Physiological Function in Low Oxygen Environment
Conditions
Keywords
Hypoxia, Altitude, Exercise
Brief summary
In low oxygen environments, such as altitude, some adults may become ill and suffer from acute mountain sickness. Further, all adults will find that exercising becomes much more difficult when compared with exercise at lower altitudes (e.g. sea-level). The purpose of this investigation is to study the effects of two drugs that may help people adjust to high-altitude quickly, prevent them from becoming ill and improve their exercise performance. The drugs are Methazolamide and Aminophylline.
Interventions
DRUGPlacebo
Yellow corn meal in gel capsules
DRUGAminophylline
National Drug Code (NDC) 0143-1020-01
DRUGMethazolamide
NDC 0781-1072-01
DRUGAminophylline+Methazolamide
NDC 0143-1020-01 and NDC 0781-1072-01
Sponsors
Defense Advanced Research Projects Agency
University of Colorado, Denver
Colorado State University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* normotensive (i.e. \<140/90 mmHg)
Exclusion criteria
* Pregnancy * nursing mother * current tobacco use or regular use within the previous two years * use of prescription medication other than birth control * asthma or any other type of lung/respiratory dysfunction * resting oxygen saturation \<95% * unwillingness to abstain from exercise for 48 hours prior to laboratory testing * use of anticoagulant therapy or have a known or suspected bleeding disorder * identification of contraindication during screening (i.e. positive stress test) * any history of mountain sickness (altitude sickness) * any history of allergic reaction, hypersensitivity or idiosyncratic reaction to any of the products administered during the study, including allergy to any sulfa or sulfonamide derivatives * history of clinically significant illness within 4 weeks prior to Day 1 * Subjects who have made any significant donation (including plasma) or have had a significant loss of blood within 30 days prior to visit 1 * receipt of a transfusion or any blood products within 30 days prior to visit 1.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Magnitude of Decrement in Exercise Time Trial Performance in Hypoxia (Low Oxygen) Compared With Normoxia (Normal Oxygen). | The exercise trial will begin within 5 hours of exposure to either normoxia or hypoxia | After exercising on a stationary cycle ergometer for 30 minutes at a resistance of 100 watts, research participants will complete an exercise time trial. The time taken to cycle a distance equivalent to 7.75 miles will be recorded. On a separate day the experiment will be repeated in hypoxia. It is expected that the time taken to cycle a distance equivalent to 7.75 miles will be longer in hypoxia compared to normoxia. One of the goals of this research is to determine if the hypoxia-mediated performance decrement can be decreased with one of our pharmacological interventions. |
Countries
United States
Participant flow
Pre-assignment details
19 individual participants enrolled in the study. Participants were provided with the opportunity to re-enroll and enter additional arm(s).
Participants by arm
| Arm | Count |
|---|---|
| Placebo Single dose Placebo Normoxia Minimum 7 day washout Single dose placebo: Hypoxia | 11 |
| Aminophylline Single dose Aminophylline Normoxia Minimum 7 day washout Single dose Aminophylline Hypoxia | 10 |
| Methazolamide Single dose Methazolamide Normoxia Minimum 7 day washout Single dose Methazolamide: Hypoxia | 10 |
| Aminophylline + Methazolamide Single dose Aminophylline+Methazolamide Normoxia Minimum 7 day washout Single dose Aminophylline+Methazolamide: Hypoxia | 10 |
| Total | 41 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 1 | 0 |
| Overall Study | Equipment failure | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo | Aminophylline | Methazolamide | Aminophylline + Methazolamide | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants | 10 Participants | 10 Participants | 10 Participants | 41 Participants |
| Age, Continuous | 27 years STANDARD_DEVIATION 5 | 26 years STANDARD_DEVIATION 7 | 27 years STANDARD_DEVIATION 6 | 27 years STANDARD_DEVIATION 5 | 27 years STANDARD_DEVIATION 5 |
| Body Fat % | 20.2 Percentage of body fat STANDARD_DEVIATION 3 | 21.4 Percentage of body fat STANDARD_DEVIATION 7 | 20.6 Percentage of body fat STANDARD_DEVIATION 2 | 22.4 Percentage of body fat STANDARD_DEVIATION 7 | 21.1 Percentage of body fat STANDARD_DEVIATION 5 |
| Body Mass Index | 24.8 kg/m^2 STANDARD_DEVIATION 2 | 25.4 kg/m^2 STANDARD_DEVIATION 2 | 25.1 kg/m^2 STANDARD_DEVIATION 2 | 25.4 kg/m^2 STANDARD_DEVIATION 2 | 25.2 kg/m^2 STANDARD_DEVIATION 2 |
| Fat Free Mass | 61.3 kilograms STANDARD_DEVIATION 7 | 60.8 kilograms STANDARD_DEVIATION 8 | 61.9 kilograms STANDARD_DEVIATION 7 | 60.9 kilograms STANDARD_DEVIATION 9 | 61.2 kilograms STANDARD_DEVIATION 7 |
| Fat Mass | 15.4 kilograms STANDARD_DEVIATION 2 | 16.5 kilograms STANDARD_DEVIATION 5 | 16.0 kilograms STANDARD_DEVIATION 2 | 17.4 kilograms STANDARD_DEVIATION 5 | 16.3 kilograms STANDARD_DEVIATION 3 |
| maximal oxygen uptake (VO2max) | 48.7 milliliter/kilogram/minute STANDARD_DEVIATION 8 | 49.4 milliliter/kilogram/minute STANDARD_DEVIATION 10 | 49.8 milliliter/kilogram/minute STANDARD_DEVIATION 8 | 46.5 milliliter/kilogram/minute STANDARD_DEVIATION 8 | 48.6 milliliter/kilogram/minute STANDARD_DEVIATION 8 |
| Region of Enrollment United States | 11 participants | 10 participants | 10 participants | 10 participants | 41 participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 0 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 10 Participants | 9 Participants | 10 Participants | 8 Participants | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 11 | 1 / 10 | 2 / 10 | 4 / 10 |
| serious Total, serious adverse events | 0 / 11 | 0 / 10 | 0 / 10 | 0 / 10 |
Outcome results
Primary
Magnitude of Decrement in Exercise Time Trial Performance in Hypoxia (Low Oxygen) Compared With Normoxia (Normal Oxygen).
After exercising on a stationary cycle ergometer for 30 minutes at a resistance of 100 watts, research participants will complete an exercise time trial. The time taken to cycle a distance equivalent to 7.75 miles will be recorded. On a separate day the experiment will be repeated in hypoxia. It is expected that the time taken to cycle a distance equivalent to 7.75 miles will be longer in hypoxia compared to normoxia. One of the goals of this research is to determine if the hypoxia-mediated performance decrement can be decreased with one of our pharmacological interventions.
Time frame: The exercise trial will begin within 5 hours of exposure to either normoxia or hypoxia
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normoxia Placebo | Magnitude of Decrement in Exercise Time Trial Performance in Hypoxia (Low Oxygen) Compared With Normoxia (Normal Oxygen). | 22.3 minutes | Standard Error 0.7 |
| Hypoxia Placebo | Magnitude of Decrement in Exercise Time Trial Performance in Hypoxia (Low Oxygen) Compared With Normoxia (Normal Oxygen). | 25.2 minutes | Standard Error 1.2 |
| Normoxia Aminophylline | Magnitude of Decrement in Exercise Time Trial Performance in Hypoxia (Low Oxygen) Compared With Normoxia (Normal Oxygen). | 22.2 minutes | Standard Error 0.5 |
| Hypoxia Aminophylline | Magnitude of Decrement in Exercise Time Trial Performance in Hypoxia (Low Oxygen) Compared With Normoxia (Normal Oxygen). | 24.0 minutes | Standard Error 0.7 |
| Normoxia Methazolamide | Magnitude of Decrement in Exercise Time Trial Performance in Hypoxia (Low Oxygen) Compared With Normoxia (Normal Oxygen). | 23.0 minutes | Standard Error 0.5 |
| Hypoxia Methazolamide | Magnitude of Decrement in Exercise Time Trial Performance in Hypoxia (Low Oxygen) Compared With Normoxia (Normal Oxygen). | 24.6 minutes | Standard Error 0.5 |
| Normoxia Methazolamide/Aminophylline | Magnitude of Decrement in Exercise Time Trial Performance in Hypoxia (Low Oxygen) Compared With Normoxia (Normal Oxygen). | 24.5 minutes | Standard Error 0.9 |
| Hypoxia Methazolamide/Aminophylline | Magnitude of Decrement in Exercise Time Trial Performance in Hypoxia (Low Oxygen) Compared With Normoxia (Normal Oxygen). | 25.9 minutes | Standard Error 1 |