Motor Asymmetry in Progressive Multiple Sclerosis Patients

NCT04918225 | Completed

• 1 other identifier: 35RC20_9751_MAP-MS
• Study Type: observational
• Target: 46
• Locations: 1 country
• Sites: 1

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.

Conditions

Multiple Sclerosis, Primary Progressive; Multiple Sclerosis, Secondary Progressive

Keywords

motor disability, Magnetic Resonance Imaging

Outcome Measures

Primary Outcomes (1)

• link between focal and diffuse damage in motor tract

  link between focal and diffuse damage in motor tract per side and it functional consequences per limb assessed clinically at baseline

  Baseline

Secondary Outcomes (4)

• Link between the asymmetry of functional motor impairment and the asymmetry of structural damage on the motor pathways

  Baseline

• prognostic value of motor tract focal and diffuse damage on clinical scores variations

  24 months

• link between fatigability, fatigue and analytical disorders

  24 months

• link between fatigue and fatigability and the focal and diffuse impairment of the motor pathways

  24 months

Study Arms (2)

Progressive Multiple Sclerosis patients

Progressive Multiple Sclerosis patients

Radiation: Magnetic Resonance Imaging; Diagnostic Test: Neurological examination; Diagnostic Test: Multiple Sclerosis Functional Composite; Diagnostic Test: Physiotherapist examination

Healthy Volunteers

Healthy Volunteers

Radiation: Magnetic Resonance Imaging

Interventions

Magnetic Resonance Imaging RADIATION

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

Healthy Volunteers; Progressive Multiple Sclerosis patients

Neurological examination DIAGNOSTIC_TEST

Global disability will be scored using the Expanded Disability Status Scale score

Progressive Multiple Sclerosis patients

Multiple Sclerosis Functional Composite DIAGNOSTIC_TEST

* Walking disability will be scored using the 25-foot timed-walked test * Arm disability will be scored using the nine-hole peg test

Progressive Multiple Sclerosis patients

Physiotherapist examination DIAGNOSTIC_TEST

* 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

Progressive Multiple Sclerosis patients

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• 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.

You may qualify if:

• / 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.
• 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.
• / 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.
• /Patients:
• cerebellar Expanded Disability Status Scale sub score higher than pyramidal Expanded Disability Status Scale sub score.
• Other neurological diseases.
• Lack of ability to understand the Institutional review board consent form.

Sponsors & Collaborators

• Rennes University Hospital: lead

Study Sites (1)

CHU de Rennes - Hôpital Pontchaillou

Rennes, 35033, France

Location

MeSH Terms

Conditions

Multiple Sclerosis, Chronic Progressive

Interventions

Magnetic Resonance Spectroscopy; Neurologic Examination

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques; Diagnostic Techniques, Neurological; Diagnostic Techniques and Procedures; Diagnosis; Physical Examination

Study Officials

• Anne Kerbrat, MD

  CHU Rennes

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Target Duration: 24 Months
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2021
• First Posted: June 8, 2021
• Study Start: November 3, 2021
• Primary Completion: February 10, 2026
• Study Completion: February 10, 2026
• Last Updated: March 19, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)