Assessment of NfL and GFAP Levels, Atrophy of the Macula GCC by OCT and Whole Brain Atrophy by MRI to Predict Evolution of Neurological Disability in MS Patients

Study Overview
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Brief Summary
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The investigators hypothesize that serum neurofilament-light chain (NfL) levels at baseline and decrease of the macular ganglion cell complex (GCC) thickness at one year vs. baseline are as good as progression of whole brain atrophy at one year vs. baseline to predict later evolution of neurological disability in multiple sclerosis patients.

Official Title
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Assessment of Serum Neurofilament-light Chain (NfL) and Glial Fibrillary Acidic Protein (GFAP) Levels, Atrophy of the Macular Ganglion Cell Complex (GCC) by Optical Coherence Tomography (OCT) and Whole Brain Atrophy by MRI to Predict Evolution of Neurological Disability in Multiple Sclerosis Patients

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Diagnostic Test: Brain MRI
* Diagnostic Test: Spinal Cord MRI
* Diagnostic Test: Retinal imaging


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient has been correctly informed. The patient must have given their informed and signed consent. The patient must be insured or beneficiary of a health insurance plan. The patient is at least (≥)18 years old. The patient has experienced a CIS, has currently a RRMS or progressive MS with: Less than 10 years of disease duration; With or without DMD; EDSS score 0 - 7.0. Exclusion Criteria: The patient is in an exclusion period determined by a previous study. 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 is pregnant or breast-feeding. Patient has a bilateral optic neuritis or other significant ophthalmological antecedent. Patient with MRI contra-indications. patient has a contraindication to gadolinium injection The patient has bilateral optic neuritis or other significant ophthalmological antecedent Patient is having a relapse or has had a relapse in the last 3 months The patient has a severe psychiatric illness The patient has severe chronic alcoholism

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| MS patients<br> | Diagnostic Test: Brain MRI<br>* Axial DWI with ADC card Axial 2D TSE T2/DP or 3DT2 Gadolinium injection (0.1 mmol/kg) 3D Fluid-attenuated inversion recovery 3D T1 with Gadolinium injection.<br>Diagnostic Test: Spinal Cord MRI<br>* Sagittal T2 Sagittal T1 with Gadolinium injection<br>Diagnostic Test: Retinal imaging<br>* spectral-domain high definition optical coherence tomography<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in serum Neurofilament Light Chain serum levels since baseline | pg/mL; measured by digital ELISA | Baseline; 1 year | 
| Change in serum Glial Fibrillary Acidic Protein (GFAP) serum levels since baseline | pg/mL; measured by digital ELISA | Baseline; 1 year | 
| Change in Ganglion Cell Complex thickness since baseline | Measured by Optical Coherence Tomography | Baseline; 1 year | 
| Change in whole brain volume since baseline | Assessed by MRI | Baseline; 1 year | 
| Expanded Disability Status Scale | Eight functional systems scored on a scale of 0 (no disability) to 5 or 6 (more severe disability) | Baseline | 
| Expanded Disability Status Scale | Eight functional systems scored on a scale of 0 (no disability) to 5 or 6 (more severe disability) | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Whole brain volume | assessed by MRI | Inclusion | 
| Whole brain volume | assessed by MRI | 6 Months | 
| Whole brain volume | assessed by MRI | 1 Year | 
| Whole brain volume | assessed by MRI | 2 years | 
| Whole brain volume | assessed by MRI | 3 Years | 
| Whole brain volume | assessed by MRI | 4 Years | 
| Whole brain volume | assessed by MRI | 5 years | 
| Whole brain volume | assessed by MRI | any relapse (max 5 years) | 
| Expanded Disability Status Scale | Eight functional systems scored on a scale of 0 (no disability) to 5 or 6 (more severe disability) | Inclusion | 
| Expanded Disability Status Scale | Eight functional systems scored on a scale of 0 (no disability) to 5 or 6 (more severe disability) | 6 Months | 
| Expanded Disability Status Scale | Eight functional systems scored on a scale of 0 (no disability) to 5 or 6 (more severe disability) | 1 year | 
| Expanded Disability Status Scale | Eight functional systems scored on a scale of 0 (no disability) to 5 or 6 (more severe disability) | 18 months | 
| Expanded Disability Status Scale | Eight functional systems scored on a scale of 0 (no disability) to 5 or 6 (more severe disability) | 2 years | 
| Expanded Disability Status Scale | Eight functional systems scored on a scale of 0 (no disability) to 5 or 6 (more severe disability) | 2.5 years | 
| Expanded Disability Status Scale | Eight functional systems scored on a scale of 0 (no disability) to 5 or 6 (more severe disability) | 3 years | 
| Expanded Disability Status Scale | Eight functional systems scored on a scale of 0 (no disability) to 5 or 6 (more severe disability) | 3.5 years | 
| Expanded Disability Status Scale | Eight functional systems scored on a scale of 0 (no disability) to 5 or 6 (more severe disability) | 4 years | 
| Expanded Disability Status Scale | Eight functional systems scored on a scale of 0 (no disability) to 5 or 6 (more severe disability) | 4.5 years | 
| Expanded Disability Status Scale | Eight functional systems scored on a scale of 0 (no disability) to 5 or 6 (more severe disability) | 5 years | 
| Expanded Disability Status Scale | Eight functional systems scored on a scale of 0 (no disability) to 5 or 6 (more severe disability) | Any relapse (Maximum 5 years) | 
| Peripapillary Retinal Nerve Fibre Layer atrophy and Ganglion Cell Complex thickness | assessed by Optical Coherence Tomography | Inclusion | 
| Peripapillary Retinal Nerve Fibre Layer atrophy and Ganglion Cell Complex thickness | assessed by Optical Coherence Tomography | 6 Months | 
| Peripapillary Retinal Nerve Fibre Layer atrophy and Ganglion Cell Complex thickness | assessed by Optical Coherence Tomography | 1 Year | 
| Peripapillary Retinal Nerve Fibre Layer atrophy and Ganglion Cell Complex thickness | assessed by Optical Coherence Tomography | 18 Months | 
| Peripapillary Retinal Nerve Fibre Layer atrophy and Ganglion Cell Complex thickness | assessed by Optical Coherence Tomography | 2 years | 
| Peripapillary Retinal Nerve Fibre Layer atrophy and Ganglion Cell Complex thickness | assessed by Optical Coherence Tomography | 3 Years | 
| Peripapillary Retinal Nerve Fibre Layer atrophy and Ganglion Cell Complex thickness | assessed by Optical Coherence Tomography | 4 Years | 
| Peripapillary Retinal Nerve Fibre Layer atrophy and Ganglion Cell Complex thickness | assessed by Optical Coherence Tomography | 5 Years | 
| Peripapillary Retinal Nerve Fibre Layer atrophy and Ganglion Cell Complex thickness | assessed by Optical Coherence Tomography | Any relapse (maximum 5 Years) | 
| Gadolinium-enhanced lesions | assessed by MRI | Inclusion | 
| Gadolinium-enhanced lesions | assessed by MRI | 6 Months | 
| Gadolinium-enhanced lesions | assessed by MRI | 1 Year | 
| Gadolinium-enhanced lesions | assessed by MRI | 2 years | 
| Gadolinium-enhanced lesions | assessed by MRI | 3 Years | 
| Gadolinium-enhanced lesions | assessed by MRI | 4 Years | 
| Gadolinium-enhanced lesions | assessed by MRI | 5 Years | 
| Gadolinium-enhanced lesions | assessed by MRI | Any relapse (Maximum 5 Years) | 
| T2 lesion volume, | assessed by MRI | Inclusion | 
| T2 lesion volume, | assessed by MRI | 6 Months | 
| T2 lesion volume, | assessed by MRI | 1 Year | 
| T2 lesion volume, | assessed by MRI | 2 years | 
| T2 lesion volume, | assessed by MRI | 3 Years | 
| T2 lesion volume, | assessed by MRI | 4 Years | 
| T2 lesion volume, | assessed by MRI | 5 years | 
| T2 lesion volume, | assessed by MRI | Any relapse (maximum 5 years) | 
| Grey matter atrophy | assessed by MRI | Inclusion | 
| Grey matter atrophy | assessed by MRI | 6 Months | 
| Grey matter atrophy | assessed by MRI | 1 Year | 
| Grey matter atrophy | assessed by MRI | 2 years | 
| Grey matter atrophy | assessed by MRI | 3 Years | 
| Grey matter atrophy | assessed by MRI | 4 Years | 
| Grey matter atrophy | assessed by MRI | 5 Years | 
| Grey matter atrophy | assessed by MRI | Any relapse (maximum 5 Years) | 
| White matter atrophy | assessed by MRI | Inclusion | 
| White matter atrophy | assessed by MRI | 6 Months | 
| White matter atrophy | assessed by MRI | 1 Year | 
| White matter atrophy | assessed by MRI | 2 years | 
| White matter atrophy | assessed by MRI | 3 Years | 
| White matter atrophy | assessed by MRI | 4 Years | 
| White matter atrophy | assessed by MRI | 5 years | 
| White matter atrophy | assessed by MRI | Any relapse (maximum 5 years) | 
| Thalamic atrophy | assessed by MRI | Inclusion | 
| Thalamic atrophy | assessed by MRI | 6 Months | 
| Thalamic atrophy | assessed by MRI | 1 Year | 
| Thalamic atrophy | assessed by MRI | 2 years | 
| Thalamic atrophy | assessed by MRI | 3 Years | 
| Thalamic atrophy | assessed by MRI | 4 Years | 
| Thalamic atrophy | assessed by MRI | 5 years | 
| Thalamic atrophy | assessed by MRI | Any relapse (maximum 5 years) | 
| Disease modifying drugs classification | Drug class (1st, 2nd or 3rd line) | Inclusion | 
| Disease modifying drugs classification | Drug class (1st, 2nd or 3rd line) | until end of study (5 years) | 
| serum NfL levels | pg/mL; measured by digital ELISA | 6 Months | 
| serum GFAP levels | pg/mL; measured by digital ELISA | 6 Months | 
| serum NfL levels | pg/mL; measured by digital ELISA | 2 years | 
| serum GFAP levels | pg/mL; measured by digital ELISA | 2 years | 
| serum NfL levels | pg/mL; measured by digital ELISA | 3 years | 
| serum GFAP levels | pg/mL; measured by digital ELISA | 3 years | 
| serum NfL levels | pg/mL; measured by digital ELISA | 4 years | 
| serum GFAP levels | pg/mL; measured by digital ELISA | 4 years | 
| serum NfL levels | pg/mL; measured by digital ELISA | 5 years | 
| serum GFAP levels | pg/mL; measured by digital ELISA | 5 years | 
| serum NfL levels | pg/mL; measured by digital ELISA | Any relapse (maximum 5 years) | 
| serum GFAP levels | pg/mL; measured by digital ELISA | Any relapse (maximum 5 years) | 
| Multiple Sclerosis Functional Composite | 21-item test that includes 3 different functional subtests: the timed 25-Foot Walk, the 9-Hole Peg Test and the Paced Auditory Serial Addition Test (PASAT) | Inclusion | 
| Multiple Sclerosis Functional Composite | 21-item test that includes 3 different functional subtests: the timed 25-Foot Walk, the 9-Hole Peg Test and the Paced Auditory Serial Addition Test (PASAT) | 6 Months | 
| Multiple Sclerosis Functional Composite | 21-item test that includes 3 different functional subtests: the timed 25-Foot Walk, the 9-Hole Peg Test and the Paced Auditory Serial Addition Test (PASAT) | 1 Year | 
| Multiple Sclerosis Functional Composite | 21-item test that includes 3 different functional subtests: the timed 25-Foot Walk, the 9-Hole Peg Test and the Paced Auditory Serial Addition Test (PASAT) | 2 years | 
| Multiple Sclerosis Functional Composite | 21-item test that includes 3 different functional subtests: the timed 25-Foot Walk, the 9-Hole Peg Test and the Paced Auditory Serial Addition Test (PASAT) | 3 years | 
| Multiple Sclerosis Functional Composite | 21-item test that includes 3 different functional subtests: the timed 25-Foot Walk, the 9-Hole Peg Test and the Paced Auditory Serial Addition Test (PASAT) | 4 years | 
| Multiple Sclerosis Functional Composite | 21-item test that includes 3 different functional subtests: the timed 25-Foot Walk, the 9-Hole Peg Test and the Paced Auditory Serial Addition Test (PASAT) | 5 years | 
| Multiple Sclerosis Functional Composite | 21-item test that includes 3 different functional subtests: the timed 25-Foot Walk, the 9-Hole Peg Test and the Paced Auditory Serial Addition Test (PASAT) | Any relapse (maximum 5 years) | 
| Time to walk 100 meters | Seconds | Inclusion | 
| Time to walk 100 meters | Seconds | 6 Months | 
| Time to walk 100 meters | Seconds | 1 Year | 
| Time to walk 100 meters | Seconds | 2 years | 
| Time to walk 100 meters | Seconds | 3 years | 
| Time to walk 100 meters | Seconds | 4 years | 
| Time to walk 100 meters | Seconds | 5 years | 
| Time to walk 100 meters | Seconds | Any relapse (maximum 5 years) | 
| 2 Minute walking distance | Meters | Inclusion | 
| 2 Minute walking distance | Meters | 6 Months | 
| 2 Minute walking distance | Meters | 1 Year | 
| 2 Minute walking distance | Meters | 2 years | 
| 2 Minute walking distance | Meters | 3 years | 
| 2 Minute walking distance | Meters | 4 years | 
| 2 Minute walking distance | Meters | 5 years | 
| 2 Minute walking distance | Meters | Any relapse (maximum 5 years) | 
| Cognitive Impairment | Symbol Digit Modalities Test | Inclusion | 
| Cognitive Impairment | Symbol Digit Modalities Test | 6 months | 
| Cognitive Impairment | Symbol Digit Modalities Test | 1 Year | 
| Cognitive Impairment | Symbol Digit Modalities Test | 2 years | 
| Cognitive Impairment | Symbol Digit Modalities Test | 3 years | 
| Cognitive Impairment | Symbol Digit Modalities Test | 4 years | 
| Cognitive Impairment | Symbol Digit Modalities Test | 5 years | 
| Cognitive Impairment | Symbol Digit Modalities Test | Any relapse (maximum 5 years) | 
| Cognitive evaluation | Brief International Cognitive Assessment for Multiple Sclerosis | Inclusion | 
| Cognitive evaluation | Brief International Cognitive Assessment for Multiple Sclerosis | 6 Months | 
| Cognitive evaluation | Brief International Cognitive Assessment for Multiple Sclerosis | 1 Year | 
| Cognitive evaluation | Brief International Cognitive Assessment for Multiple Sclerosis | 2 years | 
| Cognitive evaluation | Brief International Cognitive Assessment for Multiple Sclerosis | 3 years | 
| Cognitive evaluation | Brief International Cognitive Assessment for Multiple Sclerosis | 4 years | 
| Cognitive evaluation | Brief International Cognitive Assessment for Multiple Sclerosis | 5 years | 
| Cognitive evaluation | Brief International Cognitive Assessment for Multiple Sclerosis | Any relapse (maximum 5 years) | 
| Health-related quality of life | EQ-5D-5L | Inclusion | 
| Health-related quality of life | EQ-5D-5L | 6 Months | 
| Health-related quality of life | EQ-5D-5L | 1 Year | 
| Health-related quality of life | EQ-5D-5L | 2 years | 
| Health-related quality of life | EQ-5D-5L | 3 years | 
| Health-related quality of life | EQ-5D-5L | 4 years | 
| Health-related quality of life | EQ-5D-5L | 5 years | 
| Health-related quality of life | EQ-5D-5L | Any relapse (maximum 5 years) | 
| Impact of MS on daily life | Multiple Sclerosis Impact Scale (MSIS-29) | Inclusion | 
| Impact of MS on daily life | Multiple Sclerosis Impact Scale (MSIS-29) | 6 Months | 
| Impact of MS on daily life | Multiple Sclerosis Impact Scale (MSIS-29) | 1 Year | 
| Impact of MS on daily life | Multiple Sclerosis Impact Scale (MSIS-29) | 2 years | 
| Impact of MS on daily life | Multiple Sclerosis Impact Scale (MSIS-29) | 3 years | 
| Impact of MS on daily life | Multiple Sclerosis Impact Scale (MSIS-29) | 4 years | 
| Impact of MS on daily life | Multiple Sclerosis Impact Scale (MSIS-29) | 5 years | 
| Impact of MS on daily life | Multiple Sclerosis Impact Scale (MSIS-29) | Any relapse (maximum 5 years) | 
| Fatigue | Modified Fatigue Impact Scale | Inclusion | 
| Fatigue | Modified Fatigue Impact Scale | 6 Months | 
| Fatigue | Modified Fatigue Impact Scale | 1 Year | 
| Fatigue | Modified Fatigue Impact Scale | 2 years | 
| Fatigue | Modified Fatigue Impact Scale | 3 years | 
| Fatigue | Modified Fatigue Impact Scale | 4 years | 
| Fatigue | Modified Fatigue Impact Scale | 5 years | 
| Fatigue | Modified Fatigue Impact Scale | Any relapse (maximum 5 years) | 
| Visual acuity | 0= low, 10= good | Inclusion | 
| Visual acuity | 0= low, 10= good | 6 Months | 
| Visual acuity | 0= low, 10= good | 1 Year | 
| Visual acuity | 0= low, 10= good | 2 years | 
| Visual acuity | 0= low, 10= good | 3 years | 
| Visual acuity | 0= low, 10= good | 4 years | 
| Visual acuity | 0= low, 10= good | 5 years | 
| Visual acuity | 0= low, 10 good | Any relapse (maximum 5 years) | 
| Low contrast visual acuity | 0= low, 10 good | Inclusion | 
| Low contrast visual acuity | 0= low, 10 good | 6 Months | 
| Low contrast visual acuity | 0= low, 10 good | 1 Year | 
| Low contrast visual acuity | 0= low, 10 good | 2 years | 
| Low contrast visual acuity | 0= low, 10 good | 3 years, | 
| Low contrast visual acuity | 0= low, 10 good | 4 years | 
| Low contrast visual acuity | 0= low, 10 good | 5 years | 
| Low contrast visual acuity | 0= low, 10 good | Any relapse (maximum 5 years) | 
| Relapse description | monofocal, plurifocal | At relapse (maximum 5 years) | 
| Number of new lesions | Measured by MRI | At relapse (maximum 5 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GFAP, NfL