Multiple SclerosisFLUMA-SEP-TNCT03825601
PET with [18F]Flumazenil As an Index of Neurodegeneration in MS
A study testing PET with [11C]Flumazenil in people with Multiple Sclerosis and Relapsing-Remitting Multiple Sclerosis, run by Institut National de la Santé Et de la Recherche Médicale, France at 1 site in France.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Multiple Sclerosis, Relapsing-Remitting Multiple Sclerosis
- What is being tested?
- PET with [11C]Flumazenil
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 1 siteFrance
- Study dates
- 2 May 2019to 26 Aug 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Show all 19Show fewer
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
France1 site
Centre d'Investigation Clinique de Neuroscience, Groupe Hospitalier Pitié Salpêtrière, ICM, Pitié Salpêtrière
Paris, 75651
About this study
Official title: PET with [18F]Flumazenil As an Index of Neurodegeneration in MS: Sensitivity At an Early Disease Stage and Pathophysiological Meaning
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.
Read the 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.
- Being tested
- PET with [11C]Flumazenil
- Keywords
- Patients,, Multiple Sclerosis,, Relapsing-Remitting
- Medical subject headings
- Multiple Sclerosis, Multiple Sclerosis, Relapsing-Remitting
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PET with [11C]FlumazenilDiagnostic test
Also called 7T and 3T MRI
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.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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. Receives: Diagnostic Test: PET with [11C]Flumazenil |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: [0-2] MONTHS
Secondary outcomes (6)
individual maps of neurodegeneration: changes in individual mapping of Flumazenil binding in different groups
Individual mapping of Flumazenil binding changes in the grey matter of patients with MS compared to healthy controls at the voxel level
Measured: [0-2] MONTHS
volume of cortical lesions assessed on 7T MRI in different groups assessed in Cortical lesion volume
volume of cortical lesions assessed on 7T MRI in different groups assessed in Cortical lesion volume
Measured: [0-2] MONTHS
volume of white matter lesions segmented on 3T T2 sequences: white matter lesion load
volume of white matter lesions segmented on 3T T2 sequences: white matter lesion load
Measured: [0-2] MONTHS
Volume of gadolinium-enhanced white matter lesions on T1 sequence
Volume of gadolinium-enhanced white matter lesions assessed on T1 sequence
Measured: [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
Voxel wise assessment of Magnetization transfer ratio (MTR) to assess changes in the grey and in the white matter in different groups
Measured: [0-2] MONTHS
functional connectivity changes in patients
functional connectivity assessed on resting state fMRI
Measured: [0-2] MONTHS
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2019
- Study start2 May 2019
- Primary completion26 Aug 2024
- Study completion26 Aug 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by Institut National de la Santé Et de la Recherche Médicale, FranceThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Sponsor type
- Other government
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03825601
- Sponsor's protocol ID
- C16-31
- Acronym
- FLUMA-SEP-T
- Status last verified
- Mar 2025
- First submitted
- 21 Jan 2019
- Last updated
- 5 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PET with [18F]Flumazenil As an Index of Neurodegeneration in MS: Sensitivity At an Early Disease Stage and Pathophysiological Meaning
- ClinicalTrials.gov ID
- NCT03825601
- Acronym / sponsor ID
- FLUMA-SEP-T / C16-31
- Keywords
- Patients,, Multiple Sclerosis,, Relapsing-Remitting
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Institut National de la Santé Et de la Recherche Médicale, FranceOther government
- Study start
- 2 May 2019 (actual)
- Primary completion
- 26 Aug 2024 (actual)
- Study completion
- 26 Aug 2024 (actual)
- First posted
- 31 Jan 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patients with multiple sclerosis | Other | Diagnostic Test: PET with [11C]FlumazenilThe 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). |
| healthy subjects | Other | Diagnostic Test: PET with [11C]Flumazenil15 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. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (19 listed)
- Patient group:
- Healthy subjects
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PET with [11C]FlumazenilAlso: 7T and 3T MRI7T MRI sequences : TSE, T2w FLAIR GRE-T2* and DIR 3T MRI sequences: T1, T2, T1 with gadolinium, magnetization transfer, diffusion weighted, resting state fMRI. | Diagnostic test | Patients with multiple sclerosis, healthy subjects |
Primary outcome
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.
6 secondary outcomes
individual maps of neurodegeneration: changes in individual mapping of Flumazenil binding in different groups
Time frame: [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 white matter lesions segmented on 3T T2 sequences: white matter lesion load
Time frame: [0-2] MONTHS
Volume of gadolinium-enhanced white matter lesions on T1 sequence
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
Time frame: [0-2] MONTHS
functional connectivity changes in patients
Time frame: [0-2] MONTHS
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing PET with [11C]Flumazenil in people with Multiple Sclerosis and Relapsing-Remitting Multiple Sclerosis, run by Institut National de la Santé Et de la Recherche Médicale, France at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Concentration of benzodiazepine receptors (BZR) measured from 11C -Flumazenil binding in different groups (time frame: [0-2] MONTHS). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Mar 2025.