HighCycle Study: Acetazolamide, High Altitude and Plasma Volume

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.

Conditions

• High Altitude Effects
• High Altitude Hypoxia
• Acute Mountain Sickness (AMS)
• Plasma Volume
• Women

Interventions

DRUG

Acetazolamide

Administration of 1x125mg acetazolamide in the morning, 1x125mg in the evening, starting 24 hours before departure to 3600 m.

DRUG

Placebo

Administration of equally looking placebo capsules in the morning and in the evening, starting 24 hours before departure to 3600 m.

Sponsors & Collaborators

• National Center of Cardiology and Internal Medicine named after academician M.Mirrakhimov

  collaborator OTHER_GOV

• University of Zurich

  collaborator OTHER

• Centre d'Expertise sur l'Altitude EXALT

  lead OTHER

Principal Investigators

• Michael Furian, Prof. Dr. · University of Zurich

• Talant M Sooronbaev, Prof. Dr. · National Center of Cardiology and Internal Medicine, Bishkek, Kyrgyzstan

• Paul Robach, PhD · EXALT (Centre d'Expertise sur l'Altitude), Grenoble, France

• Benoit Champigneulle, MD, PhD · EXALT (Centre d'Expertise sur l'Altitude), Grenoble, France

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

44 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2024-07-15

Primary Completion

2025-12-31

Completion

2025-12-31

Countries

• Kyrgyzstan

Study Locations