HighCycle Study: Acetazolamide, High Altitude and Plasma Volume

Not Applicable

Recruiting

• Conditions: High Altitude Effects; High Altitude Hypoxia; Acute Mountain Sickness (AMS); Plasma Volume; Women
• Interventions: Drug: Acetazolamide; 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

Study Timeline

• Study Start: 2024-07-15
• Status Verified: 2025-08
• Study First Submitted: 2025-08-05
• Study First Submitted QC: 2025-08-11
• Last Update Submitted: 2025-08-11
• Study First Posted: 2025-08-12
• Last Update Posted: 2025-08-12
• Primary Completion: 2025-12-31
• Study Completion: 2025-12-31

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

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