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

Primary Purpose

Relapsing Remitting Multiple Sclerosis, Progressive Multiple Sclerosis, Optic Neuritis

Status
Unknown status
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Adaptive Optics Ophthalmoscopy (AOO)
Sponsored by
Institut National de la Santé Et de la Recherche Médicale, France
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Relapsing Remitting Multiple Sclerosis focused on measuring relapsing remitting Multiple sclerosis, Progressive Multiple Sclerosis, Optic neuritis, multiple sclerosis, adaptive optics, eye disease, peripheral nervous system disease

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • Institut du Cerveau et de la Moelle epiniere - Hopital Pitie Salpetriere

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Other

Arm Label

MS patients

Control group

Arm Description

RRMS Patients with optic neuritis, RRMS patients without optic neuritis or Progressive MS patients

Healthy volunteers

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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
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
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
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
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
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
parenchymal T2 lesion volume at MRI
Evolution of MRI metrics: parenchymal T2 lesion volume
gadolinium enhanced T1 lesion at MRI
Evolution of MRI metrics: gadolinium enhanced T1 lesion
optic nerve cross-sectional area at MRI
Evolution of MRI metrics: optic nerve cross-sectional area
Hyperintensity on the optic nerve at MRI
Evolution of MRI metrics: Hyperintensity on the optic nerve

Full Information

First Posted
February 25, 2020
Last Updated
February 26, 2020
Sponsor
Institut National de la Santé Et de la Recherche Médicale, France
Collaborators
Biogen
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1. Study Identification

Unique Protocol Identification Number
NCT04289909
Brief Title
Identification of Retinal Perivascular Inflammation in Patients With Multiple Sclerosis Using Adaptive Optics (RETIMUS)
Acronym
RETIMUS
Official Title
Identification of Retinal Perivascular Inflammation in Patients With Multiple Sclerosis Using Adaptive Optics
Study Type
Interventional

2. Study Status

Record Verification Date
February 2020
Overall Recruitment Status
Unknown status
Study Start Date
March 2020 (Anticipated)
Primary Completion Date
October 2022 (Anticipated)
Study Completion Date
October 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institut National de la Santé Et de la Recherche Médicale, France
Collaborators
Biogen

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
MS patients
Arm Type
Other
Arm Description
RRMS Patients with optic neuritis, RRMS patients without optic neuritis or Progressive MS patients
Arm Title
Control group
Arm Type
Other
Arm Description
Healthy volunteers
Intervention Type
Other
Intervention Name(s)
Adaptive Optics Ophthalmoscopy (AOO)
Intervention Description
AOO will permit to detect and quantify retinal perivascular inflammation in patients with MS in comparison to Healthy volunteers (control group)
Primary Outcome Measure Information:
Title
Quantification of retinal perivascular cuff width across MS phenotypes
Description
The primary endpoint is to quantify retinal perivascular cuff width across MS phenotypes, compared among a group of control at baseline.
Time Frame
Baseline
Secondary Outcome Measure Information:
Title
Variation of size of perivascular sheathing
Description
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
Time Frame
month 3 and month 6
Title
Clinical disability measure with EDSS
Description
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
Time Frame
month 3 and month 6
Title
Clinical disability measured with MSFC
Description
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
Time Frame
month 3 and month 6
Title
Number of relapses
Description
Evolution of Clinical disability: number of relapses at month 3 for MS patients with optic neuritis and at month 6 for all MS patients
Time Frame
month 3 and month 6
Title
Presence of disc oedema measured at Optical Coherence Tomography (OCT) measurements
Description
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
Time Frame
month 3 and month 6
Title
RNLF thickness measured at Optical Coherence Tomography (OCT) measurements
Description
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
Time Frame
month 3 and month 6
Title
parenchymal T2 lesion volume at MRI
Description
Evolution of MRI metrics: parenchymal T2 lesion volume
Time Frame
Baseline
Title
gadolinium enhanced T1 lesion at MRI
Description
Evolution of MRI metrics: gadolinium enhanced T1 lesion
Time Frame
Baseline
Title
optic nerve cross-sectional area at MRI
Description
Evolution of MRI metrics: optic nerve cross-sectional area
Time Frame
Baseline
Title
Hyperintensity on the optic nerve at MRI
Description
Evolution of MRI metrics: Hyperintensity on the optic nerve
Time Frame
Baseline

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Céline Louapre
Phone
+ 33 1 42 16 57 66
Email
celine.louapre@aphp.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Celine Louapre, MD, PHD
Organizational Affiliation
Institut du Cerveau et de la Moelle Epinière
Official's Role
Principal Investigator
Facility Information:
Facility Name
Institut du Cerveau et de la Moelle epiniere - Hopital Pitie Salpetriere
City
Paris
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Céline Louapre, MD, PH
First Name & Middle Initial & Last Name & Degree
Michel Paques, PU, PH

12. IPD Sharing Statement

Learn more about this trial

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

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