Motor Asymmetry in Progressive Multiple Sclerosis Patients

Multiple Sclerosis, Secondary Progressive Clinical Trial

— MAP-MS  

Official title:

Motor Asymmetry in Progressive Multiple Sclerosis Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04918225
• Other study ID #: 35RC20_9751_MAP-MS
• Status: Recruiting
• Start date: November 3, 2021
• Est. completion date: May 2026

Study information

• Verified date: April 2023
• Source: Rennes University Hospital
• Contact: Anne Kerbrat, MD
• Phone: +33(0)299287076
• Email: anne.kerbrat[@]chu-rennes.fr
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: May 2026
• Est. primary completion date: May 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Chronic Progressive
• Multiple Sclerosis, Primary Progressive
• Multiple Sclerosis, Secondary Progressive
• Sclerosis

Intervention

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
• 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
• 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

Locations

Country	Name	City	State
France	Hôpital de la Timone, AP-HM	Marseille
France	CHU de Rennes - Hôpital Pontchaillou	Rennes

Sponsors (1)

Lead Sponsor	Collaborator
Rennes University Hospital

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Link between the asymmetry of functional motor impairment and the asymmetry of structural damage on the motor pathways	To study the link between the asymmetry of functional motor impairment and the asymmetry of structural damage on the motor pathways (intra-patient assessment).	Baseline
Secondary	prognostic value of motor tract focal and diffuse damage on clinical scores variations	To study the prognostic value of motor tract focal and diffuse damage on clinical scores variations at 2 years	24 months
Secondary	link between fatigability, fatigue and analytical disorders	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)	24 months
Secondary	link between fatigue and fatigability and the focal and diffuse impairment of the motor pathways	To study the link between fatigue and fatigability and the focal and diffuse impairment of the motor pathways.	24 months