Three New Ideas to Protect Special Forces From the Stress of High Altitude

Study Overview
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Brief Summary
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Acute Mountain Sickness (AMS) is a well-documented syndrome that affects 42% of non-acclimatized individuals traveling to altitudes above 10,000 feet. Decreased barometric pressure, which leads to low blood oxygen levels, is the primary casual factor of AMS. Symptoms of AMS are characterized by headache, nausea, vomiting, dizziness, fatigue and difficultly sleeping. Moreover, when people travel to high altitude, cognitive performance and endurance exercise capacity are impaired. Therefore, the goal of this research is to identify effective pharmacological agents that will help reduce the symptoms of AMS and improve physical and cognitive performance at high altitude. The investigators will study the efficacy of the dietary supplement, quercetin, the drugs nifedipine (extended release) and methazolamide taken together, the drug metformin, and the drug nitrite in reducing symptoms of AMS and improving cognitive and exercise performance at high altitudes.

Official Title
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Three New Ideas to Protect Special Forces From the Stress of High Altitude

Conditions
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Mountain Sickness

Intervention / Treatment
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* Dietary Supplement: Quercetin
* Drug: Nifedipine extended release
* Drug: Methazolamide
* Drug: Metformin
* Drug: Placebo
* Drug: Nitrite


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: healthy, young (18-30 years old) men who can meet APFT requirements for special operation forces (SOF) training as outlined by the US Army (42 push ups, 53 sit-ups, 6 pull-ups, 2 mile run in < 15 min 54 s) Exclusion Criteria: women; smokers; participants with diseases or disorders known to be affected by hypoxia or the drugs used in this study, such as hypotension, anemia, sickle cell trait or disease, and diabetes; participants with a history of significant head injury, migraines or seizures; participants taking any medication (over-the-counter or prescription) or herbal supplements; participants with known flavonoid allergies; participants with known allergies to metformin; participants with known hypersensitivity reaction to nifedipine; participants with known allergies to sulfonamide-based drugs; participants with inability to be headache-free when consuming the amount of caffeine in two six ounce cups of coffee or less per day; exposure to high altitude above 1000m in the previous three months; or participants who have been on an airline flight over six hours (the lowered cabin pressure for an extended period of time approximates exposure to high altitude); participants who are unable to achieve the minimum physical criteria required for SOF training

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Factorial Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Quercetin<br>Quercetin: 500mg pill, twice daily for 5 days | Dietary Supplement: Quercetin<br> <br> |
| Experimental: Nifedipine+Methazolamide<br>Nifedipine extended release: 30mg pill, twice daily for 5 days; Methazolamide: 125mg pill, twice daily for 5 days | Drug: Nifedipine extended release<br> <br> Drug: Methazolamide<br> <br> |
| Experimental: Metformin<br>Metformin: 500mg pill, once daily for 2 days, then 500mg twice daily at altitude (3 days) | Drug: Metformin<br> <br> |
| Placebo Comparator: Placebo<br>Sugar pill manufactured to look like all other investigational products | Drug: Placebo<br> <br> |
| Experimental: Nitrite<br>Nitrite: 20mg pill, three times daily for 5 days | Drug: Nitrite<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Environmental Symptoms Questionnaire at High Altitude | Self-reported assessment of AMS symptoms (headache, lightheaded, dizzy, etc.). The 11-item Environmental Symptoms Questionnaire measures Acute Mountain Sickness symptoms (nausea, weakness, lightheadedness, dizziness, headache, etc.). Possible scores range from 0 to 55 (0-5 per item), with higher scores indicating a better outcome. | Baseline and during high altitude exposure (3 days, AM/PM) | 
| Change in Lake Louise AMS Scoring System at High Altitude | Self-reported assessment of AMS symptoms (headache, nausea, vomiting, dizziness, fatigue and difficultly sleeping). The Lake Louise AMS Scoring System measures symptoms of altitude sickness. Possible scores range from 0 to 16, with higher scores indicating a worse outcome. | Baseline and during high altitude exposure (3 days, AM/PM) | 
| Change in Army Physical Fitness Test (APFT) at High Altitude | Timed 2 mile run, push-ups, sit-ups, and pull-ups. The Army Physical Fitness Test (APFT) measures physical fitness. Higher scores indicate a better outcome. A score of 60 is considered minimum passing score. The maximum possible score is 300, indicating the highest level of physical fitness. | Baseline, 1st day at high altitude | 
| Change in Uphill Hike at High Altitude | Timed 3.1 mile uphill run/hike, with weighted back-pack | 2nd day at altitude | 
| Change in Defense Automated Neurobehavioral Assessment (DANA) Reaction Time at High Altitude | Battery of nine cognitive function tests. The Defense Automated Neurobehavioral Assessment (DANA) measures cognitive function and was used to measure mean reaction time. Possible scores range from 180 to 500 milliseconds, with lower scores indicating a better outcome. | Baseline and and 1st day at high altitude | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Exercise, Aerobic, Cognitive Function