Rapid Acclimatization to Hypoxia at Altitude

Study Overview
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Brief Summary
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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.

Official Title
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Rapid Acclimatization to Hypoxia at Altitude

Conditions
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Physiological Function in Low Oxygen Environment

Intervention / Treatment
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* Drug: Placebo
* Drug: Aminophylline
* Drug: Methazolamide
* Drug: Aminophylline+Methazolamide


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Administer a single dose of placebo (yellow corn meal in a capsule, gelatin ) in Normoxic Conditions. Following a minimum of 7 days a single dose placebo will be administered (yellow corn meal in a gelatin capsule) in Hypoxic conditions. | Drug: Placebo<br>* Yellow corn meal in gel capsules<br>* Other names: Yellow corn meal;|
| Active Comparator: Aminophylline<br>Administer a single dose of 400 mg Aminophylline (4-100 mg tablets) in Normoxic Conditions. Following a minimum of 7 days administer a single dose of 400 mg Aminophylline (4-100 mg tablets) in Hypoxic conditions. | Drug: Aminophylline<br>* National Drug Code (NDC) 0143-1020-01<br>* Other names: Theophylline;|
| Active Comparator: Methazolamide<br>Administer a single dose of 250 mg Methazolamide (10-25 mg tablets) in Normoxic Conditions. Following a minimum of 7 days administer a single dose of 250 mg Methazolamide (10-25 mg tablets) in Hypoxic conditions. | Drug: Methazolamide<br>* NDC 0781-1072-01<br>* Other names: Neptazane;|
| Active Comparator: Aminophylline+Methazolamide<br>Administer a single dose of 400 mg Aminophylline (4-100 mg tablets) + 250 mg Methazolamide (10-25 mg tablets) in Normoxic Conditions.(Aminophylline+Methazolamide) Following a minimum of 7 days administer a single dose of 400 mg Aminophylline (4-100 mg tablets) + 250 mg Methazolamide (10-25 mg tablets) in Hypoxic conditions. | Drug: Aminophylline+Methazolamide<br>* NDC 0143-1020-01 and NDC 0781-1072-01<br>* Other names: Theophylline + Neptazane;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | The exercise trial will begin within 5 hours of exposure to either normoxia or hypoxia | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypoxia, Altitude, Exercise