Prognosis Value of the Neuronal Damage in Early Multiple Sclerosis

Not Applicable

• Conditions: Multiple Sclerosis
• Interventions: Drug: PET with 11C-Flumazenil

• Registration Number: NCT01651520
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

In this study the investigators will use PET and 11C-Flumazenil to visualize and quantify neuronal injury in the cortex and the deep gray matter of Multiple Sclerosis patients at an early stage. The investigators will follow up patients to determine the prognostic value of this neuronal injury.

Detailed Description

It is now well admitted that multiple sclerosis (MS), which is an inflammatory demyelinating disease of the central nervous system (CNS) is not restricted to white matter, but also involves grey matter, either the cortex or the deep grey matter. The progression of grey matter atrophy measured by MRI during disease course represents an interesting prognosis marker for long term progression, but this marker lack sensitivity and is hard to interpret at the individual level.

In the EAE animal models, an early neuronal damage has been described, characterized both by a synaptic and dendritic loss and by a neuronal apoptosis.

These data strongly suggest that the occurrence of an early neuronal damage during MS course could represent a major prognosis marker. Therefore there is a crucial need for the development of imaging techniques, aimed at visualizing and quantifying neuronal damage in early MS. To date MRI techniques are not able to specifically assess neuronal pathology in vivo.

In this prospective project we will determine the chronology of appearance and the prognosis value of the neuronal damage measured by PET with 11C-Flumazenil, concerning further grey matter atrophy progression and disability progression among a cohort of MS patients with recent onset.

Four groups of subjects will be included: i) patients with a RRMS evolving since less than 5 years (revised Mc Donald criteria, n=20); ii) patients with a RRMS evolving since more than 5 years and less than 10 years (n=20); iii) patients with a primary progressive MS (PPMS) evolving since less than 10 years (n=20); iv) Healthy volunteers matched for age and sex (2/3 matched with RRMS patients; 1/3 matched with PPMS patients).

Each subject will pass a neurologic examination, a neuropsychological testing, a first PET examination with 11C-Flumazenil, a multimodal MRI, with conventional sequences (3DT1, 3D T2 and FLAIR, pre and post contrast T1) and non conventional sequences (MTR, DTI, protonic spectroscopy).

All patients will be followed prospectively with one visit/year consisting in clinical neurological, and neuropsychological evaluations as well as multimodal MRI.

For healthy volunteers a second PET 11C-Flumazenil will also be performed to assess reproducibility and evolution (50% after 1 month, 50% after 1 year).

This study will allow to assess on a larger sample followed prospectively (5 years) the prognosis value of abnormalities detected and quantified by PET with 11C-Flumazenil on further grey matter atrophy progression on MRI and disability progression (EDSS, MSFC, cognitive status). It will also precise the chronology of appearance and the evolution of neuronal damage in MS, and determine the reproducibility of this technique. Results should provide a new and more efficient prognosis marker for early MS.

Study Timeline

• Study First Submitted: 2012-07-25
• Study First Submitted QC: 2012-07-26
• Study First Posted: 2012-07-27
• Study Start: 2013-06
• Status Verified: 2017-08
• Last Update Submitted: 2017-08-14
• Last Update Posted: 2017-08-16
• Primary Completion: 2019-06
• Study Completion: 2019-06

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

Four groups of subjects will be included:

• patients with a RRMS evolving since less than 5 years (revised Mc Donald criteria, n=20);
• patients with a RRMS evolving since more than 5 years and less than 10 years (n=20);
• patients with a primary progressive MS (PPMS) evolving since less than 10 years (n=20);
• Healthy volunteers matched for age and sex (2/3 matched with RRMS patients; 1/3 matched with PPMS patients).

Exclusion Criteria

• Lack of social insurance
• Pregnancy
• Age > 55
• Therapy with benzodiazepine

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
primary progressive patients < 10 years	PET with 11C-Flumazenil	primary progressive patients \< 10 years
healthy volunteers	PET with 11C-Flumazenil	healthy volunteers
Relapsing patients < 5 years	PET with 11C-Flumazenil	Relapsing patients \< 5 years
relapsing patients < 10 years	PET with 11C-Flumazenil	relapsing patients \< 10 years

Primary Outcome Measures

Name	Time	Method
neuronal imaging	2 years	Prognosis value of the neuronal imaging on 2 years evolution (atrophy and EDSS)

Trial Locations

Locations (1)

Pitié Salpêtrière Hospital; 🇫🇷 Paris, France