Pharmacological Countermeasures for High Altitude

Hypobaric Hypoxia Clinical Trial

Official title:

Augmentation of Medical Readiness and Physical Performance at High Altitude Using Pharmacological Countermeasures

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05300477
• Other study ID #: 21-06HC (M-10910)
• Status: Recruiting
• Phase: Phase 4
• Start date: May 27, 2022
• Est. completion date: August 30, 2022

Study information

• Verified date: March 2022
• Source: United States Army Research Institute of Environmental Medicine
• Contact: Roy M Salgado, Ph.D.
• Phone: 508-206-2375
• Email: roy.m.salgado.civ[@]mail.mil
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 18
• Est. completion date: August 30, 2022
• Est. primary completion date: August 30, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 40 Years

Eligibility

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

Related Conditions & MeSH terms

• Hypobaric Hypoxia
• Hypoxia

Intervention

Drug:
• Acetazolamide
Carbonic Anhydrase Inhibitor
• Erythropoietin
Hormone for red blood cell

Locations

Country	Name	City	State
United States	USARIEM	Natick	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
United States Army Research Institute of Environmental Medicine	University of Puget Sound

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	3.2 km self-paced treadmill time trial performance	Time to complete self-paced 3.2 km treadmill time trial (min:sec)	35 minutes
Secondary	VO2peak	Peak aerobic capacity will be assessed using a metabolic cart.	30 minutes
Secondary	Lake Louise Acute Mountain Sickness Score	Acute mountain sickness and severity will be assessed using the Lake Louise acute mountain sickness questionnaire. This Likert scale assess acute mountain sickness with scores ranging from 0 to 12. Zero indicates no acute mountain sickness and 12 indicates severe acute mountain sickness.	10 minutes
Secondary	Ventilation rate	Ventilation rate will be assessed using a pneumotachometer.	20 minutes
Secondary	Percent body fat	Percent body fat will be assessed using Dual Energy X-ray Absorptiometry.	10 minutes
Secondary	Oxygen Saturation	Oxygen saturation will be assessed using a finger pulse oximeter.	35 minutes
Secondary	Erythropoietin	Erythropoietin will be assessed using an ELISA.	4 hours
Secondary	Hematocrit	Hematocrit will be assessed using manual hematocrit method.	5 minutes
Secondary	Reticulocyte	Reticulocyte will be assessed using a hematology analyzer.	2 hours
Secondary	Ferritin	Ferritin will be assessed using an ELISA.	2 hours
Secondary	C-reactive protein	C-reactive protein will be assessed using an ELISA.	2 hours
Secondary	Soluble transferrin	Soluble transferrin will be assessed using an ELISA.	2 hours
Secondary	Arterialized capillary PO2	Arterialized capillary PO2 will be assessed using a blood gas analyzer.	5 minutes
Secondary	Arterialized capillary PCO2	Arterialized capillary PCO2 will be assessed using a blood gas analyzer.	5 minutes
Secondary	Arterialized capillary pH	Arterialized capillary pH will be assessed using a blood gas analyzer.	5 minutes
Secondary	Hbmass	Hbmass will be assessed using the CO-rebreathing procedure.	20 minutes
Secondary	Muscle tissue oxygenation	Muscle tissue oxygenation will be assessed using a non-invasive near-infrared spectroscopy.	35 minutes
Secondary	Lung Diffusion of carbon monoxide	Lung Diffusion of carbon monoxide will be assessed using a spirometer.	35 minutes