Clinical trial NCT05962177: Montpellier PROspective Cohort in Relapsing Remitting Multiple Sclerosis Using Imaging and Serologic
Official title: Montpellier PROspective Cohort in Relapsing Remitting Multiple Sclerosis Using Imaging and Serologic
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Multiple Sclerosis
Keywords: Multiple sclerosis
MRI
Longitudinal cohort
Real life
Biomarkers
Lead sponsor: University Hospital, Montpellier
Sponsor class: OTHER
First posted: 2023-07-27
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: Several prospective monocentric cohorts of between 250 and 1000 patients have been set up in order to characterize more precisely the evolution of the disease. Nevertheless, due to an initial recruitment carried out in the years 2000-2010, they do not constitute a faithful representation of the patients followed in clinical routine, in particular in terms of distribution of treatments. Indeed, the introduction, about 10 years ago, of high efficacy treatments (HET) has changed the management of the disease and a significant proportion of patients not controlled by medium efficacy treatments (MET) of the disease are now stable on HET. Nevertheless, if their short-term efficacy has been clearly demonstrated, it remains important to be able to confirm the superiority of HET over MET with the help of prospective cohorts (thus ensuring a retention of patients \> 90% over the long term) analyzing all clinical and imaging biomarkers, imaging and biological data.

The measurement of cerebral atrophy and its progression is probably one of the most interesting and most easily used biomarkers that can be used clinically to assess this silent progression in these groups of patients.

The progression of brain atrophy is also dependent on many other non-modifiable but also modifiable factors outside of MS that need to be better evaluated and eventually managed.

Nevertheless, the existence of various neurological comorbidities (sleep disorders, headaches) on this atrophy has not been specifically analyzed to date. The functional assessments used in routine follow-up are most often performed in a care facility and have many limitations: lack of reproducibility, inter/intra operator variability, poor correlation with functional and quality of life scales, etc.

It is therefore extremely important to be able to identify new clinical biomarkers of disease progression of the disease by evaluating the physical capacities of the patients as precisely as possible.

This study is a single-center, prospective cohort study of a population of 400 patients with relapsing remitting MS (RRMS).

The main objective of this study is to compare, on morphological imaging criteria (T1 volumetry), the progression of brain atrophy (biomarker of disease progression) at 3 years in RRMS patients according to treatment line (MET vs HET).

Detailed description: Several prospective monocentric cohorts of between 250 and 1000 patients have been set up in order to characterize more precisely the evolution of the disease. Nevertheless, due to an initial recruitment carried out in the years 2000-2010, they do not constitute a faithful representation of the patients followed in clinical routine, in particular in terms of distribution of treatments. Indeed, the introduction, about 10 years ago, of high efficacy treatments (HET : Natalizumab, Fingolimod, Ocrelizumab, Rituximab, Ofatumumab, Cladribine) has changed the management of the disease and a significant proportion of patients not controlled by medium efficacy treatments (MET : Beta interferons, glatiramer acetate, teriflunomide, dimethyl fumarate, monomethyl fumarate) of the disease are now stable on HET. Nevertheless, if their short-term efficacy has been clearly demonstrated, it remains important to be able to confirm the superiority of HET over MET with the help of prospective cohorts (thus ensuring a retention of patients \> 90% over the long term) analyzing all clinical and imaging biomarkers, imaging and biological data.

The measurement of cerebral atrophy and its progression is probably one of the most interesting and most easily used biomarkers that can be used clinically to assess this silent progression in these groups of patients.

The progression of brain atrophy is also dependent on many other non-modifiable but also modifiable factors outside of MS that need to be better evaluated and eventually managed.

Nevertheless, the existence of various neurological comorbidities (sleep disorders, headaches) on this atrophy has not been specifically analyzed to date. The functional assessments used in routine follow-up are most often performed in a care facility and have many limitations: lack of reproducibility, inter/intra operator variability, poor correlation with functional and quality of life scales, etc.

It is therefore extremely important to be able to identify new clinical biomarkers of disease progression of the disease by evaluating the physical capacities of the patients as precisely as possible.

This study is a single-center, prospective cohort study of a population of 400 patients with relapsing remitting MS (RRMS).

The main objective of this study is to compare, on morphological imaging criteria (T1 volumetry), the progression of brain atrophy (biomarker of disease progression) at 3 years in RRMS patients according to treatment line (MET vs HET).

3 groups of interest will be studied and included in the study:

* Group 1: RRMS with medium efficacy treatment (interferon beta, glatiramer acetate, Teriflunomide, dimethyl fumarate, monomethyl fumarate) of the disease (n=175 patients)
* Group 2: RRMS with high efficacy treatment (Natalizumab, Ocrelizumab, Rituximab, Ofatumumab, Fingolimod, Cladribine: n=175 patients)
* Group 3: Untreated RRMS (n=50 patients)

Eligibility criteria: Inclusion Criteria:

* Patients over 18 and under 55 years of age
* Patients with Relapsing-remitting MS without relapse for at least 6 months
* EDSS\<6 at time of inclusion

Exclusion Criteria:

* Secondary progressive MS or Primary progressive MS at time of inclusion
* Evidence of disease progression (clinical or radiological)
* Change in treatment in the year prior to inclusion
* Subject with a contraindication to MRI (claustrophobia, pacemaker, etc.)
* Inability to follow the follow-up planned by the study
* Pregnant or breastfeeding women
* Patient not affiliated to the social security system or not benefiting from such a system
* Adult protected by law or patient under guardianship or curatorship
* Failure to obtain written informed consent after a reflection period

Primary outcomes:
measure: Total brain atrophy
timeFrame: 3 years after Day 1
Secondary outcomes:
measure: Quantitative analysis: analysis of FLAIR hypersignals number
timeFrame: 3 years after Day 1
measure: Quantitative analysis: analysis of FLAIR hypersignals volume
timeFrame: 3 years after Day 1
measure: Qualitative analysis: analysis of central vein lesions
timeFrame: 3 years after Day 1
measure: Qualitative analysis: analysis of peripheral rim lesion
timeFrame: 3 years after Day 1
measure: Quantitative analysis: measurement of mean diffusivity
timeFrame: 3 years after Day 1
measure: Quantitative analysis: measurement of anisotropy fraction
timeFrame: 3 years after Day 1
measure: Quantitative analysis: measurement of cerebral blood flow (CBF)
timeFrame: 3 years after Day 1
measure: Changes in serum light chain neurofilament values
timeFrame: 3 years after Day 1
measure: Clinical assessment scale: relapses
timeFrame: 3 years after Day 1
measure: Clinical assessment scale: Expanded Disability Status Scale (EDSS)
timeFrame: 3 years after Day 1
measure: Clinical assessment scale: Computerized Speed Cognitive Test (CSCT)
timeFrame: 3 years after Day 1
measure: Clinical assessment scale: Six-Minute Walk Test (6MWT)
timeFrame: 3 years after Day 1
measure: Clinical assessment scale: 9-Hole Peg Test (9-HPT)
timeFrame: 3 years after Day 1
measure: Clinical assessment scale: Timed 25-Foot Walk (T25-FW)
timeFrame: 3 years after Day 1
measure: Quality of life scale: The 5-level EQ-5D questionnaire (EQ5D-5L)
timeFrame: 3 years after Day 1
measure: Quality of life scale: The Brief Pain Inventory (BPI)
timeFrame: 3 years after Day 1
measure: Quality of life scale: DN4
timeFrame: 3 years after Day 1
measure: Fatigue scale: Chalder Fatigue Scale
timeFrame: 3 years after Day 1
measure: Fatigue scale: Modified Fatigue Impact Scale (MFIS)
timeFrame: 3 years after Day 1
measure: Sleep scale: Epworth Sleepiness Scale (ESS)
timeFrame: 3 years after Day 1
measure: Depression scale: Beck Depression Inventory (BID)
timeFrame: 3 years after Day 1
measure: Anxiety scale: Generalized Anxiety Disorder 7-Item Scale (GAD-7)
timeFrame: 3 years after Day 1
measure: Headaches scale: ef-ID Migraine
timeFrame: 3 years after Day 1
measure: Exploratory criteria:Serum Glial Fibrillary Acidic Protein (GFAP)
timeFrame: 3 years after Day 1
measure: Exploratory criteria: Pittsburgh Sleep Quality Index (PSQI) questionnaire
timeFrame: 3 years after Day 1
measure: Exploratory criteria: Idiopathic Hypersomnia Severity Hypersomnia Scale (IHSS)
timeFrame: 3 years after Day 1
measure: Exploratory criteria: RU SATED score
timeFrame: 3 years after Day 1
measure: Exploratory criteria: Insomnia Severity Index (ISI)
timeFrame: 3 years after Day 1
measure: Exploratory criteria: Headaches Impact Test (HIT-6)
timeFrame: 3 years after Day 1
measure: Exploratory criteria: Godin Leisure-Time Exercise Questionnaire (GLTEQ)
timeFrame: 3 years after Day 1
Other outcomes:
Locations:
city: Montpellier
country: France
facility: Neurology Department, Hopital Gui de Chauliac
Study officials:
References: