PET with [18F]Flumazenil As an Index of Neurodegeneration in MS

NCT03825601 | Completed

• 1 other identifier: C16-31
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

Beyond white matter pathology, grey matter damage is considered as a key player in disability onset and progression in Multiple Sclerosis (MS). The underlying substratum of grey matter damage is complex and pluriform, ranging from cortical demyelinating lesions, synapse and dendrite disappearance to neuronal cell death. Current Magnetic Resonance Imaging MRI techniques fail to fully assess and quantify grey matter pathology in this disease. The development of a quantitative marker of neurodegeneration for MS patients would allow: (i) to better understand the pathophysiological mechanisms underlying the distinct forms of MS; (ii) to stratify patients according to their prognosis; and (iii) to evaluate new therapies aimed at promoting neuroprotection. would allow to better understand the mechanisms underlying the distinct forms of MS, to stratify patients according to their prognosis, and to evaluate new therapies aimed at promoting neuroprotection.

Conditions

Multiple Sclerosis; Relapsing-Remitting Multiple Sclerosis

Keywords

Patients,; Multiple Sclerosis,; Relapsing-Remitting

Outcome Measures

Primary Outcomes (1)

• Concentration of benzodiazepine receptors (BZR) measured from 11C -Flumazenil binding in different groups

  11C -Flumazenil binding in the grey matter : Concentration of benzodiazepine receptors (BZR) measured from 11C -Flumazenil binding kinetic analysis, and expressed as a Bmax estimation, in the cortex and deep grey matter of subjects.

  [0-2] MONTHS

Secondary Outcomes (6)

• individual maps of neurodegeneration: changes in individual mapping of Flumazenil binding in different groups

  [0-2] MONTHS

• volume of cortical lesions assessed on 7T MRI in different groups assessed in Cortical lesion volume

  [0-2] MONTHS

• volume of white matter lesions segmented on 3T T2 sequences: white matter lesion load

  [0-2] MONTHS

• Volume of gadolinium-enhanced white matter lesions on T1 sequence

  [0-2] MONTHS

• Voxel wise assessment of Magnetization transfer ratio (MTR) to assess changes in the grey and in the white matter in different groups

  [0-2] MONTHS

Study Arms (2)

Patients with multiple sclerosis

OTHER

The multiple sclerosis group (n=30) will be subdivided in two subgroups: 15 patients with a relapsing remmitting MS (RRMS), and 15 patients with a primary progressive MS (PPMS).

Diagnostic Test: PET with [11C]Flumazenil

healthy subjects

OTHER

15 healthy subjects will be included. Among them 7 to 8 subjects will be matched for age and gender with the RRMS subgroup, and 7 to 8 will be matched for age and gender with the PPMS subgroup.

Diagnostic Test: PET with [11C]Flumazenil

Interventions

PET with [11C]Flumazenil DIAGNOSTIC_TEST

7T MRI sequences : TSE, T2w FLAIR GRE-T2\* and DIR 3T MRI sequences: T1, T2, T1 with gadolinium, magnetization transfer, diffusion weighted, resting state fMRI.

Also known as: 7T and 3T MRI

Patients with multiple sclerosis; healthy subjects

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Patient group:
• Aged 18-55 years old
• Diagnosis of RRMS or PPMS according to the 2010 Mc Donald criteria
• Disease duration \< 10 years
• Able to understand the study objective and procedure
• Efficient contraception for women of potential child-bearing
• Inscription to the national health care system
• Having signed the written consent form
• Accept to be informed of any incidental finding on imaging acquisitions
• Healthy subjects
• Aged 18-55 years old
• No evolutive pathology
• Able to understand the study objective and procedure
• Efficient contraception for women of potential child-bearing
• Inscription to the national health care system

You may not qualify if:

• Any reason, which does not allow to perform MRI, including claustrophobia, the implant of a pace-maker or the presence of an intra-ocular foreign body.
• Current symptoms of severe or uncontrolled renal, hepatic, hematological, gastrointestinal pulmonary or cardiac disease.
• Other chronic neurological diseases.

Sponsors & Collaborators

• Institut National de la Santé Et de la Recherche Médicale, France: lead

Study Sites (1)

Centre d'Investigation Clinique de Neuroscience, Groupe Hospitalier Pitié Salpêtrière, ICM, Pitié Salpêtrière

Paris, 75651, France

Location

MeSH Terms

Conditions

Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 21, 2019
• First Posted: January 31, 2019
• Study Start: May 2, 2019
• Primary Completion: August 26, 2024
• Study Completion: August 26, 2024
• Last Updated: March 5, 2025

Record last verified: 2025-03

Locations

FR (1)