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

NCT02463357 | Completed Phase 4 Results DMC

• 1 other identifier: 15-0254
• Study Type: interventional
• Target: 148
• Locations: 1 country
• Sites: 1

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.

Conditions

Mountain Sickness

Keywords

Exercise, Aerobic; Cognitive Function

Outcome Measures

Primary Outcomes (5)

• 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

Study Arms (5)

Quercetin

EXPERIMENTAL

Quercetin: 500mg pill, twice daily for 5 days

Dietary Supplement: Quercetin

Nifedipine+Methazolamide

EXPERIMENTAL

Nifedipine extended release: 30mg pill, twice daily for 5 days; Methazolamide: 125mg pill, twice daily for 5 days

Drug: Nifedipine extended release; Drug: Methazolamide

Metformin

EXPERIMENTAL

Metformin: 500mg pill, once daily for 2 days, then 500mg twice daily at altitude (3 days)

Drug: Metformin

Placebo

PLACEBO COMPARATOR

Sugar pill manufactured to look like all other investigational products

Drug: Placebo

Nitrite

EXPERIMENTAL

Nitrite: 20mg pill, three times daily for 5 days

Drug: Nitrite

Interventions

Quercetin DIETARY_SUPPLEMENT

Quercetin

Nifedipine extended release DRUG

Nifedipine+Methazolamide

Methazolamide DRUG

Nifedipine+Methazolamide

Metformin DRUG

Metformin

Placebo DRUG

Placebo

Nitrite DRUG

Nitrite

Eligibility Criteria

• Age: 18 Years - 30 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Colorado, Denver: lead
• Alma College: collaborator

Study Sites (1)

Alma College

Alma, Michigan, 48801, United States

Location

MeSH Terms

Conditions

Altitude Sickness; Motor Activity

Interventions

Quercetin; Methazolamide; Metformin; Nitrites

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases; Behavior

Intervention Hierarchy (Ancestors)

Flavonols; Flavonoids; Chromones; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Thiadiazoles; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Biguanides; Guanidines; Amidines; Anions; Ions; Electrolytes; Inorganic Chemicals; Nitrous Acid; Nitrogen Compounds

Results Point of Contact

• Title: Robert Roach
• Organization: University of Colorado Denver

clinicalresearchsupportcenter@ucdenver.edu

Study Officials

• Robert Roach, PhD

  University of Colorado Anschutz Medical Campus, Altitude Research Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 29, 2015
• First Posted: June 4, 2015
• Study Start: August 1, 2015
• Primary Completion: September 1, 2016
• Study Completion: September 1, 2016
• Last Updated: March 30, 2021
• Results First Posted: March 30, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)