Imaging of Intracerebral Inflammation in MS

Not Applicable

Completed

• Conditions: Multiple Sclerosis, Secondary Progressive; Multiple Sclerosis, Primary Progressive; Multiple Sclerosis, Relapsing-Remitting
• Interventions: Drug: 18F-DPA-714 and 18F-FDG

• Registration Number: NCT02305264
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief 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

Study Timeline

• Study Start: 2012-03-19
• Study First Submitted: 2013-01-25
• Study First Submitted QC: 2014-11-27
• Study First Posted: 2014-12-02
• Primary Completion: 2018-09-10
• Study Completion: 2018-09-10
• Status Verified: 2022-09
• Last Update Submitted: 2022-09-14
• Last Update Posted: 2022-09-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 61

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
PET -18F-DPA-714 and 18F-FDG	18F-DPA-714 and 18F-FDG	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.

Primary Outcome Measures

Name	Time	Method
Whole brain Binding Potential (BP) of 18F-DPA-714	D0	Quantification of microglial compartmentalized inflammation within the brain by PET with 18F-DPA-714 in MS patients and healthy controls

Secondary Outcome Measures

Name	Time	Method
Binding potential of 18F-DPA-714 in subgroups of MS patients	D0	To compare binding potential of 18F-DPA-714 in subgroups of MS patients (secondary progressive, primary progressive, relapsing remitting)
Predictive value of PET 18F-DPA-714 BP on MRI metrics	2 years	To determine the predictive value of brain microglial inflammation on subsequent brain atrophy progression after a follow up period of two years.
Binding potential of 18F-DPA-714 in segmented brain regions	D0	To compare binding potential of 18F-DPA-714 in segmented brain regions: white matter, gray matter, white matter lesions
Predictive value of PET 18F-DPA-714 BP on neurological clinical metrics	2 years	To determine the predictive value of brain microglial inflammation on subsequent neurological impairment progression after a follow up period of two years.

Trial Locations

Locations (2)

Pitie Salpetriere Hospital; 🇫🇷 Paris, France

Saint Antoine Hospital; 🇫🇷 Paris, France