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Motor Asymmetry in Progressive Multiple Sclerosis Patients (MAP-MS)

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ClinicalTrials.gov Identifier: NCT04918225
Recruitment Status : Recruiting
First Posted : June 8, 2021
Last Update Posted : January 31, 2022
Sponsor:
Information provided by (Responsible Party):
Rennes University Hospital

Brief Summary:

Project Rational

A better understanding of the causes of physical disability is an important unmet need in progressive Multiple Sclerosis patients. Progressive Multiple Sclerosis patients most often present a worsening pyramidal syndrome of lower and, to a lesser extent, upper limbs (Lublin et al., 2014) suggesting a strong corticospinal tract involvement. The systematic high resolution Magnetic Resonance Imaging exploration of lesions location and severity, as well as extra-lesional tissue, on pan-medullar and encephalic motor tracts offers the opportunity to better understand the pathological mechanism associated with motor impairment.

Scientific aims

This project will follow a twofold approach. First, the investigators will consider an "inter-patient" approach where independent and absolute Magnetic Resonance metrics for each limb will be related to disability. Second, the investigators will consider an "intra-patient" approach (i.e. comparing differences of Magnetic Resonance metric and of clinical score from the left and the right side in the same patient). For this purpose, progressive Multiple Sclerosis patients with asymmetric motor impairment will be studied. Confronting clinical and Magnetic Resonance Imaging metric value asymmetries indeed offers the unique opportunity to free oneself from many confounding factors such as genetics, age, duration of disease evolution, acquisition bias, etc. These two approaches will allow us to precisely study the impact of local factors such as Multiple Sclerosis lesions located on motor tracts on motor disability.

Methodology

The investigators propose an observational multicenter cross-sectional and prognostic study. This study will involve two French centers (Rennes, Marseille) and will include a total of 40 progressive Multiple Sclerosis patients with an asymmetrical motor deficit. Twenty sex and age matched controls will be needed to calibrate quantitative Magnetic Resonance imaging (magnetization transfer ratio). Encephalic and pan medullar structural and quantitative Magnetic Resonance images will be acquired at inclusion and clinical follow-up examinations will be performed at inclusion and 24 months. Detailed motor evaluation "per limb" will be performed, including the motor American Society Injury. Association sub-score and upper and lower limbs muscle strength measurements using a dynamometer.


Condition or disease Intervention/treatment
Multiple Sclerosis, Primary Progressive Multiple Sclerosis, Secondary Progressive Radiation: Magnetic Resonance Imaging Diagnostic Test: Neurological examination Diagnostic Test: Multiple Sclerosis Functional Composite Diagnostic Test: Physiotherapist examination

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Study Type : Observational [Patient Registry]
Estimated Enrollment : 60 participants
Observational Model: Case-Control
Time Perspective: Prospective
Target Follow-Up Duration: 24 Months
Official Title: Motor Asymmetry in Progressive Multiple Sclerosis Patients
Actual Study Start Date : November 3, 2021
Estimated Primary Completion Date : December 2024
Estimated Study Completion Date : December 2024


Group/Cohort Intervention/treatment
Progressive Multiple Sclerosis patients
Progressive Multiple Sclerosis patients
Radiation: Magnetic Resonance Imaging

Encephalic (about 30 minutes*)

  • lesion location assessment: 3D FLAIR, 3DT1, 3DT2 (standard OFSEP protocol)
  • lesion severity assessment: Axial magnetization transfer imaging (mt0, mt1)
  • tract location assessment: 30 directions diffusion imaging (standard OFSEP protocol)
  • B0 and B1 mapping to correct for B0 and B1 inhomogeneities

    ● Spinal cord (about 50 minutes*)

  • lesion location assessment: cervical and thoracic sagittal T2 TSE (0.7x0.7x2.5mm3), axial cervical MEDIC T2* (0.7x0.7x3mm3), axial thoracic T2 (0.5x0.5x3mm3)
  • lesion severity assessment: Axial magnetization transfer imaging (mt0, mt1, 0.7x0.7x3mm3) on the cervical cord and on the thoracic cord
  • tract location assessment: performed from registration on atlas
  • B0 and B1 mapping to correct for B0 and B1 inhomogeneities

Diagnostic Test: Neurological examination
Global disability will be scored using the Expanded Disability Status Scale score

Diagnostic Test: Multiple Sclerosis Functional Composite
  • Walking disability will be scored using the 25-foot timed-walked test
  • Arm disability will be scored using the nine-hole peg test

Diagnostic Test: Physiotherapist examination
  • American Society Injury. Association motor subscore for each limb
  • The muscle strength using a dynamometer. Two muscle groups will be tested for the upper (elbow flexors and extensors) and lower limbs (hip flexors and ankle dorsiflexion).
  • The Ashworth Scale and the Tardieu Scale to assess spasticity.
  • 6 minutes walking test
  • Fatigue Severity Scale
  • MFIS : Modified Fatigue Impact Scale

Healthy Volunteers
Healthy Volunteers
Radiation: Magnetic Resonance Imaging

Encephalic (about 30 minutes*)

  • lesion location assessment: 3D FLAIR, 3DT1, 3DT2 (standard OFSEP protocol)
  • lesion severity assessment: Axial magnetization transfer imaging (mt0, mt1)
  • tract location assessment: 30 directions diffusion imaging (standard OFSEP protocol)
  • B0 and B1 mapping to correct for B0 and B1 inhomogeneities

    ● Spinal cord (about 50 minutes*)

  • lesion location assessment: cervical and thoracic sagittal T2 TSE (0.7x0.7x2.5mm3), axial cervical MEDIC T2* (0.7x0.7x3mm3), axial thoracic T2 (0.5x0.5x3mm3)
  • lesion severity assessment: Axial magnetization transfer imaging (mt0, mt1, 0.7x0.7x3mm3) on the cervical cord and on the thoracic cord
  • tract location assessment: performed from registration on atlas
  • B0 and B1 mapping to correct for B0 and B1 inhomogeneities




Primary Outcome Measures :
  1. link between focal and diffuse damage in motor tract [ Time Frame: Baseline ]
    link between focal and diffuse damage in motor tract per side and it functional consequences per limb assessed clinically at baseline


Secondary Outcome Measures :
  1. Link between the asymmetry of functional motor impairment and the asymmetry of structural damage on the motor pathways [ Time Frame: Baseline ]
    To study the link between the asymmetry of functional motor impairment and the asymmetry of structural damage on the motor pathways (intra-patient assessment).

  2. prognostic value of motor tract focal and diffuse damage on clinical scores variations [ Time Frame: 24 months ]
    To study the prognostic value of motor tract focal and diffuse damage on clinical scores variations at 2 years

  3. link between fatigability, fatigue and analytical disorders [ Time Frame: 24 months ]
    To explore fatigability during the 6-minute instrumented walking test (evolution of spatio-temporal parameters: walking speed, step length, cadence; feeling of fatigue) and to study the link between fatigability, fatigue and analytical disorders (strength, spasticity)

  4. link between fatigue and fatigability and the focal and diffuse impairment of the motor pathways [ Time Frame: 24 months ]
    To study the link between fatigue and fatigability and the focal and diffuse impairment of the motor pathways.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Patient population will consist of progressive Multiple Sclerosis patients (both Primary Progressive Multiple Sclerosis and Secondary Progressive Multiple Sclerosis), a population for whom a better understanding of the causes of disability is an unmet need.
Criteria
  1. - Inclusion Criteria:

    1.1/ Patients:

    • Aged between 18 and 60 years.
    • Primary Progressive Multiple Sclerosis or Secondary Progressive Multiple Sclerosis as defined by Mac Donald revised criteria in 2017.
    • Expanded Disability Status Scale lower or equal to 8.0, at inclusion.
    • asymmetric motor deficit. The motor deficit asymmetry will be defined by a difference of 3 or more at the American Society Injury. Association motor sub-score per limb between the right lower limb and the left lower limb.
    • No evidence of focal inflammatory activity for at least 3 years (no clinical relapse, no gadolinium enhancement on an Magnetic Resonance Imaging scan and no new T2 lesion)
    • Provided written informed consent according to the Institutional review board approval
    • Affiliated to the French healthcare system.

    1.2 / Controls:

    • Aged between 18 and 60 years, sex and age matched with patients.
    • Provided written informed consent according to the Institutional review board approval
    • Affiliated to the French healthcare system.
  2. - Non-inclusion criteria:

2.1 /Patients:

  • cerebellar Expanded Disability Status Scale sub score higher than pyramidal Expanded Disability Status Scale sub score.
  • Relapse or corticosteroids in the 30 days preceding inclusion.
  • Other neurological diseases.
  • Lack of ability to understand the Institutional review board consent form.
  • Magnetic Resonance contraindications.
  • Pregnancy and breastfeeding.
  • Major persons subject to legal protection (legal safeguards, guardianship,curatorship), persons deprived of their liberty

2.2 / Controls:

  • Personal history of central nervous related disease
  • Familial history of Multiple Sclerosis.
  • Personal history of spinal cord injury.
  • Personal history of spondylotic myelopathy.
  • Magnetic Resonance Imaging contraindication.
  • Lack of ability to understand the Institutional review board form.
  • Major persons subject to legal protection (legal safeguards, guardianship, curatorship), persons deprived of their liberty
  • Pregnancy and breastfeeding.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04918225


Contacts
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Contact: Anne Kerbrat, MD +33(0)299287076 anne.kerbrat@chu-rennes.fr

Locations
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France
Hôpital de la Timone, AP-HM Not yet recruiting
Marseille, France, 13385
Contact: Bertrand Audoin, MD    +33(0)4 91 38 59 39    bertrand.audoin@ap-hm.fr   
Principal Investigator: Bertrand Audoin, MD         
CHU de Rennes - Hôpital Pontchaillou Recruiting
Rennes, France, 35033
Contact: Anne Kerbrat, MD    +33(0)299287076    anne.kerbrat@chu-rennes.fr   
Principal Investigator: Anne Kerbrat, MD         
Sponsors and Collaborators
Rennes University Hospital
Investigators
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Principal Investigator: Anne Kerbrat, MD CHU Rennes
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Responsible Party: Rennes University Hospital
ClinicalTrials.gov Identifier: NCT04918225    
Other Study ID Numbers: 35RC20_9751_MAP-MS
First Posted: June 8, 2021    Key Record Dates
Last Update Posted: January 31, 2022
Last Verified: January 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Rennes University Hospital:
motor disability, Magnetic Resonance Imaging
Additional relevant MeSH terms:
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Multiple Sclerosis
Multiple Sclerosis, Chronic Progressive
Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases