HighCycle Study: Acetazolamide, High Altitude and Plasma Volume

NCT07118462 | Recruiting Phase 4

• 1 other identifier: HighCycle_PV
• Study Type: interventional
• Target: 270
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

acetazolamide; plasma volume; acute mountain sickness; high altitude; hypoxia; women

Outcome Measures

Primary Outcomes (1)

• Plasma volume

  Change in plasma volume assessed by the CO-rebreathing method in acetazolamide versus placebo group

  Day 1 at 760 m then Day 2 and Day 3 at 3,600 m.

Secondary Outcomes (4)

• Plasma volume : sex-related difference

  Day 1 at 760 m then Day 2 and Day 3 at 3600 m.

• Plasma volume : AMS-related difference

  Day 1 at 760 m then Day 2 and Day 3 at 3600 m.

• Hormones

  Day 2 at 760 m and Day 2 at 3600 m.

• Arterial blood gases

  Day 2 at 760 m and Day 2 at 3600 m.

Study Arms (2)

Acetazolamide

EXPERIMENTAL

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

Drug: Acetazolamide

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Acetazolamide DRUG

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

Also known as: Diamox®

Acetazolamide

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years - 44 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Centre d'Expertise sur l'Altitude EXALT: lead
• National Center of Cardiology and Internal Medicine named after academician M.Mirrakhimov: collaborator
• University of Zurich: collaborator

Study Sites (1)

National Center for Cardiology and Internal Medicine

Bishkek, 720040, Kyrgyzstan

RECRUITING

MeSH Terms

Conditions

Altitude Sickness; Hypoxia

Interventions

Acetazolamide

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiadiazoles; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Michael Furian, Prof. Dr.

  University of Zurich

  STUDY CHAIR

• Talant M Sooronbaev, Prof. Dr.

  National Center of Cardiology and Internal Medicine, Bishkek, Kyrgyzstan

  STUDY DIRECTOR

• Paul Robach, PhD

  EXALT (Centre d'Expertise sur l'Altitude), Grenoble, France

  PRINCIPAL INVESTIGATOR

• Benoit Champigneulle, MD, PhD

  EXALT (Centre d'Expertise sur l'Altitude), Grenoble, France

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Benoit Champigneulle, MD PhD

CONTACT

+33476769288; BChampigneulle@chu-grenoble.fr

Paul Robach, PhD

CONTACT

+33667053919; paul.robach@ensm.sports.gouv.fr

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2025
• First Posted: August 12, 2025
• Study Start: July 15, 2024
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: August 12, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share

Locations

KY (1)