Acetazolamide + Erythropoietin for Altitude Sickness

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether erythropoietin and acetazolamide (a medication often used to prevent altitude sickness) can reduce altitude sickness and enhance physical performance at high altitudes. The research involves spending time at various altitudes, including a two-week stay on Pikes Peak, to evaluate the effectiveness of these treatments. It seeks healthy individuals who run regularly and can complete a two-mile run in 21 minutes or less. Participants must be willing to stay at high altitudes and adhere to specific exercise and diet restrictions during the trial. As a Phase 4 trial, this study involves treatments already FDA-approved and proven effective, aiming to understand how they can benefit more patients.

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 is the safety track record for these treatments?

Research has shown that acetazolamide is generally safe and effective for altitude sickness. It helps individuals acclimate to high altitudes and reduces symptoms such as headaches and dizziness. Most people do not experience serious side effects, though some may have mild issues like blurred vision.

The FDA has approved erythropoietin for treating anemia, indicating a known safety record. However, like any treatment, it can cause side effects. This study uses both acetazolamide and erythropoietin together to determine if they can prevent altitude sickness. As the trial is in a later phase, there is strong evidence of safety, but participants should be aware of the potential for mild side effects from both medications. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about combining acetazolamide and erythropoietin for altitude sickness because this approach could enhance the body's ability to adapt to high altitudes more effectively than current treatments. While acetazolamide is already used to prevent and reduce the symptoms of altitude sickness by helping balance the body's acid-base levels, adding erythropoietin introduces a new dimension by potentially boosting red blood cell production, which can improve oxygen delivery throughout the body. This dual approach targets both the respiratory and hematological challenges of high altitudes, potentially offering quicker and more comprehensive relief than the standard treatment of acetazolamide alone.

What evidence suggests that this trial's treatments could be effective for altitude sickness?

Research has shown that acetazolamide, one of the treatments in this trial, effectively prevents altitude sickness, also known as acute mountain sickness (AMS). It significantly reduces the risk of severe AMS compared to a placebo, with studies finding a relative risk of 0.70. Acetazolamide increases oxygen levels in the blood, easing symptoms like headache, nausea, and weakness. Another arm of this trial will investigate the combination of erythropoietin with acetazolamide, although acetazolamide alone already has a strong track record for preventing altitude sickness. ^{1 6 7 8 9}

Who Is on the Research Team?

Roy Salgado, PhD

Principal Investigator

United States Army Research Institute of Environmental Medicine

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8588948/

Efficacy of acetazolamide for the prophylaxis of acute ... Acetazolamide treatment showed to have significantly lower incidence of severe AMS compared with placebo (RR = 0.70, 95% CI, 0.52–0.95; P = 0.02; I2 = 3.6%).

2. journals.plos.org journals.plos.org/plosone/article?id=10.1371/journal.pone.0319689

The efficacy and safety of acetazolamide in chronic mountain ... Numerous studies have shown that ACZ is effective in preventing AMS in healthy lowlanders traveling to high-altitude regions [20,21], and it also prevents ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03828474

Sickness Evaluation at Altitude With Acetazolamide ... A randomized controlled trial confirmed effectiveness of acetazolamide 125mg twice daily in prevention of AMS when started prior to ascent. In this study, it ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0002934320304393

A Randomized Controlled Trial of the Lowest Effective ... Acetazolamide 62.5 mg twice daily failed to demonstrate equal effectiveness to 125 mg twice daily for prevention of acute mountain sickness.

5. liebertpub.com liebertpub.com/doi/full/10.1089/ham.2019.0123

Altitude, Acute Mountain Sickness, and Acetazolamide Doses 500–750 mg/day within 24 hours of altitude exposure appear to be the most effective for minimizing symptoms of AMS.

6. cdc.gov cdc.gov/yellow-book/hcp/environmental-hazards-risks/high-altitude-travel-and-altitude-illness.html

High-Altitude Travel and Altitude Illness | Yellow Book Consider using acetazolamide to speed acclimatization if abrupt ascent is unavoidable. Avoid alcohol for the first 48 hours at high altitude. If ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/819341/

[Prevention of altitude sickness] Persons taking Acetazolamide were more efficient and better prepared to cope with the extreme situations in high altitude. They also showed to be more resistent ...

8. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK430716/

Acute Mountain Sickness - StatPearls - NCBI Bookshelf - NIH Acetazolamide is the most commonly used pharmacologic agent for both prophylaxis and treatment of AMS. As a carbonic anhydrase inhibitor, ...

9. mayoclinic.org mayoclinic.org/drugs-supplements/acetazolamide-oral-route/description/drg-20535236

Acetazolamide (oral route) - Side effects & dosage Adults—500 to 1000 milligrams (mg) in divided doses, taken 24 to 48 hours before climbing, then continue for 48 hours while on high altitude or ...