Clinical trial NCT05300477: Pharmacological Countermeasures for High Altitude
Official title: Augmentation of Medical Readiness and Physical Performance at High Altitude Using Pharmacological Countermeasures
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Hypobaric Hypoxia
Lead sponsor: United States Army Research Institute of Environmental Medicine
Sponsor class: FED
Collaborators: name: University of Puget Sound
First posted: 2022-03-29
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study will use a double-blind randomized study design in which one group will receive erythropoietin and the other group will receive the placebo for 4 weeks. After the 4 weeks, both groups will receive acetazolamide.
Primary purpose: OTHER

Brief summary: 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.

Detailed description: This study will use a double-blind randomized study design in which one group will receive erythropoietin and the other a placebo (saline) for 4 weeks, then both groups will receive acetazolamide. Eighteen men and women volunteers will complete 5 study phases: Phase 1) two week sea level baseline testing (orientation, two VO2peak assessments, three 3.2 km treadmill time-trial, assessment of resting ventilation, venipuncture and capillary blood collection, and Hbmass assessment), and a VO2peak and 3.2 km treadmill time-trial moderate altitude (3,000 m); Phase 2) 4 week intervention to receive subcutaneously erythropoietin or placebo. The erythropoietin (Procrit) dosing regimen will consist of 50 IU/kg three times a week (M-W-F); Phase 3) a second moderate altitude exposure (VO2peak and 3.2 km treadmill time-trial with acetazolamide administered (orally; 250 mg b.i.d) for 3 1/2 nights starting the day before the altitude exposure; Phase 4) high altitude acclimatization in which volunteers will reside for 15 days at 4,300 m altitude (Pikes Peak, Colorado Springs) completing multiple VO2peak assessments and 3.2 km treadmill time-trials, resting ventilation, venipuncture and capillary blood collection; and Phase 5) deacclimatization phase to assess changes in hematological biomarkers after returning from Pikes Peak. This study consists of 41 visits over a \~10 week time period. Visits will take place in Natick, MA and the Pikes Peak High Altitude Research Laboratory at Colorado Springs. Additional assessments that will be completed multiple times during the study include: acute mountain sickness questionnaire, lung gas diffusion at rest and during exercise, oxygen saturation, arterialized blood gases (PO2, PCO2, pH, HCO3) and heart rate during rest, exercise, and sleep, and muscle tissue oxygenation. The primary outcome is 3.2 km treadmill time-trial performance. Secondary outcomes include: incidence and severity of acute mountain sickness, ventilation and gas exchange, Hbmass, Hb concentration, Hct, arterialized blood gases, lung diffusion at rest and during exercise, oxygen saturation and heart rate during rest, exercise, and sleep.

Eligibility criteria: Inclusion Criteria:

* Age 18-40 years
* In good health as determined by the Office of Medical Support \& Oversight (OMSO) General Medical Clearance
* 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)
* 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
* Abstain from alcoholic beverages during the 15 day residence at the summit of Pikes Peak
* Abstain from drinking alcohol or caffeine at least 24 hours before a testing session during Phases 1 and 3
* Willing to stay and exercise in an altitude chamber (the size of a dorm room) for \~2.5 hours
* Wiling to reside at the summit of Pikes Peak (4,300 m altitude) and share dormitory area (bunk area, shower, and bathroom), potentially with people of the opposite sex for 15 days
* Up to date on COVID-19 vaccination

Exclusion Criteria:

* Women who are pregnant or planning to become pregnant during the study
* Taking prescription medication, or over-the-counter medications other than contraceptives, unless approved by OMSO \& PI
* Born at altitudes greater than 2,100 m (7,000 ft)
* Living in areas that are more than 1,200 m (4,000 ft) or have traveled to areas that are more than 1,200 m for five days or more within the last 2 months
* Prior diagnosis of High Altitude Pulmonary Edema (HAPE) or High Altitude Cerebral Edema (HACE)
* Musculoskeletal injuries that compromise the ability to walk/run on a treadmill or hike steep terrain
* Abnormal blood count in accordance with OMSO - Normal Hb men: 12.6-17.7 g·dL-1 and women: 11.1-15.9 g·dL-1 or Normal Hct men: 37.5-48% and women: 34.0-45%, or presence of abnormal blood chemicals (hemoglobin S or Sickle Cell Trait)
* Any history of malignancy
* Personal or family history of blood clots
* Abnormal prothrombin time/partial thromboplastin time (PT/PTT) test or problems with blood clotting
* History of thromboembolic disease, hypertension, and known risk factors of cardiovascular disease
* Blood donation within 8 weeks of beginning the study
* History of seizures
* History of inflammatory bowel disease
* Any recent (within 4-6 weeks) and or expected history of prolonged periods of immobility or limited activity (including recent or upcoming surgery)
* No evidence of iron deficiency (ferritin \< 45 ng/ml)
* Smokers or tobacco/nicotine (unless quit \> 1 month prior to study orientation)
* History of asthma
* Experience recent (\< 1 month of starting the study) cold, coughs, or respiratory tract infections
* Allergy to skin adhesive
* Known allergy to sulfa drugs
* Evidence of apnea or sleeping disorder
* Present condition of alcoholism, use of anabolic steroids, other substance abuse issues
* Inability to tolerate iron supplement

Primary outcomes:
measure: 3.2 km self-paced treadmill time trial performance
timeFrame: 35 minutes
Secondary outcomes:
measure: VO2peak
timeFrame: 30 minutes
measure: Lake Louise Acute Mountain Sickness Score
timeFrame: 10 minutes
measure: Ventilation rate
timeFrame: 20 minutes
measure: Percent body fat
timeFrame: 10 minutes
measure: Oxygen Saturation
timeFrame: 35 minutes
measure: Erythropoietin
timeFrame: 4 hours
measure: Hematocrit
timeFrame: 5 minutes
measure: Reticulocyte
timeFrame: 2 hours
measure: Ferritin
timeFrame: 2 hours
measure: C-reactive protein
timeFrame: 2 hours
measure: Soluble transferrin
timeFrame: 2 hours
measure: Arterialized capillary PO2
timeFrame: 5 minutes
measure: Arterialized capillary PCO2
timeFrame: 5 minutes
measure: Arterialized capillary pH
timeFrame: 5 minutes
measure: Hbmass
timeFrame: 20 minutes
measure: Muscle tissue oxygenation
timeFrame: 35 minutes
measure: Lung Diffusion of carbon monoxide
timeFrame: 35 minutes
Other outcomes:
Locations:
city: Natick
country: United States
facility: USARIEM
state: Massachusetts
Study officials:
affiliation: United States Army Research Institute of Environmental Medicine
name: Roy Salgado, PhD
role: PRINCIPAL_INVESTIGATOR
References: