Muscle Fatigue and Carbonic Anhydrase Inhibitors

NCT02758470 | Completed Phase 4

• 1 other identifier: H16-00896
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

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.

Conditions

Hypoxia

Keywords

Muscle Fatigue; Acetazolamide; Methazolamide

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• 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

Other Outcomes (3)

• Esophageal and Gastric Pressure

  Baseline, 1, 5, 10, 20, and 30 minutes post loading protocol

• Heart Rate

  Baseline, 1, 5, 10, 20, and 30 minutes post loading protocol

• Beat-by-beat blood pressure

  Baseline, 1, 5, 10, 20, and 30 minutes post loading protocol

Study Arms (3)

Acetazolamide

EXPERIMENTAL

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

Methazolamide

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Acetazolamide DRUG

250 mg, taken orally three times per day

Acetazolamide

Methazolamide DRUG

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.

Methazolamide

Placebo OTHER

A placebo will be taken three times per day

Placebo

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age: 18-40 years.
• Regularly physically active
• Male

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of British Columbia: lead

Study Sites (1)

University of British Columbia

Kelowna, British Columbia, V1V 1V7, Canada

Location

Related Publications (1)

• 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.

  PMID: 29792554 RESULT

MeSH Terms

Conditions

Hypoxia

Interventions

Acetazolamide; Methazolamide

Condition Hierarchy (Ancestors)

Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiadiazoles; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Glen E Foster, Ph.D.

  University of British Columbia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: April 20, 2016
• First Posted: May 2, 2016
• Study Start: November 1, 2016
• Primary Completion: June 30, 2017
• Study Completion: June 30, 2017
• Last Updated: September 25, 2018

Record last verified: 2018-09

Locations

CA (1)