HypoxemiaEarly Phase 1NCT07517068
The Role of Acetazolamide in Mitigating Inflammation and Innate Immune Activation at High Altitude
A Early Phase 1 study testing ACETAZOLAMIDE oral capsule in people with Hypoxemia and Acute Mountain Sickness (AMS), run by University of California, Riverside at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Hypoxemia, Acute Mountain Sickness (AMS), Inflammation
- What is being tested?
- ACETAZOLAMIDE oral capsule
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Sep 2025to 15 Dec 2026
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
This study will include men and women who meet the following inclusion criteria:
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, Riverside
Riverside, California, 92521
About this study
Official title: The Role of Acetazolamide in Mitigating Inflammation and Innate Immune Activation at High Altitude: a Randomized Cross-over Controlled Trial
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.
Read the detailed description
The primary research goal is to investigate the mechanisms underlying the pro-inflammatory response we observe at high altitude. The investigators believe that hypoxemia is a primary driver of this inflammatory response. High altitude exposure causes both chronic sustained hypoxemia due to reduced atmospheric oxygen availability, as well as concomitant nocturnal intermittent hypoxia on top of reduced baseline arterial oxygen pressures. Each of these hypoxic stressors may be drivers of pro-inflammatory responses. To determine if this is the case, ACZ will be used to improve oxygenation (SpO2) and ameliorate sleep disordered breathing at high altitude, thereby reducing the impacts of these factors on the immune response to high altitude.
As a secondary outcome, the study will determine if the anti-inflammatory properties of ACZ may play a key role in modulating AMS symptoms independent of ventilatory stimulation. This may reveal novel mechanisms of action of ACZ, but it is not the primary goal of this study.
The investigators hypothesize that (1) hypoxemia (both daytime chronic sustained hypoxia and noctournal intermittent hypoxia) is an independent driver of innate immune activation and pro-inflammatory responses at high altitude, and that (2) ACZ improves AMS symptoms, in part, by reducing systemic hypoxia-induced inflammation and reducing the activation of innate immune cells (monocytes and neutrophils). This hypothesis will be tested with the following experimental aims: (Aim 1) Determine if ACZ treatment during high altitude exposure blunts plasma inflammatory cytokine expression and levels of circulating pro-inflammatory innate immune cell subsets; (Aim 2) Determine if ACZ treatment during high altitude exposure modulates immune cell function (innate inflammatory responses to bacterial and viral stimuli, cell migration, and bacterial killing efficacy).
To test these hypotheses, this study utilizes a placebo controlled double-blind study design. Participants are prospectively assigned to either placebo or Acetazolamide treatment groups. Acetazolamide is prescribed at 125 mg per dose, taken twice per day starting 2 days before ascent and continuing for 3 days at high altitude.
Prior to ascent, participants complete baseline testing at low altitude. Testing includes collection of basic physiological parameters including height, weight, blood pressure, ECG, lung function testing by spirometry, and collection of self-reported medical history.
To determine the impact of treatment and altitude on breathing, ventilatory chemoreflex testing will be conducted at baseline , prior to starting treatment administration, as well as on day 2 at high altitude. Testing will be performed using a modified rebreathing method as described by Duffin (2007). From these tests, baseline tidal volume, frequency, and minute ventilation, the ventilatory recruitment threshold, and the hypoxic and hypercapnic ventilatory responses will be quantified and compared.
To determine the impact of treatment and altitude on immune parameters, peripheral venous blood samples will be collected during fasting at baseline, each morning at high altitude, and after 7 and 30 days after return to baseline elevation. From blood samples, plasma will be used to quantify expression of circulating inflammatory biomarkers, peripheral immune cells will be collected for flow cytometry analysis of immune cell population distributions as well as functional culture assays.
Additional measures of acute mountain sickness will be measured at baseline and twice per day (morning and evening) at high altitude, as well as 7 and 30 days following return to baseline using the Lake Louise AMS questionnaire and the Environmental Symptoms Questionnaire. Sleep quality will be assessed with the Stanford Sleepiness Scale.
- Being tested
- ACETAZOLAMIDE oral capsule, Placebo Arm
- Keywords
- Acetazolamide, Diamox, Hypoxia, High Altitude, Acute Mountain Sickness, AMS, Immune, Inflammation, SpO2
- Medical subject headings
- Hypoxia, Altitude Sickness, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ACETAZOLAMIDE oral capsuleDrug
Also called Acetazolamide
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.
Placebo ArmDevice
Not utilization of Acetazolamide (ACZ) oxygenation (SpO2) or any other supportive measurement will be used with this group.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Device: Placebo Arm |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: From enrollment to 2 years after completion of sample collection.
Secondary outcomes (5)
Expression of inflammatory biomarkers in peripheral blood
Expression of cytokines and markers of vascular inflammation will be measured via ELISA or multiplex assays. Measures will be collected at each timepoint (sea level, 1-3 days at high altitude, and 7 or 30 days following return to baseline).
Measured: From enrollment to 2 years after completion of sample collection.
Acute Mountain Sickness
Acute Mountain Sickness scores and other symptoms will be evaluated at each timepoint via the 2018 Lake Louise Acute Mountain Sickness scale. The Lake Louise Acute Mountain Sickness score for an individual is the sum of the score for the four symptoms (headache, nausea/vomiting, fatigue, and dizziness/light-headedness, each scored on a 0-3 scale with 3 being the most severe). For a positive AMS definition, it is mandatory to have a headache score of at least one point, and a total score of at least three points.
Measured: From enrollment to 2 years following sample collection.
Hypoxic ventilatory response
Hypoxic ventilatory responses will be measured at baseline before start of treatment administration, as well as after 2 days at high altitude. Measures will be evaluated using the Duffin modified rebreathing technique (Duffin 2007).
Measured: From enrollment to 2 years after data collection.
Hypercapnic ventilatory response
Hypercapnic ventilatory responses will be measured at baseline before start of treatment administration, as well as after 2 days at high altitude. Measures will be evaluated using the Duffin modified rebreathing technique (Duffin 2007).
Measured: From enrollment to 2 years after data collection
Minute ventilation at rest
Minute ventilation (L/min) at rest will be calculated as the product of tidal volume (L) and frequency (breaths per minute).
Measured: From enrollment to 2 years after data collection
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2026
- Study start17 Sep 2025
- Primary completion15 Jun 2026 (estimated)
- Study completion15 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HypoxemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Riverside
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Erica Heinrich, PhD, University of California, Riverside
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07517068
- Sponsor's protocol ID
- 30687
- Status last verified
- Apr 2026
- First submitted
- 29 Jan 2026
- Last updated
- 8 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant-level data will not be shared. Summary results will be provided to the sponsoring company and may be published in peer-reviewed journals.
Study at a glance
From the registry record, last updated by the sponsor on 8 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Acetazolamide in Mitigating Inflammation and Innate Immune Activation at High Altitude: a Randomized Cross-over Controlled Trial
- ClinicalTrials.gov ID
- NCT07517068
- Acronym / sponsor ID
- 30687
- Keywords
- Acetazolamide, Diamox, Hypoxia, High Altitude, Acute Mountain Sickness, AMS, Immune, Inflammation
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 19 participants (actual)
- Lead sponsor
- University of California, RiversideUniversity, hospital or other
- Study start
- 17 Sep 2025 (actual)
- Primary completion
- 15 Jun 2026 (estimated)
- Study completion
- 15 Dec 2026 (estimated)
- First posted
- 8 Apr 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The primary research goal is to investigate the mechanisms underlying the pro-inflammatory response we observe at high altitude. The investigators believe that hypoxemia is a primary driver of this inflammatory response. High altitude exposure causes both chronic sustained hypoxemia due to reduced atmospheric oxygen availability, as well as concomitant nocturnal intermittent hypoxia on top of reduced baseline arterial oxygen pressures. Each of these hypoxic stressors may be drivers of pro-inflammatory responses. To determine if this is the case, ACZ will be used to improve oxygenation (SpO2) and ameliorate sleep disordered breathing at high altitude, thereby reducing the impacts of these factors on the immune response to high altitude.
As a secondary outcome, the study will determine if the anti-inflammatory properties of ACZ may play a key role in modulating AMS symptoms independent of ventilatory stimulation. This may reveal novel mechanisms of action of ACZ, but it is not the primary goal of this study.
The investigators hypothesize that (1) hypoxemia (both daytime chronic sustained hypoxia and noctournal intermittent hypoxia) is an independent driver of innate immune activation and pro-inflammatory responses at high altitude, and that (2) ACZ improves AMS symptoms, in part, by reducing systemic hypoxia-induced inflammation and reducing the activation of innate immune cells (monocytes and neutrophils). This hypothesis will be tested with the following experimental aims: (Aim 1) Determine if ACZ treatment during high altitude exposure blunts plasma inflammatory cytokine expression and levels of circulating pro-inflammatory innate immune cell subsets; (Aim 2) Determine if ACZ treatment during high altitude exposure modulates immune cell function (innate inflammatory responses to bacterial and viral stimuli, cell migration, and bacterial killing efficacy).
To test these hypotheses, this study utilizes a placebo controlled double-blind study design. Participants are prospectively assigned to either placebo or Acetazolamide treatment groups. Acetazolamide is prescribed at 125 mg per dose, taken twice per day starting 2 days before ascent and continuing for 3 days at high altitude.
Prior to ascent, participants complete baseline testing at low altitude. Testing includes collection of basic physiological parameters including height, weight, blood pressure, ECG, lung function testing by spirometry, and collection of self-reported medical history.
To determine the impact of treatment and altitude on breathing, ventilatory chemoreflex testing will be conducted at baseline , prior to starting treatment administration, as well as on day 2 at high altitude. Testing will be performed using a modified rebreathing method as described by Duffin (2007). From these tests, baseline tidal volume, frequency, and minute ventilation, the ventilatory recruitment threshold, and the hypoxic and hypercapnic ventilatory responses will be quantified and compared.
To determine the impact of treatment and altitude on immune parameters, peripheral venous blood samples will be collected during fasting at baseline, each morning at high altitude, and after 7 and 30 days after return to baseline elevation. From blood samples, plasma will be used to quantify expression of circulating inflammatory biomarkers, peripheral immune cells will be collected for flow cytometry analysis of immune cell population distributions as well as functional culture assays.
Additional measures of acute mountain sickness will be measured at baseline and twice per day (morning and evening) at high altitude, as well as 7 and 30 days following return to baseline using the Lake Louise AMS questionnaire and the Environmental Symptoms Questionnaire. Sleep quality will be assessed with the Stanford Sleepiness Scale.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Acetazolamide treatment | Active comparator | Drug: ACETAZOLAMIDE oral capsuleAcetazolamide 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. |
| Placebo Treatment | Placebo comparator | Device: Placebo ArmThis 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ACETAZOLAMIDE oral capsuleAlso: AcetazolamideAcetazolamide 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 treatment |
| Placebo ArmNot utilization of Acetazolamide (ACZ) oxygenation (SpO2) or any other supportive measurement will be used with this group. | Device | Placebo Treatment |
Primary outcome
Distributions of circulating immune cell subsets.
Time frame: From enrollment to 30 days following return from high altitude (approximately 1.5 months total).
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.
Functional characteristics of peripheral immune cells.
Time frame: From enrollment to 2 years after completion of sample collection.
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.
5 secondary outcomes
Expression of inflammatory biomarkers in peripheral blood
Time frame: From enrollment to 2 years after completion of sample collection.
Acute Mountain Sickness
Time frame: From enrollment to 2 years following sample collection.
Hypoxic ventilatory response
Time frame: From enrollment to 2 years after data collection.
Hypercapnic ventilatory response
Time frame: From enrollment to 2 years after data collection
Minute ventilation at rest
Time frame: From enrollment to 2 years after data collection
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Apr 2026.
- Individual participant dataSharing planned: No. Individual participant-level data will not be shared. Summary results will be provided to the sponsoring company and may be published in peer-reviewed journals.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing ACETAZOLAMIDE oral capsule in people with Hypoxemia and Acute Mountain Sickness (AMS), run by University of California, Riverside at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 8 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Distributions of circulating immune cell subsets. (time frame: From enrollment to 30 days following return from high altitude (approximately 1.5 months total).). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Apr 2026; AzTrials last refreshed its copy on 26 Oct 2026.