Muscle Fatigue and Carbonic Anhydrase Inhibitors

Overview

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.

Full Title of Study: “The Effect of Carbonic Anhydrase Inhibitors on the Pulmonary System Response to Muscle Fatigue.”

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: June 30, 2017

Interventions

• Drug: Acetazolamide
  • 250 mg, taken orally three times per day
• Drug: Methazolamide
  • 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.
• Other: Placebo
  • A placebo will be taken three times per day

Arms, Groups and Cohorts

• Experimental: Acetazolamide
  • 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.
• Experimental: Methazolamide
  • 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.
• Placebo Comparator: Placebo
  • Participants will take three placebo pills per day for two days prior to and a single dose on the morning of the experimental day.

Clinical Trial Outcome Measures

Primary Measures

• Change in trans-diaphragmatic pressure generation to supramaximal phrenic nerve stimulation following inspiratory threshold loading.
  • Time Frame: 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
  • Time Frame: Baseline, 1, 5, 10, 20, and 30 minutes following the loading protocol for each arm of the study

Secondary Measures

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

Participating in This Clinical Trial

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.

Gender Eligibility: Male

Minimum Age: 18 Years

Maximum Age: 40 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

• Lead Sponsor
  • University of British Columbia
• Provider of Information About this Clinical Study
  • Principal Investigator: Glen Foster, Assistant Professor – University of British Columbia
• Overall Official(s)
  • Glen E Foster, Ph.D., Principal Investigator, University of British Columbia

Citations Reporting on Results

Dominelli PB, McNeil CJ, Vermeulen TD, Stuckless TJR, Brown CV, Dominelli GS, Swenson ER, Teppema LJ, Foster GE. Effect of acetazolamide and methazolamide on diaphragm and dorsiflexor fatigue: a randomized controlled trial. J Appl Physiol (1985). 2018 Sep 1;125(3):770-779. doi: 10.1152/japplphysiol.00256.2018. Epub 2018 May 24.