Acetazolamide + Erythropoietin for Altitude Sickness

Recruiting in Natick (>99 mi)

Overseen By Roy M Salgado, Ph.D.

Age: 18 - 65

Sex: Any

Trial Phase: Phase 4

Sponsor: United States Army Research Institute of Environmental Medicine

Must not be taking: Prescription medications

Disqualifiers: Pregnancy, High altitude edema, Hypertension, Blood clots, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

18 Participants Needed

Trial Summary

What is the purpose of this trial?

The aim of this randomized, double-blind study is to determine whether erythropoietin (Procrit) and acetazolamide: 1) mitigates altitude-induced decrements in performance at moderate altitude (3,000 m) and 2) mitigates altitude-induced decrements in performance and reduce acute mountain sickness during prolonged exposure to high altitude (4,300 m; 15 days). Volunteers will complete 5 study phases: Phase 1) sea level baseline testing and a moderate altitude exposure; Phase 2) 4 week study intervention - randomly assigned to receive erythropoietin or placebo); Phase 3) 3 1/2 days of acetazolamide and a moderate altitude exposure; Phase 4) high altitude acclimatization - 15 days at Pikes Peak; and Phase 5) two week deacclimatization. Test battery include VO2peak, 3.2 km treadmill time trial, measures of gas exchange and ventilation during rest and exercise, and blood collection.

Will I have to stop taking my current medications?

The trial requires that you stop taking any prescription or over-the-counter medications, except contraceptives, unless approved by the study's medical team.

What data supports the effectiveness of the drug Acetazolamide for altitude sickness?

Research shows that Acetazolamide helps reduce symptoms of altitude sickness, such as headache, nausea, and weakness, by increasing oxygen levels in the blood. Studies with climbers have confirmed that those taking Acetazolamide reached higher altitudes with fewer symptoms compared to those taking a placebo. ^{1 2 3 4 5}

Is the combination of Acetazolamide and Erythropoietin generally safe for humans?

Acetazolamide is generally safe for preventing altitude sickness, but it can cause side effects like blurred vision and, in rare cases, serious issues like hemorrhagic gastritis, especially in people with kidney problems. It's important to use it carefully, especially if you have existing health conditions. ^{1 2 3 6 7}

How does the drug Acetazolamide + Erythropoietin for altitude sickness differ from other treatments?

This drug combination is unique because it combines acetazolamide, which helps prevent altitude sickness by reducing fluid buildup in the body, with erythropoietin, a hormone that stimulates red blood cell production, potentially enhancing oxygen delivery at high altitudes. This dual approach may offer a more comprehensive solution compared to treatments that only address one aspect of altitude sickness. ^{8 9 10 11 12}

Research Team

Roy Salgado, PhD

Principal Investigator

United States Army Research Institute of Environmental Medicine

Eligibility Criteria

This trial is for healthy adults aged 18-40 who are up to date with COVID-19 vaccinations, run regularly, and can complete a two-mile run within a specific time. Participants must avoid exercise, alcohol, and caffeine before testing sessions and be willing to live at high altitude for 15 days.

Inclusion Criteria

Willing to not exercise, or drink alcoholic and/or caffeinated beverages 24 hours prior to each testing session or the acute altitude exposure to 3,000 m

Up to date on COVID-19 vaccination

Runs at least 3 times per week and able to complete a two mile run in ≤ 21 minutes (Civilian Volunteers) or passed his/her most recent Army Combat Fitness Test (ACFT) (Military Volunteers Only)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

Multiple visits for baseline testing

Sea Level Baseline Testing

Orientation, VO2peak assessments, treadmill time-trials, resting ventilation, venipuncture, capillary blood collection, and Hbmass assessment

2 weeks

Multiple visits (in-person)

Moderate Altitude Exposure

VO2peak and treadmill time-trial at 3,000 m

3 1/2 days

In-person at moderate altitude

Intervention

Participants receive erythropoietin or placebo for 4 weeks

4 weeks

3 visits per week (in-person)

High Altitude Acclimatization

Participants reside at 4,300 m for 15 days with multiple assessments

15 days

In-person at high altitude

Deacclimatization

Assessment of changes in hematological biomarkers after returning from high altitude

2 weeks

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Acetazolamide
• Erythropoietin

Trial Overview The study tests if erythropoietin (Procrit) and acetazolamide help maintain physical performance and reduce sickness when exposed to moderate (3,000 m) and high altitudes (4,300 m). It's randomized and double-blind with five phases including baseline testing, medication/placebo intake, exposure to different altitudes, acclimatization period at Pikes Peak summit for 15 days followed by deacclimatization.

Participant Groups

Group I: Erythropoietin and Acetazolamide Experimental Treatment 2 Interventions

Erythropoietin (subcutaneously) 50 IU /kg three times a week for 4 weeks. After the 4 week Erythropoietin, acetazolamide (orally) 250 mg twice a day for 3 1/2 days.

Group II: Acetazolamide Experimental Treatment 1 Intervention

Acetazolamide (orally) 250 mg twice a day for 3 1/2 days.

Who Is Running the Clinical Trial?

United States Army Research Institute of Environmental Medicine

Lead Sponsor

Trials

67

Recruited

3,700+

University of Puget Sound

Collaborator

Trials

5

Recruited

210+

Findings from Research

Acetazolamide is effective in preventing acute mountain sickness, significantly reducing symptoms like headache and nausea, and its benefits are linked to increased arterial oxygen levels and reduced fluid retention.

While Acetazolamide can help treat established acute mountain sickness by improving oxygen levels, there is limited data on its effectiveness compared to other treatments like steroids or calcium channel blockers, and faster alternatives like Methazolamide may be more suitable in emergencies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acetazolamide and high altitude diseases. Bradwell, AR., Wright, AD., Winterborn, M., et al.[2013]

References

1. Germany pubmed.ncbi.nlm.nih.gov

[Prevention of altitude sickness]. [2016]

2. Germany pubmed.ncbi.nlm.nih.gov

Acetazolamide and high altitude diseases. [2013]

3. England pubmed.ncbi.nlm.nih.gov

Bilateral choroidal effusions after taking acetazolamide for altitude sickness. [2022]

4. France pubmed.ncbi.nlm.nih.gov

Acetazolamide and prevention of acute mountain sickness. [2015]

5. England pubmed.ncbi.nlm.nih.gov

Acetazolamide in prevention of acute mountain sickness: a double-blind controlled cross-over study. [2022]

6. Germany pubmed.ncbi.nlm.nih.gov

Acute hemorrhagic gastritis associated with acetazolamide intoxication in a patient with chronic renal failure. [2013]

7. England pubmed.ncbi.nlm.nih.gov

Effects of acetazolamide on overnight oxygenation and acute mountain sickness in patients with asthma. [2016]

8. United States pubmed.ncbi.nlm.nih.gov

A peptide-based erythropoietin-receptor agonist for pure red-cell aplasia. [2016]

9. United States pubmed.ncbi.nlm.nih.gov

Nonclinical Characterization of the Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor Roxadustat, a Novel Treatment of Anemia of Chronic Kidney Disease. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Transfusion Management of Incident Dialysis Patients in Canada: A Prospective Observational Study. [2022]

11. Switzerland pubmed.ncbi.nlm.nih.gov

New erythropoiesis-stimulating agents and new iron formulations. [2019]

12. England pubmed.ncbi.nlm.nih.gov

Erythropoiesis-stimulating agents for anaemia in adults with chronic kidney disease: a network meta-analysis. [2023]