Three New Ideas to Protect Special Forces From the Stress of High Altitude
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 4 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Quercetin Quercetin: 500mg pill, twice daily for 5 days |
Dietary Supplement: Quercetin
|
Experimental: Nifedipine+Methazolamide Nifedipine extended release: 30mg pill, twice daily for 5 days; Methazolamide: 125mg pill, twice daily for 5 days |
Drug: Nifedipine extended release
Drug: Methazolamide
|
Experimental: Metformin Metformin: 500mg pill, once daily for 2 days, then 500mg twice daily at altitude (3 days) |
Drug: Metformin
|
Placebo Comparator: Placebo Sugar pill manufactured to look like all other investigational products |
Drug: Placebo
|
Experimental: Nitrite Nitrite: 20mg pill, three times daily for 5 days |
Drug: Nitrite
|
Outcome Measures
Primary Outcome Measures
- 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.
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Alma College | Alma | Michigan | United States | 48801 |
Sponsors and Collaborators
- University of Colorado, Denver
- Alma College
Investigators
- Principal Investigator: Robert Roach, PhD, University of Colorado Anschutz Medical Campus, Altitude Research Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 15-0254
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail | 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. |
Arm/Group Title | Quercetin | Nifedipine+Methazolamide | Metformin | Placebo | Nitrite |
---|---|---|---|---|---|
Arm/Group Description | Quercetin: 500mg pill, twice daily for 5 days Quercetin | Nifedipine extended release: 30mg pill, twice daily for 5 days; Methazolamide: 125mg pill, twice daily for 5 days Nifedipine extended release Methazolamide | Metformin: 500mg pill, once daily for 2 days, then 500mg twice daily at altitude (3 days) Metformin | Sugar pill manufactured to look like all other investigational products Placebo | Nitrite: 20mg pill, three times daily for 5 days Nitrite |
Period Title: Overall Study | |||||
STARTED | 20 | 20 | 20 | 19 | 20 |
COMPLETED | 19 | 20 | 20 | 19 | 19 |
NOT COMPLETED | 1 | 0 | 0 | 0 | 1 |
Baseline Characteristics
Arm/Group Title | Quercetin | Nifedipine+Methazolamide | Metformin | Placebo | Nitrite | Total |
---|---|---|---|---|---|---|
Arm/Group Description | Quercetin: 500mg pill, twice daily for 5 days Quercetin | Nifedipine extended release: 30mg pill, twice daily for 5 days; Methazolamide: 125mg pill, twice daily for 5 days Nifedipine extended release Methazolamide | Metformin: 500mg pill, once daily for 2 days, then 500mg twice daily at altitude (3 days) Metformin | Sugar pill manufactured to look like all other investigational products Placebo | Nitrite: 20mg pill, three times daily for 5 days Nitrite | Total of all reporting groups |
Overall Participants | 20 | 20 | 20 | 19 | 20 | 99 |
Age (Count of Participants) | ||||||
<=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Between 18 and 65 years |
20
100%
|
20
100%
|
20
100%
|
19
100%
|
20
100%
|
99
100%
|
>=65 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Age (years) [Mean (Standard Deviation) ] | ||||||
Mean (Standard Deviation) [years] |
22.6
(3.0)
|
21.9
(2.6)
|
21.7
(2.0)
|
21.3
(1.4)
|
22.0
(2.1)
|
21.9
(2.27)
|
Sex: Female, Male (Count of Participants) | ||||||
Female |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Male |
20
100%
|
20
100%
|
20
100%
|
19
100%
|
20
100%
|
99
100%
|
Region of Enrollment (participants) [Number] | ||||||
United States |
20
100%
|
20
100%
|
20
100%
|
19
100%
|
20
100%
|
99
100%
|
Outcome Measures
Title | Change in Environmental Symptoms Questionnaire at High Altitude |
---|---|
Description | 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) |
Outcome Measure Data
Analysis Population Description |
---|
Two participants who withdrew from the study were not analyzed. |
Arm/Group Title | Quercetin | Nifedipine+Methazolamide | Metformin | Placebo | Nitrite |
---|---|---|---|---|---|
Arm/Group Description | Quercetin: 500mg pill, twice daily for 5 days Quercetin | Nifedipine extended release: 30mg pill, twice daily for 5 days; Methazolamide: 125mg pill, twice daily for 5 days Nifedipine extended release Methazolamide | Metformin: 500mg pill, once daily for 2 days, then 500mg twice daily at altitude (3 days) Metformin | Sugar pill manufactured to look like all other investigational products Placebo | Nitrite: 20mg pill, three times daily for 5 days Nitrite |
Measure Participants | 19 | 19 | 20 | 19 | 20 |
Baseline |
0.132
(0.179)
|
0.122
(0.214)
|
0.080
(0.132)
|
0.069
(0.109)
|
0.121
(0.240)
|
Change at 3 days |
-0.088
(0.214)
|
-0.073
(0.224)
|
0.128
(0.425)
|
0.035
(0.184)
|
0.044
(0.380)
|
Title | Change in Lake Louise AMS Scoring System at High Altitude |
---|---|
Description | 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) |
Outcome Measure Data
Analysis Population Description |
---|
Two participants who withdrew from the study were not analyzed. |
Arm/Group Title | Quercetin | Nifedipine+Methazolamide | Metformin | Placebo | Nitrite |
---|---|---|---|---|---|
Arm/Group Description | Quercetin: 500mg pill, twice daily for 5 days Quercetin | Nifedipine extended release: 30mg pill, twice daily for 5 days; Methazolamide: 125mg pill, twice daily for 5 days Nifedipine extended release Methazolamide | Metformin: 500mg pill, once daily for 2 days, then 500mg twice daily at altitude (3 days) Metformin | Sugar pill manufactured to look like all other investigational products Placebo | Nitrite: 20mg pill, three times daily for 5 days Nitrite |
Measure Participants | 19 | 19 | 20 | 19 | 20 |
Baseline |
0.00
(0.00)
|
0.150
(0.489)
|
0.150
(0.671)
|
0.00
(0.00)
|
0.250
(1.118)
|
Change at Day 3 |
0.053
(0.229)
|
0.150
(0.875)
|
0.750
(2.124)
|
0.632
(1.012)
|
0.474
(1.896)
|
Title | Change in Army Physical Fitness Test (APFT) at High Altitude |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
Two participants who withdrew from the study were not analyzed. |
Arm/Group Title | Quercetin | Nifedipine+Methazolamide | Metformin | Placebo | Nitrite |
---|---|---|---|---|---|
Arm/Group Description | Quercetin: 500mg pill, twice daily for 5 days Quercetin | Nifedipine extended release: 30mg pill, twice daily for 5 days; Methazolamide: 125mg pill, twice daily for 5 days Nifedipine extended release Methazolamide | Metformin: 500mg pill, once daily for 2 days, then 500mg twice daily at altitude (3 days) Metformin | Sugar pill manufactured to look like all other investigational products Placebo | Nitrite: 20mg pill, three times daily for 5 days Nitrite |
Measure Participants | 19 | 19 | 20 | 19 | 20 |
Baseline |
247.2
(25.1)
|
251.0
(29.4)
|
254.1
(26.9)
|
251.5
(23.9)
|
252.1
(24.9)
|
Change at Day 1 |
-27.5
(23.1)
|
-59.2
(22.7)
|
-32.9
(20.5)
|
-23.0
(27.0)
|
-26.1
(20.3)
|
Title | Change in Uphill Hike at High Altitude |
---|---|
Description | Timed 3.1 mile uphill run/hike, with weighted back-pack |
Time Frame | 2nd day at altitude |
Outcome Measure Data
Analysis Population Description |
---|
Two participants who withdrew from the study were not analyzed. |
Arm/Group Title | Quercetin | Nifedipine+Methazolamide | Metformin | Placebo | Nitrite |
---|---|---|---|---|---|
Arm/Group Description | Quercetin: 500mg pill, twice daily for 5 days Quercetin | Nifedipine extended release: 30mg pill, twice daily for 5 days; Methazolamide: 125mg pill, twice daily for 5 days Nifedipine extended release Methazolamide | Metformin: 500mg pill, once daily for 2 days, then 500mg twice daily at altitude (3 days) Metformin | Sugar pill manufactured to look like all other investigational products Placebo | Nitrite: 20mg pill, three times daily for 5 days Nitrite |
Measure Participants | 19 | 19 | 20 | 19 | 20 |
Mean (Standard Deviation) [seconds] |
4685
(364.4)
|
4993
(595.4)
|
5005
(975.9)
|
4819
(685.1)
|
4953
(670.5)
|
Title | Change in Defense Automated Neurobehavioral Assessment (DANA) Reaction Time at High Altitude |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
Seven participants were not analyzed due to lack of data collection at baseline. |
Arm/Group Title | Quercetin | Nifedipine+Methazolamide | Metformin | Placebo | Nitrite |
---|---|---|---|---|---|
Arm/Group Description | Quercetin: 500mg pill, twice daily for 5 days Quercetin | Nifedipine extended release: 30mg pill, twice daily for 5 days; Methazolamide: 125mg pill, twice daily for 5 days Nifedipine extended release Methazolamide | Metformin: 500mg pill, once daily for 2 days, then 500mg twice daily at altitude (3 days) Metformin | Sugar pill manufactured to look like all other investigational products Placebo | Nitrite: 20mg pill, three times daily for 5 days Nitrite |
Measure Participants | 17 | 19 | 19 | 17 | 18 |
Baseline |
308.0
(34.7)
|
302.2
(49.5)
|
312.3
(46.1)
|
333.9
(41.5)
|
310.7
(29.32)
|
Change from baseline at day 1 |
-0.5
(27.8)
|
14.2
(26.6)
|
-8.3
(37.9)
|
0.5
(30.6)
|
-4.6
(30.8)
|
Adverse Events
Time Frame | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|
Adverse Event Reporting Description | ||||||||||
Arm/Group Title | Quercetin | Nifedipine+Methazolamide | Metformin | Placebo | Nitrite | |||||
Arm/Group Description | Quercetin: 500mg pill, twice daily for 5 days Quercetin | Nifedipine extended release: 30mg pill, twice daily for 5 days; Methazolamide: 125mg pill, twice daily for 5 days Nifedipine extended release Methazolamide | Metformin: 500mg pill, once daily for 2 days, then 500mg twice daily at altitude (3 days) Metformin | Sugar pill manufactured to look like all other investigational products Placebo | Nitrite: 20mg pill, three times daily for 5 days Nitrite | |||||
All Cause Mortality |
||||||||||
Quercetin | Nifedipine+Methazolamide | Metformin | Placebo | Nitrite | ||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/20 (0%) | 0/20 (0%) | 0/20 (0%) | 0/19 (0%) | 0/20 (0%) | |||||
Serious Adverse Events |
||||||||||
Quercetin | Nifedipine+Methazolamide | Metformin | Placebo | Nitrite | ||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/20 (0%) | 0/20 (0%) | 0/20 (0%) | 0/19 (0%) | 0/20 (0%) | |||||
Other (Not Including Serious) Adverse Events |
||||||||||
Quercetin | Nifedipine+Methazolamide | Metformin | Placebo | Nitrite | ||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 1/20 (5%) | 0/20 (0%) | 2/20 (10%) | 1/19 (5.3%) | 1/20 (5%) | |||||
Gastrointestinal disorders | ||||||||||
Vomiting | 1/20 (5%) | 1 | 1/20 (5%) | 1 | 0/20 (0%) | 0 | 1/19 (5.3%) | 1 | 1/20 (5%) | 1 |
General disorders | ||||||||||
Dehydration | 0/20 (0%) | 0 | 0/20 (0%) | 0 | 1/20 (5%) | 1 | 1/19 (5.3%) | 1 | 0/20 (0%) | 0 |
Infections and infestations | ||||||||||
URI/ILI (Flu-like illness) | 1/20 (5%) | 20 | 1/20 (5%) | 20 | 0/20 (0%) | 0 | 0/19 (0%) | 0 | 0/20 (0%) | 0 |
Psychiatric disorders | ||||||||||
Anxiety attack | 0/20 (0%) | 0 | 0/20 (0%) | 0 | 1/20 (5%) | 1 | 0/19 (0%) | 0 | 0/20 (0%) | 0 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | Robert Roach |
---|---|
Organization | University of Colorado Denver |
Phone | |
clinicalresearchsupportcenter@ucdenver.edu |
- 15-0254