Muscle Fatigue and Carbonic Anhydrase Inhibitors

• ClinicalTrials.gov Identifier: NCT02758470
• Recruitment Status: Completed
• First Posted: May 2, 2016
• Last Update Posted: September 25, 2018
• Sponsor: University of British Columbia
• Information provided by (Responsible Party): Glen Foster, University of British Columbia

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Hypoxia	Drug: Acetazolamide; Drug: Methazolamide; Other: Placebo	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 13 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Basic Science
• Official Title: The Effect of Carbonic Anhydrase Inhibitors on the Pulmonary System Response to Muscle Fatigue.
• Study Start Date: November 2016
• Actual Primary Completion Date: June 30, 2017
• Actual Study Completion Date: June 30, 2017

Arms and Interventions

Arm	Intervention/treatment
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.	Drug: Acetazolamide; 250 mg, taken orally three times per 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.	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.
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.	Other: Placebo; A placebo will be taken three times per day

Outcome Measures

Primary Outcome Measures :

1. 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 ]
2. 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 Outcome Measures :

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

Other Outcome Measures:

1. Esophageal and Gastric Pressure [ Time Frame: Baseline, 1, 5, 10, 20, and 30 minutes post loading protocol ]
2. Heart Rate [ Time Frame: Baseline, 1, 5, 10, 20, and 30 minutes post loading protocol ]
3. Beat-by-beat blood pressure [ Time Frame: Baseline, 1, 5, 10, 20, and 30 minutes post loading protocol ]

Eligibility Criteria

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

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.

Contacts and Locations

Locations

Canada, British Columbia

University of British Columbia

Kelowna, British Columbia, Canada, V1V 1V7

Sponsors and Collaborators

University of British Columbia

Investigators

• Principal Investigator: Glen E Foster, Ph.D.; University of British Columbia

More Information

Publications of 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.

• Responsible Party: Glen Foster, Assistant Professor, University of British Columbia
• ClinicalTrials.gov Identifier: NCT02758470
• Other Study ID Numbers: H16-00896
• First Posted: May 2, 2016
• Last Update Posted: September 25, 2018
• Last Verified: September 2018

Keywords provided by Glen Foster, University of British Columbia:

Muscle Fatigue; Acetazolamide; Methazolamide

Additional relevant MeSH terms:

Fatigue; Hypoxia; Signs and Symptoms, Respiratory; Acetazolamide; Methazolamide; Anticonvulsants; Carbonic Anhydrase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Diuretics; Natriuretic Agents; Physiological Effects of Drugs