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

Phase 4

Completed

Conditions: Mountain Sickness

Interventions: Dietary Supplement: Quercetin
Drug: Nifedipine extended release
Drug: Placebo
Drug: Metformin
Drug: Nitrite
Drug: Methazolamide

Registration Number: NCT02463357

Lead Sponsor: University of Colorado, Denver

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 148

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Quercetin	Quercetin	Quercetin: 500mg pill, twice daily for 5 days
Nifedipine+Methazolamide	Nifedipine extended release	Nifedipine extended release: 30mg pill, twice daily for 5 days; Methazolamide: 125mg pill, twice daily for 5 days
Placebo	Placebo	Sugar pill manufactured to look like all other investigational products
Nifedipine+Methazolamide	Methazolamide	Nifedipine extended release: 30mg pill, twice daily for 5 days; Methazolamide: 125mg pill, twice daily for 5 days
Metformin	Metformin	Metformin: 500mg pill, once daily for 2 days, then 500mg twice daily at altitude (3 days)
Nitrite	Nitrite	Nitrite: 20mg pill, three times daily for 5 days

Primary Outcome Measures

Name	Time	Method
Change in Environmental Symptoms Questionnaire at High Altitude	Baseline and during high altitude exposure (3 days, AM/PM)	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.
Change in Lake Louise AMS Scoring System at High Altitude	Baseline and during high altitude exposure (3 days, AM/PM)	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.
Change in Army Physical Fitness Test (APFT) at High Altitude	Baseline, 1st day 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.
Change in Uphill Hike at High Altitude	2nd day at altitude	Timed 3.1 mile uphill run/hike, with weighted back-pack
Change in Defense Automated Neurobehavioral Assessment (DANA) Reaction Time at High Altitude	Baseline and and 1st day 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.