Rapid Acclimatization to Hypoxia at Altitude

Phase 1

Completed

Interventions: Drug: Aminophylline+Methazolamide
Drug: Placebo
Drug: Methazolamide
Drug: Aminophylline

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.

Recruitment & Eligibility

Inclusion Criteria

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.

Arm && Interventions

Group	Intervention	Description
Aminophylline+Methazolamide	Aminophylline+Methazolamide	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.
Placebo	Placebo	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.
Methazolamide	Methazolamide	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.
Aminophylline	Aminophylline	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.

Primary Outcome Measures

Name	Time	Method
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.

Secondary Outcome Measures