Prognosis Value of the Neuronal Damage in Early Multiple Sclerosis (Flumatep_2)

August 14, 2017 updated by: Assistance Publique - Hôpitaux de Paris

Prognosis Value of the Neuronal Damage Detected by Positrons Emission Tomography (PET) With 11C-Flumazenil in Early Multiple Sclerosis.

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

60

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Paris, France, 75013
        • Pitié Salpétrière Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: healthy volunteers
Drug: PET with 11C-Flumazenil
PET with 11C-Flumazenil.
Experimental: Relapsing patients < 5 years
Drug: PET with 11C-Flumazenil
PET with 11C-Flumazenil.
Experimental: relapsing patients < 10 years
Drug: PET with 11C-Flumazenil
PET with 11C-Flumazenil.
Experimental: primary progressive patients < 10 years
Drug: PET with 11C-Flumazenil
PET with 11C-Flumazenil.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
neuronal imaging
Time Frame: 2 years
Prognosis value of the neuronal imaging on 2 years evolution (atrophy and EDSS)
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique - Hôpitaux de Paris

Investigators

  • Principal Investigator: Bruno Stankoff, MD, PhD, APHP

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2013

Primary Completion (Anticipated)

June 1, 2019

Study Completion (Anticipated)

June 1, 2019

Study Registration Dates

First Submitted

July 25, 2012

First Submitted That Met QC Criteria

July 26, 2012

First Posted (Estimate)

July 27, 2012

Study Record Updates

Last Update Posted (Actual)

August 16, 2017

Last Update Submitted That Met QC Criteria

August 14, 2017

Last Verified

August 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IDRCB 2011-A00836-35
  • P100126 (Other Identifier: APHP)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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