Acute Mountain Sickness
Conditions
Keywords
Women, Hypoxia, Prevention, Acetazolamide, Altitude
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.
Interventions
DRUGAcetazolamide
Administration of 1x125mg acetazolamide in the morning, 1x125mg in the evening, starting 24 hours before departure to 3600 m.
DRUGPlacebo
Administration of equally looking placebo capsules in the morning and in the evening, starting 24 hours before departure to 3600 m.
Sponsors
University of Zurich
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
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 44 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Acute Mountain Sickness (AMS) Incidence, LLS 2018 | Day 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
| Measure | Time frame | Description |
|---|---|---|
| Acute Mountain Sickness (AMS) Incidence, LLS 1993 | Day 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 2018 | Day 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 1993 | Day 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 effects | Day 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 gases | Day 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 concentration | Day 2 at 3600 m | Sex-related differences between acetazolamide plasma concentration assessed by dried blood spots. |
| Hypoxic ventilatory response | Day 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 visualization | Day 1 to 3 at 3600 m | Sex-related differences between acetazolamide and placebo group on perceived pain sensations, visualized by the SMaRT tablet app |
Countries
Kyrgyzstan
Contacts
STUDY_CHAIRMichael Furian, Prof. Dr.
University of Zurich
STUDY_DIRECTORTalant Sooronbaev, Prof. Dr.
National Center of Cardiology and Internal Medicine, Bishkek, Kyrgyzstan
Outcome results
None listed