Trial Outcomes & Findings for Three New Ideas to Protect Special Forces From the Stress of High Altitude (NCT NCT02463357)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

148 participants

Primary outcome timeframe

Baseline and during high altitude exposure (3 days, AM/PM)

Results posted on

2021-03-30

Participant Flow

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.

Participant milestones

Participant milestones
Measure	Quercetin Quercetin: 500mg pill, twice daily for 5 days Quercetin	Nifedipine+Methazolamide Nifedipine extended release: 30mg pill, twice daily for 5 days; Methazolamide: 125mg pill, twice daily for 5 days Nifedipine extended release Methazolamide	Metformin Metformin: 500mg pill, once daily for 2 days, then 500mg twice daily at altitude (3 days) Metformin	Placebo Sugar pill manufactured to look like all other investigational products Placebo	Nitrite Nitrite: 20mg pill, three times daily for 5 days Nitrite
Overall Study STARTED	20	20	20	19	20
Overall Study COMPLETED	19	20	20	19	19
Overall Study NOT COMPLETED	1	0	0	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Quercetin Quercetin: 500mg pill, twice daily for 5 days Quercetin	Nifedipine+Methazolamide Nifedipine extended release: 30mg pill, twice daily for 5 days; Methazolamide: 125mg pill, twice daily for 5 days Nifedipine extended release Methazolamide	Metformin Metformin: 500mg pill, once daily for 2 days, then 500mg twice daily at altitude (3 days) Metformin	Placebo Sugar pill manufactured to look like all other investigational products Placebo	Nitrite Nitrite: 20mg pill, three times daily for 5 days Nitrite
Overall Study Withdrawal by Subject	0	0	0	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Quercetin n=20 Participants Quercetin: 500mg pill, twice daily for 5 days Quercetin	Nifedipine+Methazolamide n=20 Participants Nifedipine extended release: 30mg pill, twice daily for 5 days; Methazolamide: 125mg pill, twice daily for 5 days Nifedipine extended release Methazolamide	Metformin n=20 Participants Metformin: 500mg pill, once daily for 2 days, then 500mg twice daily at altitude (3 days) Metformin	Placebo n=19 Participants Sugar pill manufactured to look like all other investigational products Placebo	Nitrite n=20 Participants Nitrite: 20mg pill, three times daily for 5 days Nitrite	Total n=99 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Age, Categorical Between 18 and 65 years	20 Participants n=5 Participants	20 Participants n=7 Participants	20 Participants n=5 Participants	19 Participants n=4 Participants	20 Participants n=21 Participants	99 Participants n=10 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Age, Continuous	22.6 years STANDARD_DEVIATION 3.0 • n=5 Participants	21.9 years STANDARD_DEVIATION 2.6 • n=7 Participants	21.7 years STANDARD_DEVIATION 2.0 • n=5 Participants	21.3 years STANDARD_DEVIATION 1.4 • n=4 Participants	22.0 years STANDARD_DEVIATION 2.1 • n=21 Participants	21.9 years STANDARD_DEVIATION 2.27 • n=10 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Sex: Female, Male Male	20 Participants n=5 Participants	20 Participants n=7 Participants	20 Participants n=5 Participants	19 Participants n=4 Participants	20 Participants n=21 Participants	99 Participants n=10 Participants
Region of Enrollment United States	20 participants n=5 Participants	20 participants n=7 Participants	20 participants n=5 Participants	19 participants n=4 Participants	20 participants n=21 Participants	99 participants n=10 Participants

PRIMARY outcome

Timeframe: Baseline and during high altitude exposure (3 days, AM/PM)

Population: Two participants who withdrew from the study were not analyzed.

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.

Outcome measures

Outcome measures
Measure	Quercetin n=19 Participants Quercetin: 500mg pill, twice daily for 5 days Quercetin	Nifedipine+Methazolamide n=19 Participants Nifedipine extended release: 30mg pill, twice daily for 5 days; Methazolamide: 125mg pill, twice daily for 5 days Nifedipine extended release Methazolamide	Metformin n=20 Participants Metformin: 500mg pill, once daily for 2 days, then 500mg twice daily at altitude (3 days) Metformin	Placebo n=19 Participants Sugar pill manufactured to look like all other investigational products Placebo	Nitrite n=20 Participants Nitrite: 20mg pill, three times daily for 5 days Nitrite
Change in Environmental Symptoms Questionnaire at High Altitude Baseline	0.132 score on a scale Standard Deviation 0.179	0.122 score on a scale Standard Deviation 0.214	0.080 score on a scale Standard Deviation 0.132	0.069 score on a scale Standard Deviation 0.109	0.121 score on a scale Standard Deviation 0.240
Change in Environmental Symptoms Questionnaire at High Altitude Change at 3 days	-0.088 score on a scale Standard Deviation 0.214	-0.073 score on a scale Standard Deviation 0.224	0.128 score on a scale Standard Deviation 0.425	0.035 score on a scale Standard Deviation 0.184	0.044 score on a scale Standard Deviation 0.380

PRIMARY outcome

Timeframe: Baseline and during high altitude exposure (3 days, AM/PM)

Population: Two participants who withdrew from the study were not analyzed.

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.

Outcome measures

Outcome measures
Measure	Quercetin n=19 Participants Quercetin: 500mg pill, twice daily for 5 days Quercetin	Nifedipine+Methazolamide n=19 Participants Nifedipine extended release: 30mg pill, twice daily for 5 days; Methazolamide: 125mg pill, twice daily for 5 days Nifedipine extended release Methazolamide	Metformin n=20 Participants Metformin: 500mg pill, once daily for 2 days, then 500mg twice daily at altitude (3 days) Metformin	Placebo n=19 Participants Sugar pill manufactured to look like all other investigational products Placebo	Nitrite n=20 Participants Nitrite: 20mg pill, three times daily for 5 days Nitrite
Change in Lake Louise AMS Scoring System at High Altitude Baseline	0.00 score on a scale Standard Deviation 0.00	0.150 score on a scale Standard Deviation 0.489	0.150 score on a scale Standard Deviation 0.671	0.00 score on a scale Standard Deviation 0.00	0.250 score on a scale Standard Deviation 1.118
Change in Lake Louise AMS Scoring System at High Altitude Change at Day 3	0.053 score on a scale Standard Deviation 0.229	0.150 score on a scale Standard Deviation 0.875	0.750 score on a scale Standard Deviation 2.124	0.632 score on a scale Standard Deviation 1.012	0.474 score on a scale Standard Deviation 1.896

PRIMARY outcome

Timeframe: Baseline, 1st day at high altitude

Population: Two participants who withdrew from the study were not analyzed.

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.

Outcome measures

Outcome measures
Measure	Quercetin n=19 Participants Quercetin: 500mg pill, twice daily for 5 days Quercetin	Nifedipine+Methazolamide n=19 Participants Nifedipine extended release: 30mg pill, twice daily for 5 days; Methazolamide: 125mg pill, twice daily for 5 days Nifedipine extended release Methazolamide	Metformin n=20 Participants Metformin: 500mg pill, once daily for 2 days, then 500mg twice daily at altitude (3 days) Metformin	Placebo n=19 Participants Sugar pill manufactured to look like all other investigational products Placebo	Nitrite n=20 Participants Nitrite: 20mg pill, three times daily for 5 days Nitrite
Change in Army Physical Fitness Test (APFT) at High Altitude Baseline	247.2 score on a scale Standard Deviation 25.1	251.0 score on a scale Standard Deviation 29.4	254.1 score on a scale Standard Deviation 26.9	251.5 score on a scale Standard Deviation 23.9	252.1 score on a scale Standard Deviation 24.9
Change in Army Physical Fitness Test (APFT) at High Altitude Change at Day 1	-27.5 score on a scale Standard Deviation 23.1	-59.2 score on a scale Standard Deviation 22.7	-32.9 score on a scale Standard Deviation 20.5	-23.0 score on a scale Standard Deviation 27.0	-26.1 score on a scale Standard Deviation 20.3

PRIMARY outcome

Timeframe: 2nd day at altitude

Population: Two participants who withdrew from the study were not analyzed.

Timed 3.1 mile uphill run/hike, with weighted back-pack

Outcome measures

Outcome measures
Measure	Quercetin n=19 Participants Quercetin: 500mg pill, twice daily for 5 days Quercetin	Nifedipine+Methazolamide n=19 Participants Nifedipine extended release: 30mg pill, twice daily for 5 days; Methazolamide: 125mg pill, twice daily for 5 days Nifedipine extended release Methazolamide	Metformin n=20 Participants Metformin: 500mg pill, once daily for 2 days, then 500mg twice daily at altitude (3 days) Metformin	Placebo n=19 Participants Sugar pill manufactured to look like all other investigational products Placebo	Nitrite n=20 Participants Nitrite: 20mg pill, three times daily for 5 days Nitrite
Change in Uphill Hike at High Altitude	4685 seconds Standard Deviation 364.4	4993 seconds Standard Deviation 595.4	5005 seconds Standard Deviation 975.9	4819 seconds Standard Deviation 685.1	4953 seconds Standard Deviation 670.5

PRIMARY outcome

Timeframe: Baseline and and 1st day at high altitude

Population: Seven participants were not analyzed due to lack of data collection at baseline.

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.