Clinical trial NCT04289909: Identification of Retinal Perivascular Inflammation in Patients With Multiple Sclerosis Using Adaptive Optics (RETIMUS)
Official title: Identification of Retinal Perivascular Inflammation in Patients With Multiple Sclerosis Using Adaptive Optics
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Relapsing Remitting Multiple Sclerosis
Progressive Multiple Sclerosis
Optic Neuritis
Eye Diseases
Optic Nerve Diseases
Nervous System Diseases
Multiple Sclerosis
Keywords: relapsing remitting Multiple sclerosis
Progressive Multiple Sclerosis
Optic neuritis
multiple sclerosis
adaptive optics
eye disease
peripheral nervous system disease
Lead sponsor: Institut National de la Santé Et de la Recherche Médicale, France
Sponsor class: OTHER_GOV
Collaborators: name: Biogen
First posted: 2020-02-28
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: Using a technique called adaptive optics imaging applied on retina, investigators aim to gain access to vascular changes that could occur early in the course of Multiple Sclerosis (MS) and which could reflect vascular changes occurring along the optic nerve of the brain parenchyma. Indeed, our team has been able to develop a quantitative method to measure the perivascular infiltrate in the retina of patients with various inflammatory retinal disease. It has been observed in MS patients that this perivascular infiltrate can also be detected in the retina. However, its distribution across MS phenotypes (relapsing or progressive MS, with and without optic neuritis) is still unknown.

Detailed description: This is a monocentric pathophysiological, interventional, prospective, open label, non-randomized pilot study which aims to identify in patients with MS at different stages if the presence of retinal perivascular inflammation can be detected and quantified using adaptive optics, which is a non-invasive examination.

Investigators will recruit MS patients in 3 subgroups, depending on their phenotype (Relapsing Remitting Multiple Sclerosis (RRMS) without optic neuritis, RRMS with optic neuritis, progressive MS), with 15 patients in each group.

15 healthy volunteers (HV) will also be enrolled.

The comparison of these groups is necessary to determine if there are significant differences, allowing us to highlight biomarkers in MS patients in order to enable highly efficient and robust trials designs in the future.

To test the hypothesis, the study has 3 visits over 6 months (M0, M3 and M6). Neurological evaluation, blood sample, imaging, ophthalmologic evaluation and Adaptive optics ophthalmoscopy assessments will be performed.

Eligibility criteria: Inclusion Criteria:

Group 1:

* Age between 18 and 60 years old.
* Relapsing remitting MS (criteria of McDonald 2017)
* Less than 10 years of disease duration
* Subject who has never presented a clinical episode of optic neuritis
* Affiliation to a social security scheme or beneficiary of such a scheme

Group 2:

* Age between 18 and 60 years old
* Relapsing remitting MS (criteria of McDonald 2017)
* Less than 10 years of disease duration
* Subject presenting an acute episode of retrobulbar optic neuritis within 3 months from onset
* After optimal treatment for the retrobulbar optic neuritis
* Affiliation to a social security scheme or beneficiary of such a scheme

Group 3:

* Age between 18 and 60 years old
* Primary or Secondary progressive multiple sclerosis within 10 years of progressive phase;
* Affiliation to a social security scheme or beneficiary of such a scheme

Group 4 (Healthy Subjects):

* Age between 18 and 60 years old
* Affiliation to a social security scheme or beneficiary of such a scheme

Exclusion Criteria:

For all patients (Group 1; 2; 3):

* Corticosteroid treatment within one month from inclusion
* Other neurological, ophthalmologic or systemic disease;
* Severe symptoms of uncontrolled chronic disease (renal, hepatic, hematologic, gastro-intestinal, pulmonary or cardiac or any intercurrent uncontrolled disease at inclusion)
* Severe renal dysfunction (glomerular filtration rate \< 30mL/min). This non-inclusion criteria will be verified by serum creatinine test within six months from inclusion;
* Contraindication for MRI;
* Pregnancy or breast-feeding;
* Unwillingness to be informed in case of abnormal MRI (with a significant medical anomaly)
* Incapacity to understand or sign the consent form;
* Adults legally protected (under judicial protection, guardianship, or supervision), persons deprived of their liberty.

For healthy subjects (Group 4):

* Neurological, ophthalmologic or systemic disease;
* Severe symptoms of uncontrolled chronic disease (renal, hepatic, hematologic, gastro-intestinal, pulmonary or cardiac or any intercurrent uncontrolled disease at inclusion);
* Contraindication for MRI;
* Pregnancy or breast-feeding;
* Unwillingness to be informed in case of abnormal MRI (with a significant medical anomaly)
* Incapacity to understand or sign the consent form;
* Adults legally protected (under judicial protection, guardianship, or supervision), persons deprived of their liberty.

Primary outcomes:
measure: Quantification of retinal perivascular cuff width across MS phenotypes
timeFrame: Baseline
Secondary outcomes:
measure: Variation of size of perivascular sheathing
timeFrame: month 3 and month 6
measure: Clinical disability measure with EDSS
timeFrame: month 3 and month 6
measure: Clinical disability measured with MSFC
timeFrame: month 3 and month 6
measure: Number of relapses
timeFrame: month 3 and month 6
measure: Presence of disc oedema measured at Optical Coherence Tomography (OCT) measurements
timeFrame: month 3 and month 6
measure: RNLF thickness measured at Optical Coherence Tomography (OCT) measurements
timeFrame: month 3 and month 6
measure: parenchymal T2 lesion volume at MRI
timeFrame: Baseline
measure: gadolinium enhanced T1 lesion at MRI
timeFrame: Baseline
measure: optic nerve cross-sectional area at MRI
timeFrame: Baseline
measure: Hyperintensity on the optic nerve at MRI
timeFrame: Baseline
Other outcomes:
Locations:
city: Paris
country: France
facility: Institut du Cerveau et de la Moelle epiniere - Hopital Pitie Salpetriere
Study officials:
affiliation: Institut du Cerveau et de la Moelle Epinière
name: Celine Louapre, MD, PHD
role: PRINCIPAL_INVESTIGATOR
References: