The Influence of Cerebral Blood Flow and PETCO2 on Neuromuscular Function During Passive Heat Stress
Primary Purpose
Healthy Males, Neuromuscular Function
Status
Completed
Phase
Phase 4
Locations
Canada
Study Type
Interventional
Intervention
Indomethacin
Placebo
Sponsored by
About this trial
This is an interventional basic science trial for Healthy Males
Eligibility Criteria
Inclusion Criteria:
- 18 to 45 yrs old; healthy males
Exclusion Criteria:
- diagnosed medical condition; NSAID allergy; smoker; high altitude exposure; implants
Sites / Locations
- Brock University
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Drug
Placebo
Arm Description
Indomethacin, 1.2 mg kg 1 dose
generic flour placebo capsule
Outcomes
Primary Outcome Measures
Resting motor threshold
Motor evoked potentials are recorded from muscles following transcranial magnetic stimulation of motor cortex. The resting motor threshold is defined as the minimum stimulation intensity required to elicit a motor evoked potential. Resting motor threshold will be quantified in millivolts.
H-Reflex Amplitude
The H-Reflex is an indirect measure of motor neuron excitability. Initially, a maximal M-wave (M-max) will be elicited by stimulating (1 ms in duration; 15 s between stimuli) the median nerve incrementally (2 V increments) until the largest waveform is observed. The peak-to-peak amplitude of this waveform is considered M-max. Using similar procedures as above, a sub-maximal M-wave of 5% M-max will be elicited and the amplitude of the resultant H-reflex (a small waveform observed following the submaximal M-wave) will be calculated. The amplitude of the H-reflex will be quantified in millivolts.
Maximal Voluntary Contraction
During maximal voluntary contraction (MVC) testing, the participants' right arm will be secured in a custom made device used to isolate forearm flexion and to measure force production by the flexor carpi radialis muscle. Participants will be asked to produce a 5-second MVC and will be verbally encouraged to maintain maximal force production throughout the duration of the contraction. MVC will be quantified as the maximum force production in newton meters.
H-Reflex latency
The H-Reflex is an indirect measure of motor neuron excitability. Initially, a maximal M-wave (M-max) will be elicited by stimulating (1 ms in duration; 15 s between stimuli) the median nerve incrementally (2 V increments) until the largest waveform is observed. The peak-to-peak amplitude of this waveform is considered M-max. Using similar procedures as above, a sub-maximal M-wave of 5% M-max will be elicited and the amplitude of the resultant H-reflex (a small waveform observed following the submaximal M-wave) will be calculated. The onset latency of the H-reflex will be quantified in milliseconds.
Voluntary Activation
The level of neural drive to muscle during contraction is termed voluntary activation and will be estimated by interpolation of a single supramaximal motor evoked potential during the 5-second MVC contraction. If extra force is evoked by the 'superimposed' stimulus then either the stimulated axons were not all recruited voluntarily or they were discharging at sub-tetanic rates. Therefore, voluntary activation will be quantified as the amplitude of maximal voluntary force production, relative to the amplitude of the supramaximal MEP.
Secondary Outcome Measures
Middle Cerebral Artery Blood Flow Velocity
Middle cerebral artery (MCA) blood flow velocity will be measured non-invasively by a 2-MHz transcranial Doppler (TCD) ultrasound probe, attached bilaterally to a comfortable headband and secured anterior to the zygomatic arch, rostral of the pinna. Doppler probes will be paced over the temporal windows (near the ear) and will remain in place throughout the duration of the experimental protocol. MCA velocity will be quantified in cm/s.
Blood Pressure
Beat by beat blood pressure will be calculated from the blood pressure waveform using finger photoplethysmography (Nexfin, bmeye), with a finger cuff placed directly over the middle finger on the left hand. Blood pressure will be quantified in mmHg.
Heart rate
Heart rate will be measured by electrocardiogram. Heart rate will be quantified in beats per minute.
End-tidal Gas concentrations
The end-tidal concentrations of oxygen and carbon dioxide will be measured and reported in mmHg.
Rectal Temperature
Rectal temperature will be measured in degrees Celsius
Skin Temperature
skin temperature will be measured in degrees Celsius
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01848665
Brief Title
The Influence of Cerebral Blood Flow and PETCO2 on Neuromuscular Function During Passive Heat Stress
Official Title
The Influence of Cerebral Blood Flow and PETCO2 on Neuromuscular Function During Passive Heat Stress
Study Type
Interventional
2. Study Status
Record Verification Date
January 2018
Overall Recruitment Status
Completed
Study Start Date
May 2013 (undefined)
Primary Completion Date
June 2015 (Actual)
Study Completion Date
December 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Brock University
4. Oversight
5. Study Description
Brief Summary
Increased core temperature (hyperthermia) has been associated with impaired neuromuscular performance; however, the mechanisms associated with these performance decrements and their potential synergies remain unclear. While the majority of research suggests that the observed fatigue is related to the central nervous system, the influence of changes in cerebral blood flow (CBF) and associated changes in cerebral alkalosis (estimated by end-tidal partial pressure of carbon dioxide; PETCO2) remains unexamined. In response to hyperthermia, humans hyperventilate as means of heat dissipation, resulting in a hypocapnia (reduced PETCO2) mediated decrease in CBF and consequently, cerebral alkalosis (increased cerebral pH). Previous research suggests that hyperventilation induces changes in neural excitability and synaptic transmission; however, it remains unclear if these changes are related to hypocapnia mediated decrease in CBF or decreased PETCO2 or both.
The purpose of the proposed research program is to examine the influence of changes in CBF and cerebral alkalosis on neuromuscular function during passive heat stress. The research project will consist of 3 separate experimental trials: (a) poikilocapnic hyperthermia (increased core temperature; decrease CBF; decrease PETCO2), (b) isocapnic hyperthermia (increased core temperature; no change CBF; no change PETCO2) and (c) isocapnic hyperthermia + indomethacin (increased core temperature; decrease CBF; no change PETCO2). During each manipulation, neuromuscular function will be evaluated and compared to baseline (normothermic) conditions using a repeated measures design.
It is hypothesized that changes in PETCO2 and therefore, changes in cerebral alkalosis will contribute to neuromuscular fatigue independent of changes in CBF or increases in core temperature.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Healthy Males, Neuromuscular Function
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
Participant
Allocation
Randomized
Enrollment
8 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Drug
Arm Type
Experimental
Arm Description
Indomethacin, 1.2 mg kg 1 dose
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
generic flour placebo capsule
Intervention Type
Drug
Intervention Name(s)
Indomethacin
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Resting motor threshold
Description
Motor evoked potentials are recorded from muscles following transcranial magnetic stimulation of motor cortex. The resting motor threshold is defined as the minimum stimulation intensity required to elicit a motor evoked potential. Resting motor threshold will be quantified in millivolts.
Time Frame
Change from baseline 90-minutes
Title
H-Reflex Amplitude
Description
The H-Reflex is an indirect measure of motor neuron excitability. Initially, a maximal M-wave (M-max) will be elicited by stimulating (1 ms in duration; 15 s between stimuli) the median nerve incrementally (2 V increments) until the largest waveform is observed. The peak-to-peak amplitude of this waveform is considered M-max. Using similar procedures as above, a sub-maximal M-wave of 5% M-max will be elicited and the amplitude of the resultant H-reflex (a small waveform observed following the submaximal M-wave) will be calculated. The amplitude of the H-reflex will be quantified in millivolts.
Time Frame
Change from baseline 90-minutes
Title
Maximal Voluntary Contraction
Description
During maximal voluntary contraction (MVC) testing, the participants' right arm will be secured in a custom made device used to isolate forearm flexion and to measure force production by the flexor carpi radialis muscle. Participants will be asked to produce a 5-second MVC and will be verbally encouraged to maintain maximal force production throughout the duration of the contraction. MVC will be quantified as the maximum force production in newton meters.
Time Frame
Change from baseline 90-minutes
Title
H-Reflex latency
Description
The H-Reflex is an indirect measure of motor neuron excitability. Initially, a maximal M-wave (M-max) will be elicited by stimulating (1 ms in duration; 15 s between stimuli) the median nerve incrementally (2 V increments) until the largest waveform is observed. The peak-to-peak amplitude of this waveform is considered M-max. Using similar procedures as above, a sub-maximal M-wave of 5% M-max will be elicited and the amplitude of the resultant H-reflex (a small waveform observed following the submaximal M-wave) will be calculated. The onset latency of the H-reflex will be quantified in milliseconds.
Time Frame
Change from baseline 90-minutes
Title
Voluntary Activation
Description
The level of neural drive to muscle during contraction is termed voluntary activation and will be estimated by interpolation of a single supramaximal motor evoked potential during the 5-second MVC contraction. If extra force is evoked by the 'superimposed' stimulus then either the stimulated axons were not all recruited voluntarily or they were discharging at sub-tetanic rates. Therefore, voluntary activation will be quantified as the amplitude of maximal voluntary force production, relative to the amplitude of the supramaximal MEP.
Time Frame
change from baseline 90-minutes
Secondary Outcome Measure Information:
Title
Middle Cerebral Artery Blood Flow Velocity
Description
Middle cerebral artery (MCA) blood flow velocity will be measured non-invasively by a 2-MHz transcranial Doppler (TCD) ultrasound probe, attached bilaterally to a comfortable headband and secured anterior to the zygomatic arch, rostral of the pinna. Doppler probes will be paced over the temporal windows (near the ear) and will remain in place throughout the duration of the experimental protocol. MCA velocity will be quantified in cm/s.
Time Frame
Change from baseline 90-minutes
Title
Blood Pressure
Description
Beat by beat blood pressure will be calculated from the blood pressure waveform using finger photoplethysmography (Nexfin, bmeye), with a finger cuff placed directly over the middle finger on the left hand. Blood pressure will be quantified in mmHg.
Time Frame
Change from baseline 90-minutes
Title
Heart rate
Description
Heart rate will be measured by electrocardiogram. Heart rate will be quantified in beats per minute.
Time Frame
Change from baseline 90-minutes
Title
End-tidal Gas concentrations
Description
The end-tidal concentrations of oxygen and carbon dioxide will be measured and reported in mmHg.
Time Frame
change from baseline 90-minutes
Title
Rectal Temperature
Description
Rectal temperature will be measured in degrees Celsius
Time Frame
change from baseline 90-minutes
Title
Skin Temperature
Description
skin temperature will be measured in degrees Celsius
Time Frame
change from baseline 90-minutes
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
18 to 45 yrs old; healthy males
Exclusion Criteria:
diagnosed medical condition; NSAID allergy; smoker; high altitude exposure; implants
Facility Information:
Facility Name
Brock University
City
St Catharines
State/Province
Ontario
ZIP/Postal Code
L2S 3A1
Country
Canada
12. IPD Sharing Statement
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The Influence of Cerebral Blood Flow and PETCO2 on Neuromuscular Function During Passive Heat Stress
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