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 (NFL OCT)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Diagnostic test: Brain MRI; Diagnostic test: Spinal Cord MRI; Diagnostic test: Retinal imaging

• Study Type: Observational
• Enrollment (Actual): 200

Contacts and Locations

Study Locations

• France
  • Nîmes, France, 30029
    • CHU de Nîmes

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population is composed of consecutive adult patients, of both sexes, recruited during consultations for a CIS, RRMS or progressive MS at the Neurology department of Nîmes University Hospital (CHU). The patients recruited will have an EDSS score comprised between 0 - 7.0.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
MS patients	Diagnostic test: Brain MRI; 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.; Diagnostic test: Spinal Cord MRI; Sagittal T2 Sagittal T1 with Gadolinium injection; Diagnostic test: Retinal imaging; spectral-domain high definition optical coherence tomography

What is the study measuring?

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
Expanded Disability Status Scale	Eight functional systems scored on a scale of 0 (no disability) to 5 or 6 (more severe disability)	3 years
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)	3.5 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)

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nīmes
• Collaborators: Institut de Recherches en Biothérapie
• Investigators: Principal Investigator: Eric Thouvenot, CHU Nîmes

Study record dates

Study Major Dates

• Study Start (Actual): June 25, 2019
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: April 16, 2021
• First Submitted That Met QC Criteria: April 22, 2021
• First Posted (Actual): April 27, 2021

Study Record Updates

• Last Update Posted (Actual): February 26, 2024
• Last Update Submitted That Met QC Criteria: February 23, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: GFAP; NfL
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Pathological Conditions, Anatomical; Multiple Sclerosis; Sclerosis; Atrophy
• Other Study ID Numbers: CIVI/2018/ET-01; 2018-A03152-53 (Other Identifier: ANSM)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No