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

• ClinicalTrials.gov Identifier: NCT04289909
• Recruitment Status: Not yet recruiting
• First Posted: February 28, 2020
• Last Update Posted: February 28, 2020
• Sponsor: Institut National de la Santé Et de la Recherche Médicale, France
• Collaborator: Biogen
• Information provided by (Responsible Party): Institut National de la Santé Et de la Recherche Médicale, France

Tracking Information

• First Submitted Date: February 25, 2020
• First Posted Date: February 28, 2020
• Last Update Posted Date: February 28, 2020
• Estimated Study Start Date: March 2020
• Estimated Primary Completion Date: October 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 26, 2020)

Quantification of retinal perivascular cuff width across MS phenotypes [ Time Frame: Baseline ]

The primary endpoint is to quantify retinal perivascular cuff width across MS phenotypes, compared among a group of control at baseline.

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: February 26, 2020)

• Variation of size of perivascular sheathing [ Time Frame: month 3 and month 6 ]
  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 [ Time Frame: month 3 and month 6 ]
  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 [ Time Frame: month 3 and month 6 ]
  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 [ Time Frame: month 3 and month 6 ]
  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 [ Time Frame: month 3 and month 6 ]
  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 [ Time Frame: month 3 and month 6 ]
  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 [ Time Frame: Baseline ]
  Evolution of MRI metrics: parenchymal T2 lesion volume
• gadolinium enhanced T1 lesion at MRI [ Time Frame: Baseline ]
  Evolution of MRI metrics: gadolinium enhanced T1 lesion
• optic nerve cross-sectional area at MRI [ Time Frame: Baseline ]
  Evolution of MRI metrics: optic nerve cross-sectional area
• Hyperintensity on the optic nerve at MRI [ Time Frame: Baseline ]
  Evolution of MRI metrics: Hyperintensity on the optic nerve

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Other

Condition

• Relapsing Remitting Multiple Sclerosis
• Progressive Multiple Sclerosis
• Optic Neuritis
• Eye Diseases
• Optic Nerve Diseases
• Nervous System Diseases
• Multiple 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)

Study Arms

• MS patients
  RRMS Patients with optic neuritis, RRMS patients without optic neuritis or Progressive MS patients
  Intervention: Other: Adaptive Optics Ophthalmoscopy (AOO)
• Control group
  Healthy volunteers
  Intervention: Other: Adaptive Optics Ophthalmoscopy (AOO)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: February 26, 2020): 60
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: October 2022
• Estimated Primary Completion Date: October 2022 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 60 Years (Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Céline Louapre; + 33 1 42 16 57 66; celine.louapre@aphp.fr

• Listed Location Countries: France

Administrative Information

• NCT Number: NCT04289909
• Other Study ID Numbers: 19-25
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Institut National de la Santé Et de la Recherche Médicale, France
• Original Responsible Party: Same as current
• Current Study Sponsor: Institut National de la Santé Et de la Recherche Médicale, France
• Original Study Sponsor: Same as current
• Collaborators: Biogen

Investigators

• Principal Investigator: Celine Louapre, MD, PHD; Institut du Cerveau et de la Moelle Epinière

• PRS Account: Institut National de la Santé Et de la Recherche Médicale, France
• Verification Date: February 2020