The Role of Acetazolamide in Mitigating Inflammation and Innate Immune Activation at High Altitude

NCT07517068 | Active Not Recruiting Early Phase 1 FDA Drug

• 1 other identifier: 30687
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

High altitude travel can lead to inflammation in the body and activation of innate immune cells. The investigators' prior research demonstrates that 1 to 3 days at 3800 m elevation leads to increased expression of genes in blood cells that code for proteins that signal cell damage (damage associated molecular patterns (DAMPs)), cell receptors involved in innate immune responses, as well as increases in monocyte and neutrophil cells which promote inflammation. This study will investigate the potential mechanisms underlying these effects using the drug Acetazolamide, a carbonic anhydrase inhibitor which is known to reduce symptoms of Acute Mountain Sickness.

Conditions

Hypoxemia; Acute Mountain Sickness (AMS); Inflammation; Immune Response

Keywords

Acetazolamide; Diamox; Hypoxia; High Altitude; Acute Mountain Sickness; AMS; Immune; Inflammation; SpO2

Outcome Measures

Primary Outcomes (2)

• Distributions of circulating immune cell subsets.

  Distributions of peripheral leukocyte subsets in peripheral blood will be quantified at each timepoint of exposure (sea level before ascent, days 1-3 at high altitude, and days 7 and 30 following return to sea level) and in each treatment condition (placebo and ACZ). Blood samples will be collected in the morning immediately following waking, while fasting. Cell distributions will be determined via flow cytometry.

  From enrollment to 30 days following return from high altitude (approximately 1.5 months total).

• Functional characteristics of peripheral immune cells.

  Peripheral blood mononuclear cells (PBMCs) will be collected at each timepoint for each participant. Cells will be isolated and cryopreserved immediately following blood collection. Cells will then be transported to the laboratory at UC Riverside if collected in the field. To determine the inflammatory reactivity and sensitivity of PBMCs at each timepoint, we will culture these cells in the presence or absence of bacterial (lipopolysaccharide, LPS) and viral stimuli (R848) and measure the concentration of inflammatory cytokines (TNFa) produced by the cells as a result of this stimuli.

  From enrollment to 2 years after completion of sample collection.

Secondary Outcomes (5)

• Expression of inflammatory biomarkers in peripheral blood

  From enrollment to 2 years after completion of sample collection.

• Acute Mountain Sickness

  From enrollment to 2 years following sample collection.

• Hypoxic ventilatory response

  From enrollment to 2 years after data collection.

• Hypercapnic ventilatory response

  From enrollment to 2 years after data collection

• Minute ventilation at rest

  From enrollment to 2 years after data collection

Study Arms (2)

Acetazolamide treatment

ACTIVE COMPARATOR

Acetazolamide is administered orally in pill form at a 125 mg dose taken twice per day (morning and evening) starting 2 days before ascent to high altitude and each day while at high altitude.

Drug: ACETAZOLAMIDE oral capsule

Placebo Treatment

PLACEBO COMPARATOR

This group will not be provided ACZ. Instead, participants will take a placebo compound in pill form resembling ACZ on the same schedule as the ACZ treatment.

Device: Placebo Arm

Interventions

ACETAZOLAMIDE oral capsule DRUG

Acetazolamide is administered orally in pill form at a 125 mg dose taken twice per day (morning and evening) starting 2 days before ascent to high altitude and each day while at high altitude.

Also known as: Acetazolamide

Acetazolamide treatment

Placebo Arm DEVICE

Not utilization of Acetazolamide (ACZ) oxygenation (SpO2) or any other supportive measurement will be used with this group.

Placebo Treatment

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Between ages 18 and 65
• No history of cardiovascular or pulmonary disease (previously diagnosed or indicated by EKG, spirometry, and other medical history)
• No history of high altitude pulmonary or cerebral edema (HAPE or HACE)
• No history of obstructive or central sleep apnea
• No current use of anti-inflammatory medication, steroids, stimulants, or other agents that may interfere with ventilatory chemosensitivity
• No current pregnancy
• No travel above 8,000 feet elevation within 1 month of the first measures
• Non-smokers (including any type of vape use, marijuana usage)
• No current or recently treated systemic or serious local infection
• Must be fluent in the English language
• Participants must refrain from consuming alcohol for at least 1 week prior to the start of the study, throughout the duration of their participation, and for 2 days prior to their follow-up visits.
• Caffeine and other stimulants may not be consumed during the course of participation in the high-altitude portion of the study (including 12 hours before sea level baseline measures, then starting 2 days before ascent and ending upon return to sea level).
• Strenuous physical activity including hiking to higher elevations is not permitted during the high altitude portion of the study.

Sponsors & Collaborators

• University of California, Riverside: lead

Study Sites (1)

University of California, Riverside

Riverside, California, 92521, United States

Location

MeSH Terms

Conditions

Hypoxia; Altitude Sickness; Inflammation

Interventions

Acetazolamide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Individuals completing statistical analyses will be blinded to participant treatments. Treatment distributions are developed and maintained by a pharmacy team who prepare treatments for participants. Pharmacy team personnel provide a physician team member with the coded treatment orders for prescription and distribution to participants.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, Biomedical Science

Model Details: Participants are randomly assigned to receive Acetazolamide or Placebo treatments. Participants and study personnel are blinded to treatments. Treatment usage begins 2 days prior to ascent to high altitude and throughout three days of high altitude exposure.

Study Record Dates

• First Submitted: January 29, 2026
• First Posted: April 8, 2026
• Study Start: September 17, 2025
• Primary Completion: June 15, 2026
• Study Completion (Estimated): December 15, 2026
• Last Updated: April 8, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)