Identification of Retinal Perivascular Inflammation in Patients With Multiple Sclerosis Using Adaptive Optics (RETIMUS)

Multiple Sclerosis Clinical Trial

— RETIMUS  

Official title:

Identification of Retinal Perivascular Inflammation in Patients With Multiple Sclerosis Using Adaptive Optics

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04289909
• Other study ID #: 19-25
• Status: Not yet recruiting
• Phase: N/A
• Start date: March 2020
• Est. completion date: October 2022

Study information

• Verified date: February 2020
• Source: Institut National de la Santé Et de la Recherche Médicale, France
• Contact: Céline Louapre
• Phone: + 33 1 42 16 57 66
• Email: celine.louapre[@]aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: October 2022
• Est. primary completion date: October 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Eye Diseases
• Inflammation
• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting
• Nervous System Diseases
• Neuritis
• Optic Nerve Diseases
• Optic Neuritis
• Progressive Multiple Sclerosis
• Relapsing Remitting Multiple Sclerosis
• Sclerosis

Intervention

Other:
• Adaptive Optics Ophthalmoscopy (AOO)
AOO will permit to detect and quantify retinal perivascular inflammation in patients with MS in comparison to Healthy volunteers (control group)

Locations

Country	Name	City	State
France	Institut du Cerveau et de la Moelle epiniere - Hopital Pitie Salpetriere	Paris

Sponsors (2)

Lead Sponsor	Collaborator
Institut National de la Santé Et de la Recherche Médicale, France	Biogen

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Quantification of retinal perivascular cuff width across MS phenotypes	The primary endpoint is to quantify retinal perivascular cuff width across MS phenotypes, compared among a group of control at baseline.	Baseline
Secondary	Variation of size of perivascular sheathing	Variation of size of perivascular sheathing along retinal vessels in the posterior pole during follow up (at month 3 and month 6) in patients with MS and a group of control	month 3 and month 6
Secondary	Clinical disability measure with EDSS	Evolution of Clinical disability: Expanded Disability Status Scale (EDSS: 0: normal neurological exam; 10 : death of the patient) at month 3 for MS patients with optic neuritis and at month 6 for all MS patients	month 3 and month 6
Secondary	Clinical disability measured with MSFC	Evolution of Clinical disability: Multiple Sclerosis Functional Composite (MSFC) at month 3 for MS patients with optic neuritis and at month 6 for all MS patients	month 3 and month 6
Secondary	Number of relapses	Evolution of Clinical disability: number of relapses at month 3 for MS patients with optic neuritis and at month 6 for all MS patients	month 3 and month 6
Secondary	Presence of disc oedema measured at Optical Coherence Tomography (OCT) measurements	Evolution of OCT measurements (presence of disc oedema) at month 3 for MS patients with optic neuritis and at month 6 for all MS patients	month 3 and month 6
Secondary	RNLF thickness measured at Optical Coherence Tomography (OCT) measurements	Evolution of OCT measurements : retinal nerve fiber layer thickness (RNFL, µm) at month 3 for MS patients with optic neuritis and at month 6 for all MS patients	month 3 and month 6
Secondary	parenchymal T2 lesion volume at MRI	Evolution of MRI metrics: parenchymal T2 lesion volume	Baseline
Secondary	gadolinium enhanced T1 lesion at MRI	Evolution of MRI metrics: gadolinium enhanced T1 lesion	Baseline
Secondary	optic nerve cross-sectional area at MRI	Evolution of MRI metrics: optic nerve cross-sectional area	Baseline
Secondary	Hyperintensity on the optic nerve at MRI	Evolution of MRI metrics: Hyperintensity on the optic nerve	Baseline