Imaging of Intracerebral Inflammation in MS

NCT02305264 | Completed DMC

• 1 other identifier: P091001
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 2

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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

  D0

Secondary Outcomes (4)

• Binding potential of 18F-DPA-714 in segmented brain regions

  D0

• Binding potential of 18F-DPA-714 in subgroups of MS patients

  D0

• Predictive value of PET 18F-DPA-714 BP on neurological clinical metrics

  2 years

• Predictive value of PET 18F-DPA-714 BP on MRI metrics

  2 years

Study Arms (1)

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

EXPERIMENTAL

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.

Drug: 18F-DPA-714 and 18F-FDG

Interventions

18F-DPA-714 and 18F-FDG DRUG

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.

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

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• No clinical relapse during the past 3 months

You may not qualify if:

• 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.

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (2)

Saint Antoine Hospital

Paris, 75012, France

Location

Pitie Salpetriere Hospital

Paris, 75013, France

Location

Related Publications (3)

• Peyronneau MA, Kuhnast B, Nguyen DL, Jego B, Sayet G, Caille F, Lavisse S, Gervais P, Stankoff B, Sarazin M, Remy P, Bouilleret V, Leroy C, Bottlaender M. [18F]DPA-714: Effect of co-medications, age, sex, BMI and TSPO polymorphism on the human plasma input function. Eur J Nucl Med Mol Imaging. 2023 Sep;50(11):3251-3264. doi: 10.1007/s00259-023-06286-1. Epub 2023 Jun 9.

  PMID: 37291448 DERIVED

• 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.

  PMID: 36229188 DERIVED

• 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.

  PMID: 28178885 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis, Chronic Progressive

Interventions

Fluorodeoxyglucose F18

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Deoxyglucose; Deoxy Sugars; Carbohydrates

Study Officials

• Bruno Stankoff

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2013
• First Posted: December 2, 2014
• Study Start: March 19, 2012
• Primary Completion: September 10, 2018
• Study Completion: September 10, 2018
• Last Updated: September 16, 2022

Record last verified: 2022-09

Locations

FR (2)