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

• ClinicalTrials.gov Identifier: NCT01651520
• Recruitment Status: Unknown
• First Posted: July 27, 2012
• Last Update Posted: August 16, 2017
• Sponsor: Assistance Publique - Hôpitaux de Paris
• Information provided by (Responsible Party): Assistance Publique - Hôpitaux de Paris

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Multiple Sclerosis	Drug: PET with 11C-Flumazenil	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (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.
• Actual Study Start Date: June 2013
• Estimated Primary Completion Date: June 2019
• Estimated Study Completion Date: June 2019

Arms and Interventions

Arm	Intervention/treatment
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.

Outcome Measures

Primary Outcome Measures :

1. neuronal imaging [ Time Frame: 2 years ]
   Prognosis value of the neuronal imaging on 2 years evolution (atrophy and EDSS)

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• 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

Locations

France

Pitié Salpêtrière Hospital

Paris, France, 75013

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

Investigators

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

More Information

• Responsible Party: Assistance Publique - Hôpitaux de Paris
• ClinicalTrials.gov Identifier: NCT01651520
• Other Study ID Numbers: IDRCB 2011-A00836-35; P100126 ( Other Identifier: APHP )
• First Posted: July 27, 2012
• Last Update Posted: August 16, 2017
• Last Verified: August 2017

Keywords provided by Assistance Publique - Hôpitaux de Paris:

Neurodegeneration; Disability; Cognition; Prognosis

Additional relevant MeSH terms:

Multiple Sclerosis; Sclerosis; Pathologic Processes; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Flumazenil; Antidotes; Protective Agents; Physiological Effects of Drugs; GABA Modulators; GABA Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action