Cerebral Blood Flow and PETCO2 on Neuromuscular Function During Environmental Stress

NCT01830335 | Completed Phase 4

• 1 other identifier: 12-167
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

Environmental stress, such as low oxygen availability (hypoxia), has been associated with impaired neuromuscular performance; however, the mechanisms associated with these performance decrements 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 pH (partial pressure of carbon dioxide; PCO2) remains unexamined. In response to hypoxic stress, humans hyperventilate to maintain oxygen consumption, resulting in a hypocapnia mediated decrease in CBF and cerebral alkalosis (decreased PCO2). 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 cerebral alkalosis 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 environmental stress. The research program will consist of 2 separate projects, summarized below in a table outlining the proposed protocols and resultant physiological manipulations. During each manipulation, neuromuscular function will be evaluated and compared to baseline (normoxic) conditions using a repeated measures design. The research program will consist of 2 separate projects. Project 1 will examine the changes in CBF and alkalosis by using (a) indomethacin (decrease CBF; no change PCO2) and (b) hypocapnia (decrease CBF; decrease PCO2). Using a similar experimental design, Project 2 will examine the change in CBF and alkalosis during hypoxia by using (a) poikilocapnic hypoxia (decrease PO2; decrease CBF; decrease PCO2), (b) isocapnic hypoxia (decrease PO2; no change CBF; no change PCO2) and (c) isocapnic hypoxia + indomethacin (decrease PO2; decrease CBF; no change PCO2). During each manipulation, neuromuscular function will be evaluated and compared to baseline (normoxic) conditions using a repeated measures design. Therefore, Project 1 will examine the separate and combined effect of changes in CBF and cerebral alkalosis on neuromuscular function independent of environmental manipulations. Subsequently, Project 2 will examine neuromuscular function during hypoxia while controlling CBF and cerebral alkalosis. It is hypothesized that changes in PCO2 and therefore, changes in cerebral alkalosis will contribute to neuromuscular fatigue independent of changes in CBF and oxygen availability.

Conditions

Healthy Males; Neuromuscular Function

Outcome Measures

Primary Outcomes (5)

• 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.

  Change from baseline 90-minutes

• 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 milllivolts.

  Change from baseline 90-minutes

• 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.

  Change from baseline 90-minutes

• 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.

  Change from baseline 90-minutes

• 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.

  Change from baseline 90-minutes

Secondary Outcomes (7)

• Middle Cerebral Artery Blood Flow Velocity

  Change from baseline 90-minutes

• Brachial Artery Blood flow

  Change from baseline 90-minutes

• Internal Carotid Artery Blood Flow

  Change from baseline 90-minutes

• Blood pressure

  Change from baseline 90-minutes

• Pulse oximetry

  Change from baseline 90-minutes

Study Arms (2)

Drug

EXPERIMENTAL

Indomethacin 1.2 mg kg 1 dose

Drug: Indomethacin

Placebo

PLACEBO COMPARATOR

flour capsule

Drug: Placebo

Interventions

Indomethacin DRUG

Drug

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years - 25 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• to 25 yrs old; healthy males

You may not qualify if:

• diagnosed medical condition; NSAID allergy; smoker; high altitude exposure; implants

Sponsors & Collaborators

• Brock University: lead

Study Sites (1)

Brock University

St. Catharines, Ontario, L2S 3A1, Canada

Location

MeSH Terms

Interventions

Indomethacin

Intervention Hierarchy (Ancestors)

Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Stephen Cheung, PhD

  Brock University

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: March 20, 2013
• First Posted: April 12, 2013
• Study Start: April 1, 2013
• Primary Completion: June 1, 2015
• Study Completion: December 1, 2016
• Last Updated: January 29, 2018

Record last verified: 2018-01

Locations

CA (1)