Motor Asymmetry in Progressive Multiple Sclerosis Patients

Plain English Summary

Motor Asymmetry in Progressive Multiple Sclerosis Patients is a Not Applicable clinical trial sponsored by Rennes University Hospital studying Multiple Sclerosis, Primary Progressive, Multiple Sclerosis, Secondary Progressive. This study investigates how differences in motor function between the left and right sides of the body relate to brain and spinal cord changes in people with progressive Multiple Sclerosis (MS). It is for individuals diagnosed with primary or secondary progressive MS who experience uneven weakness or difficulty using their limbs. Participation involves undergoing detailed neurological and physical examinations, as well as specialized MRI scans of the brain and spinal cord. Currently, there are no direct treatment alternatives being tested in this observational study; it aims to improve understanding of the disease. The trial aims to enroll 46 participants.

Official 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)

Who Can Participate

Here is what you need to know about eligibility for this trial. Individuals aged 18-60 with primary or secondary progressive MS. Patients must have a noticeable difference in motor function between their right and left limbs. Individuals with no signs of active MS inflammation for at least 3 years are eligible. People with other neurological conditions, or those who are pregnant or breastfeeding, are not eligible. This trial is studying Multiple Sclerosis, Primary Progressive, Multiple Sclerosis, Secondary Progressive, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures will help researchers understand how specific damage in the brain and spinal cord's motor pathways is directly linked to the physical limitations experienced by patients. The specific primary outcome measures are: link between focal and diffuse damage in motor tract (Baseline). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This study does not have a traditional clinical phase designation. It may be an observational study that follows patients without intervening in their care, an expanded access or compassionate use program, or other non-interventional research. These studies contribute valuable data about disease progression, treatment patterns, and patient outcomes.

Why This Trial Matters

This trial is important because it seeks to uncover the underlying causes of physical disability in progressive MS, addressing a significant unmet need for better understanding and future treatments. This research targets Multiple Sclerosis, Primary Progressive, Multiple Sclerosis, Secondary Progressive, where improved treatment options are needed.

Investor Insight

This observational study focuses on understanding disease mechanisms rather than developing a new therapy, making its direct investment signal limited, but it could inform future therapeutic targets f

Is This Trial Right for Me?

Ask your doctor if your specific type of MS and level of disability make you a good candidate for this type of research. Be prepared for detailed neurological tests and potentially lengthy MRI sessions. Understand that this study observes existing conditions and does not offer a new treatment. The trial is being conducted at 1 site. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: OBSERVATIONAL
• Enrollment: 46 participants

Interventions

• 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)
• 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

Primary Outcomes

• link between focal and diffuse damage in motor tract (Baseline)

Secondary Outcomes

• 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)

Full Eligibility 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.

Trial Locations

• CHU de Rennes - Hôpital Pontchaillou, Rennes, France

Frequently Asked Questions

Related Conditions

• Multiple Sclerosis, Primary Progressive
• Multiple Sclerosis, Secondary Progressive
• Neurological Disorders
• Motor Impairment
• Spinal Cord Diseases
• Brain Diseases
• Neurodegenerative Diseases
• Autoimmune Diseases
• Central Nervous System Diseases
• Disability

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