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Imaging of Intracerebral Inflammation in MS (INFLASEP)

Primary Purpose

Multiple Sclerosis, Relapsing-Remitting, Multiple Sclerosis, Secondary Progressive, Multiple Sclerosis, Primary Progressive

Status
Completed
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
18F-DPA-714 and 18F-FDG
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Multiple Sclerosis, Relapsing-Remitting

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion criteria

Healthy volunteers (group I, n=20)

  • Aged 18-65 years;
  • Able to understand the objectives and procedures of the study, and who give inform consent.

Patients with relapsing-remitting MS (group II, n=15)

  • Aged 18-65 years
  • Clinically definite MS according to McDonald revised criteria
  • Less than 10 year of evolution
  • No clinical relapse during the past 3 months
  • Able to understand the objectives and procedures of the study, and who give inform consent

Patients with progressive MS (group III and IV, n=15 per group)

  • Aged 18-65 years
  • Clinically definite MS according to McDonald revised criteria
  • SPMS evolving since more than 10 years for group III (n = 15).
  • PPMS evolving since less than 10 years for group IV (n=15).
  • Each progressive patient should have experienced a significant progression during the 2 years preceding the inclusion (with an estimated progression of the EDSS score of at least 0.5 point).
  • No clinical relapse during the past 3 months
  • Able to understand the objectives and procedures of the study, and who give inform consent.

Exclusion criteria

  • Any reason, which does not allow performing MRI: claustrophobia, pace-maker or intra-ocular foreign body for example.
  • For women: pregnancy, lactation, lack of efficient contraception. At visit 2, a positive pregnancy test will lead to exclude the patient.
  • Uncontrolled diabetes
  • Current symptoms of severe or uncontrolled renal, hepatic, hematological, gastrointestinal pulmonary or cardiac disease.
  • Positive HIV test
  • Prior participation in other research protocols or clinical care in the last year such that radiation exposure would exceed the annual guidelines.
  • Other chronic neurological disease.

Sites / Locations

  • Saint Antoine Hospital
  • Pitie Salpetriere Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

PET -18F-DPA-714 and 18F-FDG

Arm Description

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Full Information

First Posted
January 25, 2013
Last Updated
September 14, 2022
Sponsor
Assistance Publique - Hôpitaux de Paris
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1. Study Identification

Unique Protocol Identification Number
NCT02305264
Brief Title
Imaging of Intracerebral Inflammation in MS
Acronym
INFLASEP
Official Title
Imaging of Intracerebral Inflammation in the Progressive Phase of Multiple Sclerosis
Study Type
Interventional

2. Study Status

Record Verification Date
September 2022
Overall Recruitment Status
Completed
Study Start Date
March 19, 2012 (Actual)
Primary Completion Date
September 10, 2018 (Actual)
Study Completion Date
September 10, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis, Relapsing-Remitting, Multiple Sclerosis, Secondary Progressive, Multiple Sclerosis, Primary Progressive

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
61 (Actual)

8. Arms, Groups, and Interventions

Arm Title
PET -18F-DPA-714 and 18F-FDG
Arm Type
Experimental
Arm Description
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 Type
Drug
Intervention Name(s)
18F-DPA-714 and 18F-FDG
Intervention Description
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.
Primary Outcome Measure Information:
Title
Whole brain Binding Potential (BP) of 18F-DPA-714
Description
Quantification of microglial compartmentalized inflammation within the brain by PET with 18F-DPA-714 in MS patients and healthy controls
Time Frame
D0
Secondary Outcome Measure Information:
Title
Binding potential of 18F-DPA-714 in segmented brain regions
Description
To compare binding potential of 18F-DPA-714 in segmented brain regions: white matter, gray matter, white matter lesions
Time Frame
D0
Title
Binding potential of 18F-DPA-714 in subgroups of MS patients
Description
To compare binding potential of 18F-DPA-714 in subgroups of MS patients (secondary progressive, primary progressive, relapsing remitting)
Time Frame
D0
Title
Predictive value of PET 18F-DPA-714 BP on neurological clinical metrics
Description
To determine the predictive value of brain microglial inflammation on subsequent neurological impairment progression after a follow up period of two years.
Time Frame
2 years
Title
Predictive value of PET 18F-DPA-714 BP on MRI metrics
Description
To determine the predictive value of brain microglial inflammation on subsequent brain atrophy progression after a follow up period of two years.
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion criteria Healthy volunteers (group I, n=20) Aged 18-65 years; Able to understand the objectives and procedures of the study, and who give inform consent. Patients with relapsing-remitting MS (group II, n=15) Aged 18-65 years Clinically definite MS according to McDonald revised criteria Less than 10 year of evolution No clinical relapse during the past 3 months Able to understand the objectives and procedures of the study, and who give inform consent Patients with progressive MS (group III and IV, n=15 per group) Aged 18-65 years Clinically definite MS according to McDonald revised criteria SPMS evolving since more than 10 years for group III (n = 15). PPMS evolving since less than 10 years for group IV (n=15). Each progressive patient should have experienced a significant progression during the 2 years preceding the inclusion (with an estimated progression of the EDSS score of at least 0.5 point). No clinical relapse during the past 3 months Able to understand the objectives and procedures of the study, and who give inform consent. Exclusion criteria Any reason, which does not allow performing MRI: claustrophobia, pace-maker or intra-ocular foreign body for example. For women: pregnancy, lactation, lack of efficient contraception. At visit 2, a positive pregnancy test will lead to exclude the patient. Uncontrolled diabetes Current symptoms of severe or uncontrolled renal, hepatic, hematological, gastrointestinal pulmonary or cardiac disease. Positive HIV test Prior participation in other research protocols or clinical care in the last year such that radiation exposure would exceed the annual guidelines. Other chronic neurological disease.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bruno Stankoff
Organizational Affiliation
Assistance Publique - Hôpitaux de Paris
Official's Role
Principal Investigator
Facility Information:
Facility Name
Saint Antoine Hospital
City
Paris
ZIP/Postal Code
75012
Country
France
Facility Name
Pitie Salpetriere Hospital
City
Paris
ZIP/Postal Code
75013
Country
France

12. IPD Sharing Statement

Citations:
PubMed Identifier
36229188
Citation
Ricigliano VAG, Louapre C, Poirion E, Colombi A, Yazdan Panah A, Lazzarotto A, Morena E, Martin E, Bottlaender M, Bodini B, Seilhean D, Stankoff B. Imaging Characteristics of Choroid Plexuses in Presymptomatic Multiple Sclerosis: A Retrospective Study. Neurol Neuroimmunol Neuroinflamm. 2022 Oct 13;9(6):e200026. doi: 10.1212/NXI.0000000000200026. Print 2022 Nov.
Results Reference
derived
PubMed Identifier
28178885
Citation
Garcia-Lorenzo D, Lavisse S, Leroy C, Wimberley C, Bodini B, Remy P, Veronese M, Turkheimer F, Stankoff B, Bottlaender M. Validation of an automatic reference region extraction for the quantification of [18F]DPA-714 in dynamic brain PET studies. J Cereb Blood Flow Metab. 2018 Feb;38(2):333-346. doi: 10.1177/0271678X17692599. Epub 2017 Feb 9.
Results Reference
derived

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Imaging of Intracerebral Inflammation in MS

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