HighCycle Study: Acetazolamide, High Altitude and Plasma Volume

Centre d'Expertise sur l'Altitude EXALT

Status and phase: Enrolling; Phase 4

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

Treatments: Drug: Placebo; Drug: Acetazolamide

Study type: Interventional

Funder types: Other

Identifiers

NCT07118462

HighCycle_PV

Details and patient eligibility

About

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.

Full description

Not provided

Enrollment: 270 estimated patients

Sex: All

Ages: 18 to 44 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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270 participants in 2 patient groups, including a placebo group

Acetazolamide

Experimental group

Description:

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

Treatment:

Drug: Acetazolamide

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo