Muscle Fatigue and Carbonic Anhydrase Inhibitors

Study Overview
=================
Brief Summary
-----------------
The objective of this research is to assess the effects of acetazolamide and methazolamide on respiratory and limb muscle fatigue development. A fatiguing protocol will be conducted for the respiratory and plantar flexor muscles and the difference in pressure/torque produced by supramaximal nerve stimulation used to assess muscle fatigue between conditions.

Official Title
-----------------
The Effect of Carbonic Anhydrase Inhibitors on the Pulmonary System Response to Muscle Fatigue.

Conditions
-----------------
Hypoxia

Intervention / Treatment
-----------------
* Drug: Acetazolamide
* Drug: Methazolamide
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age: 18-40 years. Regularly physically active Male Exclusion Criteria: current or ex-smokers pulmonary function <80% of predicted esophageal tumour or ulcer have had recent (<6 months) musculoskeletal injury or any surgery to the lower leg have contraindications to carbonic anhydrase inhibitors (eg. severe or absolute glaucoma, adrenocortical insufficiency, hepatic insufficiency, renal insufficiency, sulfa allergy or an electrolyte imbalance such as hyperchloremic acidosis) are obese (BMI >30 Kg/m2) taking diuretics, blood thinners, or anti-platelet drugs.

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

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acetazolamide<br>Participants will be dosed 250mg acetazolamide (p.o.) three times per day for two days prior to and a single dose on the morning of the experimental day. | Drug: Acetazolamide<br>* 250 mg, taken orally three times per day<br>|
| Experimental: Methazolamide<br>Participants will be dosed 100mg Methazolamide (p.o.) two times per day separated by a placebo dose for two days prior to and a single dose on the morning of the experimental day. The placebo dose is used to match the timing and number of pills taken between all arms of the study. | Drug: Methazolamide<br>* 100mg, taken orally two times per day. A placebo pill will be taken between each dose of methazolamide to match the timing of doses and the number of pills between study arms.<br>|
| Placebo Comparator: Placebo<br>Participants will take three placebo pills per day for two days prior to and a single dose on the morning of the experimental day. | Other: Placebo<br>* A placebo will be taken three times per day<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in trans-diaphragmatic pressure generation to supramaximal phrenic nerve stimulation following inspiratory threshold loading. |  | Baseline, 1, 5, 10, 20, and 30 minutes following the loading protocol for each arm of the study | 
| Change in plantar flexor muscle group torque generation to supramaximal tibial nerve stimulation following an isometric loading protocol |  | Baseline, 1, 5, 10, 20, and 30 minutes following the loading protocol for each arm of the study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximal inspiratory pressure maneuvers |  | Baseline and immediately following loading protocol | 
| Maximal Voluntary Contraction of the Plantar Flexor Muscle Group |  | Baseline and immediately following the loading protocol | 
| Contraction time and half-relaxation time |  | Baseline, 1, 5, 10, 20, and 30 minutes post loading protocol | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Muscle Fatigue, Acetazolamide, Methazolamide