Effect of Acetazolamide and Methazolamide on Hypoxic Exercise Performance

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 Overview

• Status: Completed
• Conditions: High Altitude Effects
• Intervention / Treatment: Drug: Placebo; Drug: Methazolamide Pill; Drug: Acetazolamide 250Mg Tab

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Waterloo, Ontario, Canada, N2L3G1
      • University of Waterloo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Methazolamide; Drug: Methazolamide Dose: 100 mg b.i.d Duration: 2 days prior to testing + 1 hr prior to testing start Form: Oral	Drug: Methazolamide Pill; Oral Methazolamide
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	Drug: Acetazolamide 250Mg Tab; Oral acetazolamide
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	Drug: Placebo; Oral placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to complete a 5 km time trial after each experimental day (Days 3-5)	Primary endpoint is the time to complete a 5 km exercise task in the three arms of the trial (acetazolamide, methazolamide, placebo)	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Expired Minute Ventilation	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	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
Oxyhemoglobin saturation	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	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

Collaborators and Investigators

• Sponsor: University of Waterloo
• Collaborators: Wilderness Medical Society

Study record dates

Study Major Dates

• Study Start (Actual): August 11, 2023
• Primary Completion (Actual): February 22, 2024
• Study Completion (Actual): February 22, 2024

Study Registration Dates

• First Submitted: September 8, 2022
• First Submitted That Met QC Criteria: October 7, 2022
• First Posted (Actual): October 12, 2022

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 8, 2024
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: exercise
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Altitude Sickness; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Carbonic Anhydrase Inhibitors; Natriuretic Agents; Diuretics; Anticonvulsants; Acetazolamide; Methazolamide
• Other Study ID Numbers: 43720

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No