Healthy MalesPhase 4NCT01830335

Cerebral Blood Flow and PETCO2 on Neuromuscular Function During Environmental Stress

A Phase 4 study testing Indomethacin in people with Healthy Males and Neuromuscular Function, run by Brock University at 1 site in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 25 years, men onlyHealthy volunteers can take part
Conditions the study is for: Healthy Males, Neuromuscular Function
What is being tested?: Indomethacin
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 8 participants
Where: 1 siteCanada
Study dates: Apr 2013to Dec 2016
Phase: Phase 4
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 25 years
Men only
Healthy volunteers accepted
Adult

Who may be able to join

18 to 25 yrs old; healthy males

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

Canada1 site

Brock University
St. Catharines, Ontario, L2S 3A1

Other trials in Canada

About this study

Official title: The Influence of Cerebral Blood Flow and Alkalosis on Neuromuscular Function During Environmental Stress

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
Being tested: Indomethacin, Placebo

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

IndomethacinDrug
PlaceboDrug

Study groups in NCT01830335
Study group	Role	What they receive
Drug	Experimental	Indomethacin 1.2 mg kg 1 dose Receives: Drug: Indomethacin
Placebo	Placebo comparator	flour capsule Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Change from baseline 90-minutes

Secondary outcomes (7)

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.
Measured: Change from baseline 90-minutes
Brachial Artery Blood flow
Brachial artery blood flow will be measured non-invasively using a high-resolution ultrasound machine. Participants will lie supine with their forearm extended in a comfortable position. Blood flow measurements will be taken in the top 1/3 of the upper arm over the duration of 10 cardiac cycles (approximately 60 seconds). Blood flow will be quantified in L/min.
Measured: Change from baseline 90-minutes
Internal Carotid Artery Blood Flow
Internal carotid artery (ICA) blood flow will be measured non-invasively using a high-resolution ultrasound machine. Participants will lie supine with a slight extension of the neck and at 45° of lateral flexion away from the side being scanned. ICA measurements will be taken 1 cm superior to the common carotid bifurcation over the duration of 10 cardiac cycles (approximately 60 seconds). Blood flow will be quantified in L/min.
Measured: Change from baseline 90-minutes
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.
Measured: Change from baseline 90-minutes
Pulse oximetry
A pulse oximetry probe will be placed over a finger to provide a continuous, non-invasive measurement of the blood oxygen saturation to confirm that the end-tidal forcing system is controlling oxygen delivery at the desired levels during each experiment. Oxygen saturation will be quantified as a percentage.
Measured: Change from baseline 90-minutes
Heart Rate
Heart rate will be measured by electrocardiogram. Heart rate will be quantified in beats per minute.
Measured: Change from baseline 90-minutes
End-Tidal Gas Concentrations
The end-tidal concentrations of oxygen and carbon dioxide will be measured and reported in mmHg.
Measured: Change from baseline 90-minutes

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Apr 2013Dec 2016

First posted12 Apr 2013 (estimated)
Study startApr 2013
Primary completionJun 2015
Study completionDec 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Healthy MalesStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Single group
Masking: Single blind
Who is masked: Participant
Enrolment: 8 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01830335
Sponsor's protocol ID: 12-167
Status last verified: Jan 2018
First submitted: 20 Mar 2013
Last updated: 29 Jan 2018
Results posted: No
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 29 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: The Influence of Cerebral Blood Flow and Alkalosis on Neuromuscular Function During Environmental Stress
ClinicalTrials.gov ID: NCT01830335
Acronym / sponsor ID: 12-167
Conditions: Healthy Males, Neuromuscular Function
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 8 participants (actual)
Lead sponsor: Brock UniversityUniversity, hospital or other
Study start: Apr 2013
Primary completion: Jun 2015 (actual)
Study completion: Dec 2016 (actual)
First posted: 12 Apr 2013 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Single group
Masking: Single blind (participant)
Number of arms: 2

Arm	Type	Receives
Drug	Experimental	Drug: IndomethacinIndomethacin 1.2 mg kg 1 dose
Placebo	Placebo comparator	Drug: Placeboflour capsule

Who may qualify

Ages: 18 to 25 years
Sex: Male only
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (1 listed)

18 to 25 yrs old; healthy males

Key exclusion criteria (1 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Indomethacin	Drug	Drug
Placebo	Drug	Placebo

Primary outcome

Resting motor threshold
Time frame: Change from baseline 90-minutes
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
Time frame: Change from baseline 90-minutes
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.
Maximal Voluntary Contraction
Time frame: Change from baseline 90-minutes
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
Time frame: Change from baseline 90-minutes
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
Time frame: Change from baseline 90-minutes
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.

7 secondary outcomes

Middle Cerebral Artery Blood Flow Velocity
Time frame: Change from baseline 90-minutes
Brachial Artery Blood flow
Time frame: Change from baseline 90-minutes
Internal Carotid Artery Blood Flow
Time frame: Change from baseline 90-minutes
Blood pressure
Time frame: Change from baseline 90-minutes
Pulse oximetry
Time frame: Change from baseline 90-minutes
Heart Rate
Time frame: Change from baseline 90-minutes
End-Tidal Gas Concentrations
Time frame: Change from baseline 90-minutes

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 29 Jan 2018.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Stephen Cheung, PhD principal investigator

Brock University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Indomethacin in people with Healthy Males and Neuromuscular Function, run by Brock University at 1 site in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Resting motor threshold (time frame: Change from baseline 90-minutes). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01830335.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jan 2018.