Mountain Sickness
Conditions
Keywords
Exercise, Aerobic, Cognitive Function
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.
Interventions
Sponsors
Alma College
University of Colorado, Denver
Study design
Allocation
NON_RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to 30 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Pre-assignment details
49 participants were excluded after consent/enrollment but prior to starting the study because some subjects did not meet baseline criteria, and others had to be excluded due to resource limitations.
Participants by arm
| Arm | Count |
|---|---|
| Quercetin Quercetin: 500mg pill, twice daily for 5 days
Quercetin | 20 |
| Nifedipine+Methazolamide Nifedipine extended release: 30mg pill, twice daily for 5 days; Methazolamide: 125mg pill, twice daily for 5 days
Nifedipine extended release
Methazolamide | 20 |
| Metformin Metformin: 500mg pill, once daily for 2 days, then 500mg twice daily at altitude (3 days)
Metformin | 20 |
| Placebo Sugar pill manufactured to look like all other investigational products
Placebo | 19 |
| Nitrite Nitrite: 20mg pill, three times daily for 5 days
Nitrite | 20 |
| Total | 99 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Nifedipine+Methazolamide | Metformin | Placebo | Quercetin | Nitrite | Total |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants | 20 Participants | 19 Participants | 20 Participants | 20 Participants | 99 Participants |
| Age, Continuous | 21.9 years STANDARD_DEVIATION 2.6 | 21.7 years STANDARD_DEVIATION 2 | 21.3 years STANDARD_DEVIATION 1.4 | 22.6 years STANDARD_DEVIATION 3 | 22.0 years STANDARD_DEVIATION 2.1 | 21.9 years STANDARD_DEVIATION 2.27 |
| Region of Enrollment United States | 20 participants | 20 participants | 19 participants | 20 participants | 20 participants | 99 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 20 Participants | 20 Participants | 19 Participants | 20 Participants | 20 Participants | 99 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 | 0 / 20 | 0 / 19 | 0 / 20 |
| other Total, other adverse events | 1 / 20 | 0 / 20 | 2 / 20 | 1 / 19 | 1 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 | 0 / 20 | 0 / 19 | 0 / 20 |
Outcome results
Primary
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.
Time frame: Baseline, 1st day at high altitude
Population: Two participants who withdrew from the study were not analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Quercetin | Change in Army Physical Fitness Test (APFT) at High Altitude | Baseline | 247.2 score on a scale | Standard Deviation 25.1 |
| Quercetin | Change in Army Physical Fitness Test (APFT) at High Altitude | Change at Day 1 | -27.5 score on a scale | Standard Deviation 23.1 |
| Nifedipine+Methazolamide | Change in Army Physical Fitness Test (APFT) at High Altitude | Baseline | 251.0 score on a scale | Standard Deviation 29.4 |
| Nifedipine+Methazolamide | Change in Army Physical Fitness Test (APFT) at High Altitude | Change at Day 1 | -59.2 score on a scale | Standard Deviation 22.7 |
| Metformin | Change in Army Physical Fitness Test (APFT) at High Altitude | Baseline | 254.1 score on a scale | Standard Deviation 26.9 |
| Metformin | Change in Army Physical Fitness Test (APFT) at High Altitude | Change at Day 1 | -32.9 score on a scale | Standard Deviation 20.5 |
| Placebo | Change in Army Physical Fitness Test (APFT) at High Altitude | Change at Day 1 | -23.0 score on a scale | Standard Deviation 27 |
| Placebo | Change in Army Physical Fitness Test (APFT) at High Altitude | Baseline | 251.5 score on a scale | Standard Deviation 23.9 |
| Nitrite | Change in Army Physical Fitness Test (APFT) at High Altitude | Baseline | 252.1 score on a scale | Standard Deviation 24.9 |
| Nitrite | Change in Army Physical Fitness Test (APFT) at High Altitude | Change at Day 1 | -26.1 score on a scale | Standard Deviation 20.3 |
Primary
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.
Time frame: Baseline and and 1st day at high altitude
Population: Seven participants were not analyzed due to lack of data collection at baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Quercetin | Change in Defense Automated Neurobehavioral Assessment (DANA) Reaction Time at High Altitude | Change from baseline at day 1 | -0.5 milliseconds | Standard Deviation 27.8 |
| Quercetin | Change in Defense Automated Neurobehavioral Assessment (DANA) Reaction Time at High Altitude | Baseline | 308.0 milliseconds | Standard Deviation 34.7 |
| Nifedipine+Methazolamide | Change in Defense Automated Neurobehavioral Assessment (DANA) Reaction Time at High Altitude | Change from baseline at day 1 | 14.2 milliseconds | Standard Deviation 26.6 |
| Nifedipine+Methazolamide | Change in Defense Automated Neurobehavioral Assessment (DANA) Reaction Time at High Altitude | Baseline | 302.2 milliseconds | Standard Deviation 49.5 |
| Metformin | Change in Defense Automated Neurobehavioral Assessment (DANA) Reaction Time at High Altitude | Baseline | 312.3 milliseconds | Standard Deviation 46.1 |
| Metformin | Change in Defense Automated Neurobehavioral Assessment (DANA) Reaction Time at High Altitude | Change from baseline at day 1 | -8.3 milliseconds | Standard Deviation 37.9 |
| Placebo | Change in Defense Automated Neurobehavioral Assessment (DANA) Reaction Time at High Altitude | Baseline | 333.9 milliseconds | Standard Deviation 41.5 |
| Placebo | Change in Defense Automated Neurobehavioral Assessment (DANA) Reaction Time at High Altitude | Change from baseline at day 1 | 0.5 milliseconds | Standard Deviation 30.6 |
| Nitrite | Change in Defense Automated Neurobehavioral Assessment (DANA) Reaction Time at High Altitude | Change from baseline at day 1 | -4.6 milliseconds | Standard Deviation 30.8 |
| Nitrite | Change in Defense Automated Neurobehavioral Assessment (DANA) Reaction Time at High Altitude | Baseline | 310.7 milliseconds | Standard Deviation 29.32 |
Primary
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.
Time frame: Baseline and during high altitude exposure (3 days, AM/PM)
Population: Two participants who withdrew from the study were not analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Quercetin | Change in Environmental Symptoms Questionnaire at High Altitude | Baseline | 0.132 score on a scale | Standard Deviation 0.179 |
| Quercetin | Change in Environmental Symptoms Questionnaire at High Altitude | Change at 3 days | -0.088 score on a scale | Standard Deviation 0.214 |
| Nifedipine+Methazolamide | Change in Environmental Symptoms Questionnaire at High Altitude | Baseline | 0.122 score on a scale | Standard Deviation 0.214 |
| Nifedipine+Methazolamide | Change in Environmental Symptoms Questionnaire at High Altitude | Change at 3 days | -0.073 score on a scale | Standard Deviation 0.224 |
| Metformin | Change in Environmental Symptoms Questionnaire at High Altitude | Baseline | 0.080 score on a scale | Standard Deviation 0.132 |
| Metformin | Change in Environmental Symptoms Questionnaire at High Altitude | Change at 3 days | 0.128 score on a scale | Standard Deviation 0.425 |
| Placebo | Change in Environmental Symptoms Questionnaire at High Altitude | Change at 3 days | 0.035 score on a scale | Standard Deviation 0.184 |
| Placebo | Change in Environmental Symptoms Questionnaire at High Altitude | Baseline | 0.069 score on a scale | Standard Deviation 0.109 |
| Nitrite | Change in Environmental Symptoms Questionnaire at High Altitude | Baseline | 0.121 score on a scale | Standard Deviation 0.24 |
| Nitrite | Change in Environmental Symptoms Questionnaire at High Altitude | Change at 3 days | 0.044 score on a scale | Standard Deviation 0.38 |
Primary
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.
Time frame: Baseline and during high altitude exposure (3 days, AM/PM)
Population: Two participants who withdrew from the study were not analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Quercetin | Change in Lake Louise AMS Scoring System at High Altitude | Baseline | 0.00 score on a scale | Standard Deviation 0 |
| Quercetin | Change in Lake Louise AMS Scoring System at High Altitude | Change at Day 3 | 0.053 score on a scale | Standard Deviation 0.229 |
| Nifedipine+Methazolamide | Change in Lake Louise AMS Scoring System at High Altitude | Baseline | 0.150 score on a scale | Standard Deviation 0.489 |
| Nifedipine+Methazolamide | Change in Lake Louise AMS Scoring System at High Altitude | Change at Day 3 | 0.150 score on a scale | Standard Deviation 0.875 |
| Metformin | Change in Lake Louise AMS Scoring System at High Altitude | Baseline | 0.150 score on a scale | Standard Deviation 0.671 |
| Metformin | Change in Lake Louise AMS Scoring System at High Altitude | Change at Day 3 | 0.750 score on a scale | Standard Deviation 2.124 |
| Placebo | Change in Lake Louise AMS Scoring System at High Altitude | Change at Day 3 | 0.632 score on a scale | Standard Deviation 1.012 |
| Placebo | Change in Lake Louise AMS Scoring System at High Altitude | Baseline | 0.00 score on a scale | Standard Deviation 0 |
| Nitrite | Change in Lake Louise AMS Scoring System at High Altitude | Baseline | 0.250 score on a scale | Standard Deviation 1.118 |
| Nitrite | Change in Lake Louise AMS Scoring System at High Altitude | Change at Day 3 | 0.474 score on a scale | Standard Deviation 1.896 |
Primary
Change in Uphill Hike at High Altitude
Timed 3.1 mile uphill run/hike, with weighted back-pack
Time frame: 2nd day at altitude
Population: Two participants who withdrew from the study were not analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Quercetin | Change in Uphill Hike at High Altitude | 4685 seconds | Standard Deviation 364.4 |
| Nifedipine+Methazolamide | Change in Uphill Hike at High Altitude | 4993 seconds | Standard Deviation 595.4 |
| Metformin | Change in Uphill Hike at High Altitude | 5005 seconds | Standard Deviation 975.9 |
| Placebo | Change in Uphill Hike at High Altitude | 4819 seconds | Standard Deviation 685.1 |
| Nitrite | Change in Uphill Hike at High Altitude | 4953 seconds | Standard Deviation 670.5 |