HighCycle Study: Acetazolamide, High Altitude and Plasma Volume
- Conditions
- High Altitude EffectsHigh Altitude HypoxiaAcute Mountain Sickness (AMS)Plasma VolumeWomen
- Interventions
- Drug: Placebo
- Registration Number
- NCT07118462
- Lead Sponsor
- Centre d'Expertise sur l'Altitude EXALT
- Brief Summary
Each year, millions of people living at low altitude (\< 1,000 m) travel to high altitude (≥ 2,500 m) for work, tourism, or sports activities. These individuals are exposed to hypobaric hypoxia, which can trigger acute mountain sickness (AMS)-the most common form of altitude-related illness. Therefore, understanding the physiological responses to hypoxia that allow acclimatization, as well as the pathophysiology of acute mountain sickness, is of primary importance.
The hematological response to high-altitude exposure initially includes a reduction in plasma volume (PV), leading to an early increase in hemoglobin concentration within the first 24 hours. In contrast, an increase in hemoglobin mass requires several weeks at high altitude. Recent well-controlled physiological studies conducted in hypobaric chambers have demonstrated that this hypoxia-induced PV contraction results from fluid redistribution from the intravascular to the extravascular compartment, rather than from water loss due to increased diuresis.
Prophylaxis of AMS is primarily based on the administration of 250 mg/day of acetazolamide (ACZ), a carbonic anhydrase inhibitor with a mild diuretic effect. Acetazolamide induces metabolic acidosis, which stimulates ventilation and thereby improves oxygenation. The effect of prophylactic ACZ use during high-altitude exposure on PV in lowlanders remains unknown: it is unclear whether ACZ leads to a greater reduction in PV due to its diuretic effect, or to a smaller hypoxia-induced PV contraction as a result of improved oxygenation induced by increased ventilation.
- Detailed Description
Not provided
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 270
- 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.
- 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
Group Intervention Description Acetazolamide Acetazolamide 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 Placebo Placebo 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.
- Primary Outcome Measures
Name Time Method Plasma volume Day 1 at 760 m then Day 2 and Day 3 at 3,600 m. Change in plasma volume assessed by the CO-rebreathing method in acetazolamide versus placebo group
- Secondary Outcome Measures
Name Time Method Plasma volume : sex-related difference Day 1 at 760 m then Day 2 and Day 3 at 3600 m. Sex-related differences in the effect of acetazolamide vs.placebo in plasma volume at high altitude.
Plasma volume : AMS-related difference Day 1 at 760 m then Day 2 and Day 3 at 3600 m. Difference in plasma volume change at high altitude between AMS+ and AMS- participants.
Hormones Day 2 at 760 m and Day 2 at 3600 m. Changes in copeptin and midregional proANP serum levels between acetazolamide and placebo group and sex-related difference
Arterial blood gases Day 2 at 760 m and Day 2 at 3600 m. Changes in the arterial blood gases (pH, PaO2, PaCO2, SaO2) between acetazolamide and placebo group.
Trial Locations
- Locations (1)
National Center for Cardiology and Internal Medicine
🇰🇬Bishkek, Kyrgyzstan
National Center for Cardiology and Internal Medicine🇰🇬Bishkek, KyrgyzstanTalant M Sooronbaev, Prof. Dr.Contact+996 312 625679sooronbaev@yahoo.com