- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03825601
PET With [18F]Flumazenil as an Index of Neurodegeneration in MS (FLUMA-SEP-T)
PET With [18F]Flumazenil as an Index of Neurodegeneration in MS: Sensitivity at an Early Disease Stage and Pathophysiological Meaning
Study Overview
Status
Intervention / Treatment
Detailed Description
The investigators have recently shown that PET (Tomographie par Émission de Positrons) with [11C]Flumazenil ([11C]FMZ), that binds to the benzodiazepine site of GABA-A receptors, allowed to quantify and map neuronal damage in MS patients.
In the present project, the investigators will assess neuronal damage in MS using PET with [18F]Flumazenil ([18F]FMZ), at the early phase of either relapsing or primary progressive MS, and investigate the pathophysiological meaning of this neuronal damage by combining PET with Flumazenil with MRI at 7T and 3T.
The main objective will be to quantify and map [18F]FMZ binding changes in the grey matter of MS patients compared to controls, both at the group and the individual level. Secondary and exploratory objectives will be to investigate the relationship between Flumazenil binding changes and: i) cortical demyelinating lesions identified by several 7T MRI sequences ; ii) dendritic arborisation assessed by 3T DWI; ii) available MRI metrics obtained on a clinical 3T scan (grey matter atrophy MTR modifications, resting state connectivity); iv) clinical metrics.
This study will develop and assess a new imaging biomarker that has the potential to be used as an index of neurodegeneration in MS.
Study Type
Enrollment (Anticipated)
Phase
- Not Applicable
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
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
- No current benzodiazepine or other GABAA-interacting drug (that have to be stopped 15 days before inclusion)
- 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
- Having signed the written consent form
- No concurrent benzodiazepine or other GABAA-interacting drug treatment (that have to be stopped 15 days before inclusion)
- Accept to be informed of any incidental finding on imaging acquisitions
Exclusion Criteria:
- 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.
- For women: pregnancy, lactation, lack of efficient contraception. A positive pregnancy test conducted at visit 2 will lead to the immediate exclusion of the subject.
- Current symptoms of severe or uncontrolled renal, hepatic, hematological, gastrointestinal pulmonary or cardiac disease.
- Radiation exposure during the last year before inclusion due to prior participations to other research protocols
- Other chronic neurological diseases.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: DIAGNOSTIC
- Allocation: NON_RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
OTHER: Patients with multiple sclerosis
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).
|
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.
Other Names:
|
OTHER: healthy subjects
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.
|
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.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Concentration of benzodiazepine receptors (BZR) measured from 11C -Flumazenil binding in different groups
Time Frame: [0-2] MONTHS
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
individual maps of neurodegeneration: changes in individual mapping of Flumazenil binding in different groups
Time Frame: [0-2] MONTHS
|
Individual mapping of Flumazenil binding changes in the grey matter of patients with MS compared to healthy controls at the voxel level
|
[0-2] MONTHS
|
volume of cortical lesions assessed on 7T MRI in different groups assessed in Cortical lesion volume
Time Frame: [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
Time Frame: [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
Time Frame: [0-2] MONTHS
|
Volume of gadolinium-enhanced white matter lesions assessed 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
Time Frame: [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
|
functional connectivity changes in patients
Time Frame: [0-2] MONTHS
|
functional connectivity assessed on resting state fMRI
|
[0-2] MONTHS
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (ANTICIPATED)
Primary Completion (ANTICIPATED)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Nervous System Diseases
- Immune System Diseases
- Demyelinating Autoimmune Diseases, CNS
- Autoimmune Diseases of the Nervous System
- Demyelinating Diseases
- Autoimmune Diseases
- Multiple Sclerosis
- Sclerosis
- Multiple Sclerosis, Relapsing-Remitting
- Nerve Degeneration
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Protective Agents
- GABA Modulators
- GABA Agents
- Antidotes
- Flumazenil
Other Study ID Numbers
- C16-31
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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