Multiple SclerosisFlumatep_2NCT01651520
Prognosis Value of the Neuronal Damage in Early Multiple Sclerosis
A study testing PET with 11C-Flumazenil in people with Multiple Sclerosis, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
In this study the investigators will use PET and 11C-Flumazenil to visualize and quantify neuronal injury in the cortex and the deep gray matter of Multiple Sclerosis patients at an early stage. The investigators will follow up patients to determine the prognostic value of this neuronal injury. 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
- What is being tested?
- PET with 11C-Flumazenil
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteFrance
- Study dates
- Jun 2013to Jun 2019
- 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
- Four groups of subjects will be included:
- patients with a RRMS evolving since less than 5 years (revised Mc Donald criteria, n=20);
- patients with a RRMS evolving since more than 5 years and less than 10 years (n=20);
- patients with a primary progressive MS (PPMS) evolving since less than 10 years (n=20);
- Healthy volunteers matched for age and sex (2/3 matched with RRMS patients; 1/3 matched with PPMS patients).
Who cannot join
- Lack of social insurance
- Pregnancy
- Age > 55
- Therapy with benzodiazepine
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Prognosis Value of the Neuronal Damage Detected by Positrons Emission Tomography (PET) With 11C-Flumazenil in Early Multiple Sclerosis.
In this study the investigators will use PET and 11C-Flumazenil to visualize and quantify neuronal injury in the cortex and the deep gray matter of Multiple Sclerosis patients at an early stage. The investigators will follow up patients to determine the prognostic value of this neuronal injury.
Read the detailed description
It is now well admitted that multiple sclerosis (MS), which is an inflammatory demyelinating disease of the central nervous system (CNS) is not restricted to white matter, but also involves grey matter, either the cortex or the deep grey matter. The progression of grey matter atrophy measured by MRI during disease course represents an interesting prognosis marker for long term progression, but this marker lack sensitivity and is hard to interpret at the individual level.
In the EAE animal models, an early neuronal damage has been described, characterized both by a synaptic and dendritic loss and by a neuronal apoptosis.
These data strongly suggest that the occurrence of an early neuronal damage during MS course could represent a major prognosis marker. Therefore there is a crucial need for the development of imaging techniques, aimed at visualizing and quantifying neuronal damage in early MS. To date MRI techniques are not able to specifically assess neuronal pathology in vivo.
In this prospective project we will determine the chronology of appearance and the prognosis value of the neuronal damage measured by PET with 11C-Flumazenil, concerning further grey matter atrophy progression and disability progression among a cohort of MS patients with recent onset.
Four groups of subjects will be included: i) patients with a RRMS evolving since less than 5 years (revised Mc Donald criteria, n=20); ii) patients with a RRMS evolving since more than 5 years and less than 10 years (n=20); iii) patients with a primary progressive MS (PPMS) evolving since less than 10 years (n=20); iv) Healthy volunteers matched for age and sex (2/3 matched with RRMS patients; 1/3 matched with PPMS patients).
Each subject will pass a neurologic examination, a neuropsychological testing, a first PET examination with 11C-Flumazenil, a multimodal MRI, with conventional sequences (3DT1, 3D T2 and FLAIR, pre and post contrast T1) and non conventional sequences (MTR, DTI, protonic spectroscopy).
All patients will be followed prospectively with one visit/year consisting in clinical neurological, and neuropsychological evaluations as well as multimodal MRI.
For healthy volunteers a second PET 11C-Flumazenil will also be performed to assess reproducibility and evolution (50% after 1 month, 50% after 1 year).
This study will allow to assess on a larger sample followed prospectively (5 years) the prognosis value of abnormalities detected and quantified by PET with 11C-Flumazenil on further grey matter atrophy progression on MRI and disability progression (EDSS, MSFC, cognitive status). It will also precise the chronology of appearance and the evolution of neuronal damage in MS, and determine the reproducibility of this technique. Results should provide a new and more efficient prognosis marker for early MS.
- Conditions
- Multiple Sclerosis
- Being tested
- PET with 11C-Flumazenil
- Keywords
- Neurodegeneration, Disability, Cognition, Prognosis
- Medical subject headings
- Multiple Sclerosis, Nerve Degeneration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PET with 11C-FlumazenilDrug
PET with 11C-Flumazenil.
| Study group | Role | What they receive |
|---|---|---|
| Relapsing patients < 5 years | Experimental | Relapsing patients < 5 years Receives: Drug: PET with 11C-Flumazenil |
| relapsing patients < 10 years | Experimental | relapsing patients < 10 years Receives: Drug: PET with 11C-Flumazenil |
| primary progressive patients < 10 years | Experimental | primary progressive patients < 10 years Receives: Drug: PET with 11C-Flumazenil |
| healthy volunteers | Other | healthy volunteers Receives: Drug: PET with 11C-Flumazenil |
What is being measured
The primary outcome is the main question the study is designed to answer.
neuronal imaging
Prognosis value of the neuronal imaging on 2 years evolution (atrophy and EDSS)
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2012 (estimated)
- Study startJun 2013
- Primary completionJun 2019 (estimated)
- Study completionJun 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Bruno Stankoff, MD, PhD, Principal investigator, APHP
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01651520
- Sponsor's protocol ID
- IDRCB 2011-A00836-35
- Other IDs
- P100126
- Acronym
- Flumatep_2
- Status last verified
- Aug 2017
- First submitted
- 25 Jul 2012
- Last updated
- 16 Aug 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 36229188
Study at a glance
From the registry record, last updated by the sponsor on 16 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prognosis Value of the Neuronal Damage Detected by Positrons Emission Tomography (PET) With 11C-Flumazenil in Early Multiple Sclerosis.
- ClinicalTrials.gov ID
- NCT01651520
- Acronym / sponsor ID
- Flumatep_2 / IDRCB 2011-A00836-35
- Conditions
- Multiple Sclerosis
- Keywords
- Neurodegeneration, Disability, Cognition, Prognosis
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Jun 2013 (actual)
- Primary completion
- Jun 2019 (estimated)
- Study completion
- Jun 2019 (estimated)
- First posted
- 27 Jul 2012 (estimated)
- 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.
In this study the investigators will use PET and 11C-Flumazenil to visualize and quantify neuronal injury in the cortex and the deep gray matter of Multiple Sclerosis patients at an early stage. The investigators will follow up patients to determine the prognostic value of this neuronal injury.
Detailed description
It is now well admitted that multiple sclerosis (MS), which is an inflammatory demyelinating disease of the central nervous system (CNS) is not restricted to white matter, but also involves grey matter, either the cortex or the deep grey matter. The progression of grey matter atrophy measured by MRI during disease course represents an interesting prognosis marker for long term progression, but this marker lack sensitivity and is hard to interpret at the individual level.
In the EAE animal models, an early neuronal damage has been described, characterized both by a synaptic and dendritic loss and by a neuronal apoptosis.
These data strongly suggest that the occurrence of an early neuronal damage during MS course could represent a major prognosis marker. Therefore there is a crucial need for the development of imaging techniques, aimed at visualizing and quantifying neuronal damage in early MS. To date MRI techniques are not able to specifically assess neuronal pathology in vivo.
In this prospective project we will determine the chronology of appearance and the prognosis value of the neuronal damage measured by PET with 11C-Flumazenil, concerning further grey matter atrophy progression and disability progression among a cohort of MS patients with recent onset.
Four groups of subjects will be included: i) patients with a RRMS evolving since less than 5 years (revised Mc Donald criteria, n=20); ii) patients with a RRMS evolving since more than 5 years and less than 10 years (n=20); iii) patients with a primary progressive MS (PPMS) evolving since less than 10 years (n=20); iv) Healthy volunteers matched for age and sex (2/3 matched with RRMS patients; 1/3 matched with PPMS patients).
Each subject will pass a neurologic examination, a neuropsychological testing, a first PET examination with 11C-Flumazenil, a multimodal MRI, with conventional sequences (3DT1, 3D T2 and FLAIR, pre and post contrast T1) and non conventional sequences (MTR, DTI, protonic spectroscopy).
All patients will be followed prospectively with one visit/year consisting in clinical neurological, and neuropsychological evaluations as well as multimodal MRI.
For healthy volunteers a second PET 11C-Flumazenil will also be performed to assess reproducibility and evolution (50% after 1 month, 50% after 1 year).
This study will allow to assess on a larger sample followed prospectively (5 years) the prognosis value of abnormalities detected and quantified by PET with 11C-Flumazenil on further grey matter atrophy progression on MRI and disability progression (EDSS, MSFC, cognitive status). It will also precise the chronology of appearance and the evolution of neuronal damage in MS, and determine the reproducibility of this technique. Results should provide a new and more efficient prognosis marker for early MS.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Relapsing patients < 5 years | Experimental | Drug: PET with 11C-FlumazenilRelapsing patients < 5 years |
| relapsing patients < 10 years | Experimental | Drug: PET with 11C-Flumazenilrelapsing patients < 10 years |
| primary progressive patients < 10 years | Experimental | Drug: PET with 11C-Flumazenilprimary progressive patients < 10 years |
| healthy volunteers | Other | Drug: PET with 11C-Flumazenilhealthy volunteers |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- patients with a RRMS evolving since less than 5 years (revised Mc Donald criteria, n=20);
- patients with a RRMS evolving since more than 5 years and less than 10 years (n=20);
- patients with a primary progressive MS (PPMS) evolving since less than 10 years (n=20);
- Healthy volunteers matched for age and sex (2/3 matched with RRMS patients; 1/3 matched with PPMS patients).
Key exclusion criteria (4 listed)
- Lack of social insurance
- Pregnancy
- Age > 55
- Therapy with benzodiazepine
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-FlumazenilPET with 11C-Flumazenil. | Drug | Relapsing patients < 5 years, healthy volunteers, primary progressive patients < 10 years, relapsing patients < 10 years |
Primary outcome
neuronal imaging
Time frame: 2 years
Prognosis value of the neuronal imaging on 2 years evolution (atrophy and EDSS)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Aug 2017.
- Derived from this study: PubMed 36229188Ricigliano 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.
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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.
Bruno Stankoff, MD, PhD principal investigator
APHP
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, run by Assistance Publique - Hôpitaux de Paris 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 5 inclusion and 4 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: status not confirmed, as of the sponsor's last update on 16 Aug 2017. 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?
Results are not available in the source record.
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?
neuronal imaging (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01651520, which also lists 1 linked publication.
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 16 Aug 2017.