Effect of Acetazolamide and Methazolamide on Hypoxic Exercise Performance

Overview

A single-centered randomized doubled blinded placebo-controlled cross-over trial comparing two the effect of two carbonic anhydrase inhibitors on exercise performance in acute hypoxia. Participants will be young (under 40 years of age), healthy males and females who are regularly physically active.

Study Type

• Study Type: Interventional
• Study Design
  • Allocation: Randomized
  • Intervention Model: Crossover Assignment
  • Primary Purpose: Basic Science
  • Masking: Double (Participant, Investigator)
• Study Primary Completion Date: September 2023

Interventions

• Drug: Acetazolamide 250Mg Tab
  • Oral acetazolamide
• Drug: Methazolamide Pill
  • Oral Methazolamide
• Drug: Placebo
  • Oral placebo

Arms, Groups and Cohorts

• Experimental: Methazolamide
  • Drug: Methazolamide Dose: 100 mg b.i.d Duration: 2 days prior to testing + 1 hr prior to testing start Form: Oral
• Active Comparator: Acetazolamide
  • Drug: Acetazolamide Dose: 250 mg t.i.d Duration: 2 days prior to testing + 1 hr prior to testing start Form: Oral
• Placebo Comparator: Placebo
  • Drug: Placebo (microcrystalline cellulose) Dose: 250 mg t.i.d Duration: 2 days prior to testing + 1 hr prior to testing start Form: Oral

Clinical Trial Outcome Measures

Primary Measures

• Time to complete a 5 km time trial after each experimental day (Days 3-5)
  • Time Frame: The time to complete the 5 km time trial is measured after each time trial. The investigators will be blinded until all participants have completed each trial
  • Primary endpoint is the time to complete a 5 km exercise task in the three arms of the trial (acetazolamide, methazolamide, placebo)

Secondary Measures

• Expired Minute Ventilation
  • Time Frame: The average minute ventilation for each time trial km (1-5) for each arm will be determined. The investigators will be blinded until all participants have completed each trial
  • The secondary endpoint expired minute ventilation will be measured using a flow meter (pneumotach) which measure flow and allows for the calculation of ventilation. The value is expressed in liters per min and measured continuously
• Oxyhemoglobin saturation
  • Time Frame: The average oxyhemoglobin saturation for each time trial km (1-5) for each arm will be determined. The investigators will be blinded until all participants have completed each trial
  • The secondary endpoint oxyhemoglobin saturation will be measured using a pulse oximeter which measure the fraction of hemoglobin bound to oxygen. The value is expressed as a percent and measured continuously

Participating in This Clinical Trial

Inclusion Criteria

• Consent provided – Between ages of 18-40 years old – In good general health as evidences by medical history – Perform at least 150 mins of aerobic exercise per week, and engage in physical activity >2 days a week – Completed in an endurance event in the last 12 months – Ability to take oral medication, and be willing to adhere to the drug regimen – Be willing to have blood samples taken Exclusion Criteria:

• Weigh 49kg or less, or are Obese (BMI >30 kg/m2) – Presence of chronic health condition (s), being investigated and/or taking prescription medications for the following disorders: 1. Cardiovascular – e.g., hypertension 2. Metabolic – e.g., type 1 or 2 diabetes 3. Respiratory – e.g., chronic obstructive pulmonary disease, asthma 4. Digestive – e.g., ulcerative colitis 5. Arthritis 6. Cancer – Presence of any disorder or condition listed in the health screening questionnaire (see section 12.1) – Current use of Lonafarnib, Methenamine, Topamax, or steroids/corticosteroids – Known allergic reactions/hypersensitivity to carbonic anhydrase inhibitors or sulfonamides – Presence of bleeding or clotting disorders – Current smoker or cannabis user – Pregnant, suspect to be pregnant, currently planning a pregnancy, or nursing – Any condition or diagnosis, that could in the opinion of the Principal Investigator or delegate interfere with the participant's ability to comply with study instructions, might confound the interpretation of the study results, or put the participant at risk

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 40 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

• Lead Sponsor
  • University of Waterloo
• Collaborator
  • Wilderness Medical Society
• Provider of Information About this Clinical Study
  • Sponsor