Imaging of Intracerebral Inflammation in MS
Condition: Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis, Secondary Progressive; Multiple Sclerosis, Primary Progressive
MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis, Chronic Progressive; Sclerosis; Inflammation
Study type: Interventional

Summary: 
      In this study we plan to image the compartmentalized inflammation in MS using molecular
      imaging by positron emission tomography (PET) with a very highly resolutive camera. Two
      tracers will be studied and compared: i) [18F]DPA-714, which bind to the peripheral
      benzodiazepine receptor (PBR), a target mainly expressed by activated microglial cells. This
      new ligand for PBR displays several advantages compared to the existing reference compound
      PK11195 in term of brain entrance, signal to noise ratio, and radiolabelling possibility with
      [18F] ii) [18F]-fluoro-desoxy-glucose ([18F]FDG), which should reflect glucose metabolism in
      activated immune cells in the white matter. Progressive MS patients (secondary progressive
      and primary progressive) will be compared to relapsing-remitting patients and to healthy
      volunteers. All subjects will pass a complete neurological evaluation and a multimodal MRI to
      document clinical disability and tissue injury. A clinical and radiological follow up will
      then be performed for a 2-year period. This study should help to understand the contribution
      of the intracerebral inflammation on the progression of disability and could provide a
      surrogate marker for further therapeutic trials in chronic progressive MS.
    

Detailed description: 
      Study design This study is a prospective cross-sectional controlled multicentric clinical
      study in 45 MS patients and 20 controls.

      Four groups of person will be included and compared:

        -  Group I: 20 healthy volunteers aging from 18 to 65 years. These healthy volunteers will
           be matched for age and sex with patients (1/2).

        -  Group II: 15 patients aging from 18 to 65 years with relapsing-remitting (RRMS), with
           less than 10 years of evolution since the first manifestation and no recent relapse.

        -  Group III: 15 patients aging from 18 to 65 years with secondary progressive MS (SPMS),
           with less than 10 years of evolution since the occurrence of the secondary progressive
           phase.

        -  Group III: 15 patients aging from 18 to 65 years with primary progressive MS (PPMS)
           diagnosed since less than 10 years.

      Study centres MS patients and the 20 healthy volunteers will be recruited in the Hospital
      Pitie-Salpetriere

      MS patients will be recruited in the Hospital Tenon

      This study will be performed by complementary teams already collaborating on molecular
      imaging trials in MS (which assess neuronal loss or demyelination/remyelination): i) the
      "Centre d'Investigation Clinique" (Salpetriere hospital, Paris), which is strongly
      experienced in the coordination of clinical and translational research on MS; ii) the CENIR
      (centre for neuroimaging research, Salpetriere hospital, Paris) a specialized MRI centre for
      research on neurological diseases; iii) the SHFJ (DSV, CEA, ORSAY) which is a world class
      molecular imaging centre;

      Study duration Per patient the study will last two years Per control the study will last up
      to 8 weeks
    

Intervention name(s): 18F-DPA-714 and 18F-FDG
Intervention type(s): Drug
Intervention description(s): Positron emission tomography (PET) imaging following the injection of 2 radiotracers (here considered as the drugs): 1) 18F-DPA-714 ii) 18F-FDG. PET -18F-DPA-714, dose 5mCi (185MBq), will be injected via an arm intravenous catheter.
18F-FDG , dose 5mci(185MBq), will be injected via an arm intravenous catheter.
Intervention MeSH terms: Fluorodeoxyglucose F18
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic