: Effect of Acetazolamide on Acute Mountain Sickness in Women Compared to Men: A Randomized, Placebo-Controlled, Double-Blind Parallel Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Acute Mountain Sickness
Keywords: Women
Hypoxia
Prevention
Acetazolamide
Altitude
Lead sponsor: University of Zurich
Sponsor class: OTHER
Collaborators: name: National Center of Cardiology and Internal Medicine named after academician M.Mirrakhimov
name: University Hospital Heidelberg
name: Laboratoire des Adaptations Métaboliques à l'Exercice en conditions Physiologiques et Pathologiques
First posted: 2024-07-12
Enrollment: 270
Sex: ALL
Minimum age (years): 18
Maximum age (years): 44
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: 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

Primary outcomes:
measure: Acute Mountain Sickness (AMS) Incidence, LLS 2018
timeFrame: Day 1 to 3 at 3600 m
Secondary outcomes:
measure: Acute Mountain Sickness (AMS) Incidence, LLS 1993
timeFrame: Day 1 to 3 at 3600 m
measure: Acute Mountain Sickness (AMS) Severity, LLS 2018
timeFrame: Day 1 to 3 at 3600 m
measure: Acute Mountain Sickness (AMS) Severity, LLS 1993
timeFrame: Day 1 to 3 at 3600 m
measure: Drug-related side effects
timeFrame: Day 1 to 3 at 3600 m
measure: Arterial blood gases
timeFrame: Day 2 at 760 m and day 2 at 3600 m
measure: Acetazolamide plasma concentration
timeFrame: Day 2 at 3600 m
measure: Hypoxic ventilatory response
timeFrame: Day 2 at 760 m
measure: Perceived pain visualization
timeFrame: Day 1 to 3 at 3600 m
Other outcomes:
Locations:
city: Bishkek
country: Kyrgyzstan
facility: National Center for Cardiology and Internal Medicine
Study officials:
affiliation: University of Zurich
name: Michael Furian, Prof. Dr.
role: STUDY_CHAIR
affiliation: National Center of Cardiology and Internal Medicine, Bishkek, Kyrgyzstan
name: Talant Sooronbaev, Prof. Dr.
role: STUDY_DIRECTOR
References: