Clinical trial NCT03656055: Analysis of Neurodegenerative Process Within Visual Ways In Multiple Sclerosis
Official title: Study of the Link Between Retinal Atrophy and Demyelinating Inflammatory Processes on Visual Pathways in Relapsing Multiple Sclerosis in Magnetic Resonance Imaging and Optical Coherence Tomography
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Multiple Sclerosis
Keywords: MRI
axonal loss
MS
OCT
Lead sponsor: University Hospital, Lille
Sponsor class: OTHER
First posted: 2018-09-04
Enrollment: 108
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: RRMS treated by natalizumab for more than 6 months in order to measure patients with a lower risk of relapse

Brief summary: This study will interest in the pathophysiology of silent retinal axonal loss in multiple sclerosis. Recent studies have suggested that silent retinal axonal loss (no past history of optic neuritis \[ON\]) may be due to inflammatory lesions within the optic radiations and a transsynaptic degenerative process. The objective is to measure the exact role of silent optic nerve lesion in the occurrence of silent retinal axonal loss by performing OCT, brain and optic nerve MRI in a cohort of patients without recent disease activity.

Detailed description: This study will interest in the neurodegenerative process reported in multiple sclerosis within the visual ways.

Symptomatic and asymptomatic retinal axonal loss in multiple sclerosis (MS) have largely been described. Many recent optical coherence tomography (OCT) studies have suggested that subclinical retinal axonal loss (no past history of optic neuritis \[ON\]) observed in MS mainly due to inflammatory and demyelinating lesions within the optic radiations and a retrograde transsynaptic degenerative process. None of these studies clearly tried to investigate the role of asymptomatic optic nerve lesion(s) in subclinical retinal axonal loss occurence.

The main objective of the study is to measure the exact role of silent optic nerve lesion in the occurrence of silent retinal axonal loss by performing OCT, brain and optic nerve MRI. The study will focus on a cohort of patients without recent disease activity in order to exclude or minimize the risk of recent and old lesion occurence on the visual ways, which could be a bias in our analysis.

Eligibility criteria: Inclusion Criteria:

* Relapsing Remitting Multiple Sclerosis (RRMS) patients treated by natalizumab for more than 6 months
* JohnCunninghamVirus (JCV) index \< 0.9
* patients followed in our MS center from the beginning of the disease

Exclusion Criteria:

* ophthalmologic diseases
* diabetes mellitus
* contra-indication to MRI

Primary outcomes:
measure: Study of asymptomatic retinal atrophy in multiple sclerosis and asymptomatic optic nerve demyelinating lesion
timeFrame: Day 1 (cross-sectional study)
Secondary outcomes:
measure: Evaluation of the link between asymptomatic retinal atrophy in multiple sclerosis and intensity of demyelinating process all along the optic ways (from the retina to the visual cortex)
timeFrame: Day 1 (cross-sectional study)
measure: Evaluation of the link between symptomatic retinal atrophy in multiple sclerosis and intensity of demyelinating process all along the optic ways (from the retina to the visual cortex)
timeFrame: Day 1 (cross-sectional study)
measure: Evaluation of the link between retinal atrophy and visual connectivity
timeFrame: Day 1 (cross-sectional study)
measure: Evaluation of the link between visual disability and MRI parameters measuring intensity of demyelinating process all along the optic ways (from the retina to the visual cortex)
timeFrame: Day 1 (cross-sectional study)
Other outcomes:
Locations:
city: Lille
country: France
facility: Hôpital Roger Salengro, CHRU
Study officials:
affiliation: University Hospital, Lille
name: Olivier Outteryck, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hodel J, Outteryck O, Bocher AL, Zephir H, Lambert O, Benadjaoud MA, Chechin D, Pruvo JP, Vermersch P, Leclerc X. Comparison of 3D double inversion recovery and 2D STIR FLAIR MR sequences for the imaging of optic neuritis: pilot study. Eur Radiol. 2014 Dec;24(12):3069-75. doi: 10.1007/s00330-014-3342-3. Epub 2014 Aug 23.
citation: Hadhoum N, Hodel J, Defoort-Dhellemmes S, Duhamel A, Drumez E, Zephir H, Pruvo JP, Leclerc X, Vermersch P, Outteryck O. Length of optic nerve double inversion recovery hypersignal is associated with retinal axonal loss. Mult Scler. 2016 Apr;22(5):649-58. doi: 10.1177/1352458515598021. Epub 2015 Jul 30.
citation: Gabilondo I, Martinez-Lapiscina EH, Martinez-Heras E, Fraga-Pumar E, Llufriu S, Ortiz S, Bullich S, Sepulveda M, Falcon C, Berenguer J, Saiz A, Sanchez-Dalmau B, Villoslada P. Trans-synaptic axonal degeneration in the visual pathway in multiple sclerosis. Ann Neurol. 2014 Jan;75(1):98-107. doi: 10.1002/ana.24030. Epub 2014 Jan 2.
citation: Jindahra P, Petrie A, Plant GT. The time course of retrograde trans-synaptic degeneration following occipital lobe damage in humans. Brain. 2012 Feb;135(Pt 2):534-41. doi: 10.1093/brain/awr324. Epub 2012 Feb 1.
citation: Petzold A, Balcer LJ, Calabresi PA, Costello F, Frohman TC, Frohman EM, Martinez-Lapiscina EH, Green AJ, Kardon R, Outteryck O, Paul F, Schippling S, Vermersch P, Villoslada P, Balk LJ; ERN-EYE IMSVISUAL. Retinal layer segmentation in multiple sclerosis: a systematic review and meta-analysis. Lancet Neurol. 2017 Oct;16(10):797-812. doi: 10.1016/S1474-4422(17)30278-8. Epub 2017 Sep 12.
citation: Martinez-Lapiscina EH, Arnow S, Wilson JA, Saidha S, Preiningerova JL, Oberwahrenbrock T, Brandt AU, Pablo LE, Guerrieri S, Gonzalez I, Outteryck O, Mueller AK, Albrecht P, Chan W, Lukas S, Balk LJ, Fraser C, Frederiksen JL, Resto J, Frohman T, Cordano C, Zubizarreta I, Andorra M, Sanchez-Dalmau B, Saiz A, Bermel R, Klistorner A, Petzold A, Schippling S, Costello F, Aktas O, Vermersch P, Oreja-Guevara C, Comi G, Leocani L, Garcia-Martin E, Paul F, Havrdova E, Frohman E, Balcer LJ, Green AJ, Calabresi PA, Villoslada P; IMSVISUAL consortium. Retinal thickness measured with optical coherence tomography and risk of disability worsening in multiple sclerosis: a cohort study. Lancet Neurol. 2016 May;15(6):574-84. doi: 10.1016/S1474-4422(16)00068-5. Epub 2016 Mar 18.