Clinical trial NCT05622643: OFSEP Very High Definition Cohort
Official title: Very High Definition Cohort: Assessment of New Prognostic Biomarkers of Disability Worsening in a Multicenter Cohort of MS Patients by Imaging, Optical Coherence Tomography and Biology
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Multiple Sclerosis
Keywords: Prognostic factors
MS progression
MRI
OCT
NFL
GFAP
Lead sponsor: EDMUS Foundation
Sponsor class: OTHER
First posted: 2022-11-18
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: In order to ensure the inclusion of patients with different MS phenotypes representative of the general MS patients population in the VHD cohort, the investigators will aim to respect the inclusion percentages of at least 10% of patients with primary progressive MS and at least 15% of patients with secondary progressive MS.

Brief summary: Multiple sclerosis (MS) is the most common acquired neurological disease leading to disability in young adults. MS often leads to the development of a physical and/or cognitive impairment that disables patients in their daily lives. Early use of disease modifying treatments for patients at risk of developing disability is therefore essential.

However, disability progression is very heterogeneous between patients and currently impossible to predict at the individual level. Thus, numerous studies, particularly epidemiological and imaging studies, have identified prognostic factors for the development of disability such as age, gender, number of relapses during the first years of the disease, existence of a residual disability after a first relapse, number of gadolinium-enhancing lesions on initial MRI, early brainstem and spinal cord lesions. However, these different factors only explain incompletely the progression of the physical or cognitive disability in MS patients. In particular, some components of MS pathophysiology, more related to the progressive development of disability, such as axonal degeneration or the existence of chronic inflammation of the central nervous system (CNS) are usually not measured by these biomarkers.

In this research project, the investigators will test promising biomarkers, focused on these components of the disease, on a large cohort of patients in a multicenter setting, in order to evaluate their added value to predict disability progression, in comparison with more classical biomarkers such as clinical characteristics, and brain and spinal cord lesion load.

In particular, the investigators will test:

* Imaging biomarkers extracted from brain and spinal cord MP2RAGE, brain and spinal cord QSM, brain and spinal cord relaxometry, brain diffusion and spinal cord magnetization transfer sequences
* Biomarkers extracted from optical coherence tomography (OCT)
* Biological biomarkers (serum neurofilament-light chain (NFL) and Glial Fibrillary Acidic Protein (GFAP))


Eligibility criteria: For MS patients:

* Inclusion Criteria:

  * The patient must be already included in the OFSEP High Definition cohort (NCT03603457).
  * The patient must have given his informed and signed consent for the inclusion in the VHD cohort.
  * The patient must be insured or beneficiary of a health insurance plan.
* Exclusion Criteria:

  * The patient is under judicial protection.
  * The patient refuses to sign the consent.
  * It is impossible to correctly inform the patient (Inability to understand the study, language problem).
  * The patient has experienced a relapse in the previous 3 months.
  * The patient is pregnant or breast-feeding (MRI contraindicated).
  * Patient with MRI contra-indications (patient with a pacemaker, ferromagnetic vascular clip, infusion pump, neurostimulator, cochlear implants or in whom there is a suspicion of a metallic foreign body).
  * The patient has a severe psychiatric illness
  * The patient has severe chronic alcoholism

For healthy subjects:

* Inclusion Criteria:

  * The healthy subject must be older than 18 years
  * The healthy subject must have given his informed and signed consent for the inclusion in the VHD cohort.
  * The healthy subject must be insured or beneficiary of a health insurance plan.
* Exclusion Criteria:

  * The healthy subject is under judicial protection.
  * It is impossible to correctly inform the healthy subject (Inability to understand the study, language problem).
  * The healthy subject is pregnant or breast-feeding (MRI contraindicated).
  * The healthy subject has MRI contra-indications (a pacemaker, ferromagnetic vascular clip, infusion pump, neurostimulator, cochlear implants or in whom there is a suspicion of a metallic foreign body).
  * The healthy subject has a history of disease that may affect the central nervous system.
  * The healthy subject has a family history of MS.

Primary outcomes:
measure: Global disability progression
timeFrame: 2 years
Secondary outcomes:
measure: Composite disability progression score
timeFrame: 2 years
measure: Change in the Symbol Digit Modalities Test score
timeFrame: 2 years
measure: Change in the American Spinal Cord Injury Association motor sub-score
timeFrame: 2 years
measure: Focal inflammatory activity
timeFrame: 2 years
measure: No evidence of disease activity 3
timeFrame: 2 years
measure: Between-subject, between-center and between-session coefficient of variation of measurements extracted quantitative MRI
timeFrame: At inclusion
measure: Number of brain and spinal cord lesion detected using 3D MP2RAGE sequence and the classical OFSEP sequences at baseline and 2 year
timeFrame: At inclusion and 2 years
measure: Number of new brain and spinal cord lesion detected at 2 years using 3DMP2RAGE sequence and the classical OFSEP sequences
timeFrame: 2 years
measure: Number of detected brain and spinal cord lesions per patient and per expert with and without the automatic tool at baseline and 2 year
timeFrame: At baseline and 2 year
Other outcomes:
Locations:
city: Lyon
country: France
facility: CHU de Lyon
city: Nancy
country: France
facility: CHU de Nancy
city: Nîmes
country: France
facility: CHU de Nîmes
city: Rennes
country: France
facility: CHU de Rennes
city: Strasbourg
country: France
facility: CHU de Strasbourg
Study officials:
References: