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

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by Assistance Publique - Hôpitaux de Paris
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01651520
First received: July 25, 2012
Last updated: June 13, 2014
Last verified: November 2013
  Purpose

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.


Condition Intervention
Multiple Sclerosis
Drug: PET with 11C-Flumazenil

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Prognosis Value of the Neuronal Damage Detected by Positrons Emission Tomography (PET) With 11C-Flumazenil in Early Multiple Sclerosis.

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • neuronal imaging [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Prognosis value of the neuronal imaging on 2 years evolution (atrophy and EDSS)


Estimated Enrollment: 80
Study Start Date: March 2013
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Relapsing patients < 5 years
Relapsing patients < 5 years
Drug: PET with 11C-Flumazenil
PET with 11C-Flumazenil.
Experimental: relapsing patients < 10 years
relapsing patients < 10 years
Drug: PET with 11C-Flumazenil
PET with 11C-Flumazenil.
Experimental: primary progressive patients < 10 years
primary progressive patients < 10 years
Drug: PET with 11C-Flumazenil
PET with 11C-Flumazenil.
healthy volunteers
healthy volunteers
Drug: PET with 11C-Flumazenil
PET with 11C-Flumazenil.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01651520

Contacts
Contact: Bruno Stankoff, MD, PhD 33 156016262 bruno.stankoff@tnn.aphp.fr

Locations
France
Pitié Salpêtrière Hospital Recruiting
Paris, France, 75013
Contact: Bruno Stankoff, MD, PhD       bruno.stankoff@tnn.aphp.fr   
Principal Investigator: Bruno Stankoff, MD, PhD         
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Bruno Stankoff, MD, PhD APHP
  More Information

No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01651520     History of Changes
Other Study ID Numbers: IDRCB 2011-A00836-35, P100126
Study First Received: July 25, 2012
Last Updated: June 13, 2014
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Neurodegeneration
Disability
Cognition
Prognosis

Additional relevant MeSH terms:
Multiple Sclerosis
Sclerosis
Autoimmune Diseases
Autoimmune Diseases of the Nervous System
Demyelinating Autoimmune Diseases, CNS
Demyelinating Diseases
Immune System Diseases
Nervous System Diseases
Pathologic Processes
Flumazenil
Antidotes
GABA Agents
GABA Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents

ClinicalTrials.gov processed this record on November 20, 2014