Muscle Fatigue and Carbonic Anhydrase Inhibitors

Sponsor

University of British Columbia (Other)

Overall Status

Completed

CT.gov ID

NCT02758470

Collaborator

(none)

Enrollment

Location

Arms

7.9

Duration (Months)

1.6

Patients Per Site Per Month

Study Details

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

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 :

Nov 1, 2016

Actual Primary Completion Date :

Jun 30, 2017

Actual Study Completion Date :

Jun 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

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

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

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 Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 40 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Yes

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.