Multiple SclerosisNCT02623946
Motor Evoked Potentials as a Biomarker in Alemtuzumab Treated Multiple Sclerosis Patients
An observational study of Multiple Sclerosis, run by Clinique Neuro-Outaouais at 1 site in Canada.
Trial summary
Study Design: Phase 4, pilot, single center, observational study. MEP's will be obtained twice, two weeks apart at baseline and every 6 months for 36 months (total of 14 sessions of MEP's) MEP's will include: 1. Onset latencies and CMCT to bilateral abductor pollicis brevis and tibialis anterior muscles 2. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Sclerosis
- How many people
- 10 participants
- Where
- 1 siteCanada
- Study dates
- Nov 2015to Feb 2021
- Phase
- Observational
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with MacDonald criteria (2005) multiple sclerosis presently being treated with Alemtuzumab.
Who may be able to join
- Diagnosis of MS (McDonald criteria) and of age 18 and older;
- Subjects who meet the prescribing criteria for Alemtuzumab as per product monograph;
- An EDSS of 5.0 or less and a pyramidal system functional assessment score of 2 or greater;
- Subject who have received the first cycle of Alemtuzumab within the last 3 months.
Who cannot join
- Subjects who have begun using extended release Fampridine within 2 months of study baseline visit (Patient on a stable dose of extended release Fampridine for more than 2 months can enter the study);
- Subjects with MSSS (Multiple Sclerosis Severity Score) less than 4.0;
- Subject with other medical conditions that involve the CST's;
- Any other condition that would preclude them from undergoing the MEP's and/or MRI.
Trial locations and contacts
1 site in 1 country.
About this study
Study Design:
Phase 4, pilot, single center, observational study. MEP's will be obtained twice, two weeks apart at baseline and every 6 months for 36 months (total of 14 sessions of MEP's)
Read more
MEP's will include:
- Onset latencies and CMCT to bilateral abductor pollicis brevis and tibialis anterior muscles
- MEP amplitudes and the ratio of the central to peripherally obtained motor amplitudes (MEP-M ratio) to bilateral abductor pollicis brevis and tibialis anterior muscles Clinical measures (EDSS, MEP's, T25FWT, 6MWT, 9HPT) will be obtained at baseline and every 6 months for 36 months.
Study location: Single center in Canada
Study Objectives:
Primary: To evaluate the reliability of MEP's in Alemtuzumab treated MS patients over a 36 month period.
Secondary: To determine the degree of correlation between MEP's and presently used clinical measures of efficacy (EDSS, 6MWT, T25FWT, 9HPT) and to determine if MEP's can predict who will require a third cycle of Alemtuzumab.
Read the detailed description
Alemtuzumab pivotal studies have shown robust effect on relapse rate and MRI parametric. The effect on disease progression did not however reach statistical significance in CARE MS I Clinical trials, especially in the progressive forms of Multiple Sclerosis (MS) have been greatly hampered by the insensitivity of the Expanded Disability Status Scale (EDSS) especially at either ends of the scale. Other more recently introduced clinical scales such the timed 25 foot walk test (T25FWT), six minute walk test (6MWT) or the 9-hole peg test (9HPT) also lack in sensitivity and reliability. A validated, sensitive and reliable biomarker for disability progression or regression would greatly help clinical research in MS. Such a biomarker could also help in evaluating if and when patients would require retreatments with Alemtuzumab.
Motor evoked potentials (MEP's) measures the integrity and function of corticospinal tracts. The procedure uses an electromagnet to induce directly or via interneurons a small depolarizing current in the axon hillock of large pyramidal neurons in the motor cortex. A subsequent motor response can then be measured in the targeted limb muscle. The amplitude and latency of such response can be measured giving an indication of the conduction integrity of the corticospinal tracts (CST) from the cortex to the limb. MEP's are able to detect perhaps even before clinical measures, evidence of CST involvement and deterioration through increased central motor conduction time and/or reduced ratio of centrally elicited MEP amplitude to peripherally elicited compound motor amplitude potential (CMAP).
MEP's have been studied in a variety of pathologies involving CST's. MEP's have in patients with cervical spondylosis as well as with patients with amyotrophic lateral sclerosis, shown to being more sensitive than clinical examination in detecting CST involvement. MEP's have been shown in MS to correlate with EDSS scores. In studies looking at spinal cord injury patients MEP's were able to demonstrate an improvement in central motor conduction time (CMCT) induced by extended release fampridine.
The main critique of MEP's has been as in all electrophysiological tests one of high intra-patient variability which can be compounded by non-standardized techniques between centers. Newer MEP techniques using neuro-navigation, standardized facilitation techniques and choosing the best of three responses can significantly reduce the inherent variability of obtained values. We believe that with such techniques MEP's can become a useful surrogate biomarker in clinical trials of MS. The latter however needs to be validated in a prospective manner.
- Conditions
- Multiple Sclerosis
- Keywords
- motor evoked potentials
- Medical subject headings
- Multiple Sclerosis
What is being measured
The primary outcome is the main question the study is designed to answer.
intrapatient correlation coefficient of MEP's
to measure within subject correlation a two-way fixed Intraclass Correlation (ICC) will be calculated for each of 10 participants across sessions measured two weeks apart. The ICC will provide an estimate of the variance of each individual's motor evoked potentials at each paired time point.
Measured: obtained between two assessments done two weeks apart
Secondary outcomes (2)
Correlation coefficient between the changes from baseline MEP results and clinical measures (EDSS, 6MW, T25FWT, 9HPT)
to measure the relationship between MEP change scores and the change scores of the clinical measures, several correlations will be run across 6 months intervals over the 36 month period. The corrrelation between the individual changes in MEP results and the propensity to require a third cycle of alemtuzumab will also be calcutlated.
Measured: obtained every 6 months for 36 months
Correlation between the change in the conduction index and the change in clincal measures
to measure the correlation betwen the conduction index results and the clinical measures and the change in the conduction index over time and the change in the clinical measures over the 36month period.
Measured: obtained at baseline and every 6 months over 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Dec 2015 (estimated)
- Study startNov 2015
- Primary completion9 Dec 2020
- Study completionFeb 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Clinique Neuro-Outaouais
- Sponsor type
- University, hospital or other
- Collaborators
- CogState Ltd.
- Responsible party
- Principal investigator, Dr. Francois Jacques, Clinique Neuro-Outaouais
- Investigators
- Francois H Jacques, MD, Principal investigator, Clinic Neuro-Outaouais; Director
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02623946
- Sponsor's protocol ID
- CNO-004
- Status last verified
- Jul 2020
- First submitted
- 30 Nov 2015
- Last updated
- 28 Jul 2021
- Results posted
- No
- Data monitoring committee
- No
Publications
Jacques FH, Apedaile BE, Danis I, Sikati-Foko V, Lecompte M, Fortin J. Motor Evoked Potential-A Pilot Study Looking at Reliability and Clinical Correlations in Multiple Sclerosis. J Clin Neurophysiol. 2024 May 1;41(4):357-364. doi: 10.1097/WNP.0000000000001003. Epub 2023 Mar 21.
PubMed 36943437
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Motor Evoked Potentials as a Biomarker in Alemtuzumab Treated Multiple Sclerosis Patients
- ClinicalTrials.gov ID
- NCT02623946
- Acronym / sponsor ID
- CNO-004
- Conditions
- Multiple Sclerosis
- Keywords
- motor evoked potentials
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Clinique Neuro-OutaouaisUniversity, hospital or other
- Collaborators
- CogState Ltd.
- Study start
- Nov 2015 (actual)
- Primary completion
- 9 Dec 2020 (actual)
- Study completion
- Feb 2021 (actual)
- First posted
- 8 Dec 2015 (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:
Phase 4, pilot, single center, observational study. MEP's will be obtained twice, two weeks apart at baseline and every 6 months for 36 months (total of 14 sessions of MEP's)
MEP's will include:
- Onset latencies and CMCT to bilateral abductor pollicis brevis and tibialis anterior muscles
- MEP amplitudes and the ratio of the central to peripherally obtained motor amplitudes (MEP-M ratio) to bilateral abductor pollicis brevis and tibialis anterior muscles Clinical measures (EDSS, MEP's, T25FWT, 6MWT, 9HPT) will be obtained at baseline and every 6 months for 36 months.
Study location: Single center in Canada
Study Objectives:
Primary: To evaluate the reliability of MEP's in Alemtuzumab treated MS patients over a 36 month period.
Secondary: To determine the degree of correlation between MEP's and presently used clinical measures of efficacy (EDSS, 6MWT, T25FWT, 9HPT) and to determine if MEP's can predict who will require a third cycle of Alemtuzumab.
Detailed description
Alemtuzumab pivotal studies have shown robust effect on relapse rate and MRI parametric. The effect on disease progression did not however reach statistical significance in CARE MS I Clinical trials, especially in the progressive forms of Multiple Sclerosis (MS) have been greatly hampered by the insensitivity of the Expanded Disability Status Scale (EDSS) especially at either ends of the scale. Other more recently introduced clinical scales such the timed 25 foot walk test (T25FWT), six minute walk test (6MWT) or the 9-hole peg test (9HPT) also lack in sensitivity and reliability. A validated, sensitive and reliable biomarker for disability progression or regression would greatly help clinical research in MS. Such a biomarker could also help in evaluating if and when patients would require retreatments with Alemtuzumab.
Motor evoked potentials (MEP's) measures the integrity and function of corticospinal tracts. The procedure uses an electromagnet to induce directly or via interneurons a small depolarizing current in the axon hillock of large pyramidal neurons in the motor cortex. A subsequent motor response can then be measured in the targeted limb muscle. The amplitude and latency of such response can be measured giving an indication of the conduction integrity of the corticospinal tracts (CST) from the cortex to the limb. MEP's are able to detect perhaps even before clinical measures, evidence of CST involvement and deterioration through increased central motor conduction time and/or reduced ratio of centrally elicited MEP amplitude to peripherally elicited compound motor amplitude potential (CMAP).
MEP's have been studied in a variety of pathologies involving CST's. MEP's have in patients with cervical spondylosis as well as with patients with amyotrophic lateral sclerosis, shown to being more sensitive than clinical examination in detecting CST involvement. MEP's have been shown in MS to correlate with EDSS scores. In studies looking at spinal cord injury patients MEP's were able to demonstrate an improvement in central motor conduction time (CMCT) induced by extended release fampridine.
The main critique of MEP's has been as in all electrophysiological tests one of high intra-patient variability which can be compounded by non-standardized techniques between centers. Newer MEP techniques using neuro-navigation, standardized facilitation techniques and choosing the best of three responses can significantly reduce the inherent variability of obtained values. We believe that with such techniques MEP's can become a useful surrogate biomarker in clinical trials of MS. The latter however needs to be validated in a prospective manner.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with MacDonald criteria (2005) multiple sclerosis presently being treated with Alemtuzumab.
Key inclusion criteria (4 listed)
- Diagnosis of MS (McDonald criteria) and of age 18 and older;
- Subjects who meet the prescribing criteria for Alemtuzumab as per product monograph;
- An EDSS of 5.0 or less and a pyramidal system functional assessment score of 2 or greater;
- Subject who have received the first cycle of Alemtuzumab within the last 3 months.
Key exclusion criteria (4 listed)
- Subjects who have begun using extended release Fampridine within 2 months of study baseline visit (Patient on a stable dose of extended release Fampridine for more than 2 months can enter the study);
- Subjects with MSSS (Multiple Sclerosis Severity Score) less than 4.0;
- Subject with other medical conditions that involve the CST's;
- Any other condition that would preclude them from undergoing the MEP's and/or MRI.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
intrapatient correlation coefficient of MEP's
Time frame: obtained between two assessments done two weeks apart
to measure within subject correlation a two-way fixed Intraclass Correlation (ICC) will be calculated for each of 10 participants across sessions measured two weeks apart. The ICC will provide an estimate of the variance of each individual's motor evoked potentials at each paired time point.
2 secondary outcomes
Correlation coefficient between the changes from baseline MEP results and clinical measures (EDSS, 6MW, T25FWT, 9HPT)
Time frame: obtained every 6 months for 36 months
Correlation between the change in the conduction index and the change in clincal measures
Time frame: obtained at baseline and every 6 months over 36 months
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 28 Jul 2021.
- Derived from this study: PubMed 36943437Jacques FH, Apedaile BE, Danis I, Sikati-Foko V, Lecompte M, Fortin J. Motor Evoked Potential-A Pilot Study Looking at Reliability and Clinical Correlations in Multiple Sclerosis. J Clin Neurophysiol. 2024 May 1;41(4):357-364. doi: 10.1097/WNP.0000000000001003. Epub 2023 Mar 21.
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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.
Francois H Jacques, MD principal investigator
Clinic Neuro-Outaouais; Director
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Multiple Sclerosis, run by Clinique Neuro-Outaouais 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 4 inclusion and 4 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 28 Jul 2021. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
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?
intrapatient correlation coefficient of MEP's (time frame: obtained between two assessments done two weeks apart). 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 NCT02623946, which also lists 1 linked publication.
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 28 Jul 2021.