Multiple Sclerosis (MS)USPIO-CISNCT01567553
The Inflammatory Process and the Medical Imaging in Patients With an Inflammatory Disease of the Central Nervous System.
An observational study of Multiple Sclerosis (MS) and Inflammatory Disease, run by Rennes University Hospital at 5 sites in France.
Trial summary
While significant progress has been made on medical imagery in recent years in the individualization of different lesions in the nervous system for demyelination, axonal loss, atrophy, little progress has been made in the specific recognition the inflammatory process. Read more about this study
- Who is it for?
- Ages 18 to 45 years
- Conditions the study is for
- Multiple Sclerosis (MS), Inflammatory Disease
- What is being tested?
- USPIO MRI - Gadolinium MRI
- How many people
- 37 participants
- Where
- 5 sitesFrance
- Study dates
- Apr 2009to Jun 2015
- Phase
- Observational
- 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 45 years
- All sexes
- No healthy volunteers
- Adult
Study population: CIS at presentation (clinically isolated syndromes) will be recruited with MRI evidence of at least two asymptomatic brain MRI lesions. The group will compromise 50 CIS patients. These CIS patients will be included within three months after first clinical presentation.
Who may be able to join
- Age between 18 and 45 years
- Patients with a first episode suggestive of MS (monofocal or multifocal)
- Presence of a first neurologic event suggestive of MS that lasted for at least 24 hours
- Patients with a spatial dissemination criteria according to the Mc Donald diagnostic criteria
- With an Expanded Disability Status Scale (EDSS) score at baseline between 0 and 5
- USPIO (SH U 555 C) injection has to be performed within 3 months after start of clinical event
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- Patients have to be in-patients for a minimum of 24 hours after the first USPIO (SH U 555 C) injection
- Patients with positive or negative USPIO-MRI during screening are included
- Patients must be compliant with study protocol
- Patients must have given their written consent to participate in this study
Who cannot join
- Any CIS patients having received steroid treatment before acquisition of the baseline USPIO MR scan
- Patients in whom any disease other than MS could explain their signs and symptoms,
- Patients with complete transverse myelitis or bilateral optic neuritis will be excluded,
- Patients who had received prior immunosuppressive or immunomodulatory treatment will be excluded.
- Patients who had received corticoids 30 days before USPIO-RMI
- Patients which cannot be in-patients for a minimum of 24 hours after the first USPIO (SH U 555 C) injection
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- Female patients without efficient contraception (oral or others) Pregnant or lactating patients
- Patients with a known allergy to iron particles and/or dextrans
- Patients having received in the past 5 months iron oxide particles preceding the MRI examination
- Patients with a past history of bronchial asthma or any other allergic disorder
- Patients with a past history for a lower threshold of seizures
- Any patient presenting with a known contra-indication for MR scanning
- Non-compliant or uncooperative patients with regard to study protocol
- Patients not having given their written consent to participate in this study
- Any patient with an accompanying systemic disease, renal disease, cardiac disease or mental disorder
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
France5 sites
La Timone University Hospital (APHM)
Marseille, 13385
La Pitie-Salpaetriere Hospital (APHP)
Paris, 75013
Maison Blanche Hospital
Reims, 51092
Rennes University Hospital
Rennes, 35000
Purpan Hospital
Toulouse, 31059
About this study
Official title: Early Neuroinflammatory Changes as a Prognostic Marker in Clinically Isolated Syndromes Patients.
While significant progress has been made on medical imagery in recent years in the individualization of different lesions in the nervous system for demyelination, axonal loss, atrophy, little progress has been made in the specific recognition the inflammatory process. Yet this point is essential since the currently available treatments have a partial impact mainly on the inflammatory component and that many uncertainties remain about the links between inflammation and tissue destruction affecting myelin and axons. The recent discovery of a macrophage cell marker in the CNS, more specific (USPIO) of inflammation gives us the opportunity to answer important questions which one can sense that this could have a significant impact on therapeutic drug monitoring of these patients. This study will involve 50 patients recruited in five French centers (Marseille, Paris, Reims, Rennes, Toulouse) from the earliest manifestations of the disease with clinical and MRI scheduled for the first 3 years of their disease.
Read the detailed description
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system affecting 60.000 persons in France and characterized by widespread inflammation, focal demyelination, and a variable degree of axonal loss. In recent years the concept of MS as an inflammatory neurodegenerative disease has been corroborated by neuropathologic and in vivo MR imaging studies. A number of MR studies show that the principal pathological substrate of permanent disability is axonal loss as detected in MR studies as global atrophy, but also regionally in the white or grey matter, and that atrophy already occurs at early stages of the disease. Though MR imaging is a powerful tool for MS in terms of diagnosis, description of the natural history of the disease and treatment monitoring, the major drawback of MRI in MS is the lack of specificity of the MR findings. Furthermore, with the advent of disease modifying drugs, there is a need for robust and specific MR markers to identify e.g. clinically isolated syndrome (CIS) patients at presentation at high risk to develop MS or a more severe disease course. An increasing body of MRI evidence corroborates that CIS show early and dynamic changes detected by MR imaging, such as global or regional brain atrophy, as a sign of progressive axonal loss, but atrophy is already a late stage sign of the disease, when tissue is lost. Considerable efforts are spent today to identify early and prognostic MR markers for high risk CIS patients.
In the current project we endeavour to study CIS patients with inflammatory disease of the central nervous system or early clinical deficit by using cell labelling MR imaging with ultra small superparamagnetic iron oxide particles (USPIO), which specifically label blood-borne macrophages, a key cell population in MS. We hypothesise that number/volume of USPIO (SH U 555 C) enhancement during the first year is a predictive marker for high risk CIS patients at presentation. This hypothesis is in line with recent findings in the animal model of MS, EAE. Secondary measures of this study will include comparison of the USPIO (SH U 555 C) findings with other highly sensitive, but non-specific MR parameters.
- Conditions
- Multiple Sclerosis (MS), Inflammatory Disease
- Being tested
- USPIO MRI - Gadolinium MRI
- Keywords
- inflammatory disease of the central nervous system, early clinical deficit, multiple sclerosis (MS)
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
USPIO MRI - Gadolinium MRIOther
USPIO MRI scanning will be performed at :
- baseline, month 3, month 6, month 9 and month 12 for patients recruited prior to the 1st of May 2010.
- baseline, month3, month 6 and month 9 for patients recruited between the 1st of May 2010 and the 31st of July 2010,
- baseline, month 3 and month 6 for patients recruited between the 1st of August 2010 and the 31st of October 2010,
- baseline and month 3 for patients recruited between the 1st of November 2010 and the 31st of January 2011,
- baseline for patients recruited between the 1st of February 2011 and the 30rd of April 2011.
Gadolinium MRI scanning will be performed at baseline, month 3, month 6, month 9, month 12, month 18, month 24 and month 36.
| Study group | Role | What they receive |
|---|---|---|
| Control group | Only unenhanced MR scanning will be performed in a control group of normal, age-matched subjects and after acceptance of the protocol by an independent ethical committee for the implication of a normal population in such an MRI research project. Receives: Other: USPIO MRI - Gadolinium MRI | |
| Experimental group | CIS at presentation (clinically isolated syndromes) will be recruited with MRI evidence of at least two asymptomatic brain MRI lesions. The group will compromise 50 CIS patients. These CIS patients will be included within three months after first clinical presentation. Receives: Other: USPIO MRI - Gadolinium MRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
▪ Change in USPIO enhancing MS lesion
USPIO enhancing MS lesion at baseline and during 12 month after the first event of the disease as a predictor for a higher risk to develop a second clinical event (time to second clinical event) in CIS patients (evidence of USPIO enhancement: yes/no; and number of USPIO lesions).
Measured: Change from baseline in USPIO enhancing MS lesion at 12 months after the first event of the disease
Secondary outcomes (3)
Comparison of primary outcome measures with clinical outcomes and role of USPIO
▪ Comparison of primary outcome measures with clinical outcomes (EDSS and conversion to MS) - and role of USPIO (SH U 555 C) as a potential biomarker to predict these two clinical outcomes
Measured: at 12 months after the first event of the disease
Relationship of USPIO (SH U 555 C) enhancing MRI lesions with other MR parameters
▪ Relationship of USPIO (SH U 555 C) enhancing MRI lesions with other MR parameters (Differently weighted MR-lesions : T2, T1, FLAIR ; MR diffusion measures, MTR ; MR atrophy measures (global and regional atrophy))
Measured: at 12 months after the first event of the disease
Change in USPIO and/or Gadolinium enhancing MS lesions (primary outcome measure)
▪ USPIO and/or Gadolinium enhancing MS lesions as a predictor for a higher risk to develop a second clinical event (time to second clinical event) in CIS patients (evidence of USPIO or Gd enhancement: yes/no; and number of USPIO and/or Gd lesions)at 3 years after the first event of the disease
Measured: Change from baseline in USPIO and/or Gadolinium enhancing MS lesions at 3 years after the first event of the disease
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Mar 2012 (estimated)
- Study startApr 2009
- Primary completionJun 2014
- Study completionJun 2015
Why it stopped: terminated ( Halted prematurely,expiration of investigationnal product)
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 Sclerosis (MS)Studies of the same condition, open and under way.
- More trials run by Rennes University HospitalThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rennes University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Bayer
- Responsible party
- Sponsor
- Investigators
- EDAN Gilles, Principal investigator, Rennes University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01567553
- Sponsor's protocol ID
- 2007-005363-10
- Acronym
- USPIO-CIS
- Status last verified
- Jan 2015
- First submitted
- 24 Feb 2012
- Last updated
- 28 Oct 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Crimi A, Commowick O, Maarouf A, Ferre JC, Bannier E, Tourbah A, Berry I, Ranjeva JP, Edan G, Barillot C. Predictive value of imaging markers at multiple sclerosis disease onset based on gadolinium- and USPIO-enhanced MRI and machine learning. PLoS One. 2014 Apr 1;9(4):e93024. doi: 10.1371/journal.pone.0093024. eCollection 2014.
PubMed 24691080
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Neuroinflammatory Changes as a Prognostic Marker in Clinically Isolated Syndromes Patients.
- ClinicalTrials.gov ID
- NCT01567553
- Acronym / sponsor ID
- USPIO-CIS / 2007-005363-10
- Conditions
- Multiple Sclerosis (MS), Inflammatory Disease
- Keywords
- inflammatory disease of the central nervous system, early clinical deficit, multiple sclerosis (MS)
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: terminated ( Halted prematurely,expiration of investigationnal product)
- Enrolment
- 37 participants (actual)
- Lead sponsor
- Rennes University HospitalUniversity, hospital or other
- Collaborators
- Bayer
- Study start
- Apr 2009
- Primary completion
- Jun 2014 (actual)
- Study completion
- Jun 2015 (actual)
- First posted
- 30 Mar 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.
While significant progress has been made on medical imagery in recent years in the individualization of different lesions in the nervous system for demyelination, axonal loss, atrophy, little progress has been made in the specific recognition the inflammatory process. Yet this point is essential since the currently available treatments have a partial impact mainly on the inflammatory component and that many uncertainties remain about the links between inflammation and tissue destruction affecting myelin and axons. The recent discovery of a macrophage cell marker in the CNS, more specific (USPIO) of inflammation gives us the opportunity to answer important questions which one can sense that this could have a significant impact on therapeutic drug monitoring of these patients. This study will involve 50 patients recruited in five French centers (Marseille, Paris, Reims, Rennes, Toulouse) from the earliest manifestations of the disease with clinical and MRI scheduled for the first 3 years of their disease.
Detailed description
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system affecting 60.000 persons in France and characterized by widespread inflammation, focal demyelination, and a variable degree of axonal loss. In recent years the concept of MS as an inflammatory neurodegenerative disease has been corroborated by neuropathologic and in vivo MR imaging studies. A number of MR studies show that the principal pathological substrate of permanent disability is axonal loss as detected in MR studies as global atrophy, but also regionally in the white or grey matter, and that atrophy already occurs at early stages of the disease. Though MR imaging is a powerful tool for MS in terms of diagnosis, description of the natural history of the disease and treatment monitoring, the major drawback of MRI in MS is the lack of specificity of the MR findings. Furthermore, with the advent of disease modifying drugs, there is a need for robust and specific MR markers to identify e.g. clinically isolated syndrome (CIS) patients at presentation at high risk to develop MS or a more severe disease course. An increasing body of MRI evidence corroborates that CIS show early and dynamic changes detected by MR imaging, such as global or regional brain atrophy, as a sign of progressive axonal loss, but atrophy is already a late stage sign of the disease, when tissue is lost. Considerable efforts are spent today to identify early and prognostic MR markers for high risk CIS patients.
In the current project we endeavour to study CIS patients with inflammatory disease of the central nervous system or early clinical deficit by using cell labelling MR imaging with ultra small superparamagnetic iron oxide particles (USPIO), which specifically label blood-borne macrophages, a key cell population in MS. We hypothesise that number/volume of USPIO (SH U 555 C) enhancement during the first year is a predictive marker for high risk CIS patients at presentation. This hypothesis is in line with recent findings in the animal model of MS, EAE. Secondary measures of this study will include comparison of the USPIO (SH U 555 C) findings with other highly sensitive, but non-specific MR parameters.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control group | – | Other: USPIO MRI - Gadolinium MRIOnly unenhanced MR scanning will be performed in a control group of normal, age-matched subjects and after acceptance of the protocol by an independent ethical committee for the implication of a normal population in such an MRI research project. |
| Experimental group | – | Other: USPIO MRI - Gadolinium MRICIS at presentation (clinically isolated syndromes) will be recruited with MRI evidence of at least two asymptomatic brain MRI lesions. The group will compromise 50 CIS patients. These CIS patients will be included within three months after first clinical presentation. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- CIS at presentation (clinically isolated syndromes) will be recruited with MRI evidence of at least two asymptomatic brain MRI lesions. The group will compromise 50 CIS patients. These CIS patients will be included within three months after first clinical presentation.
Key inclusion criteria (10 listed)
- Age between 18 and 45 years
- Patients with a first episode suggestive of MS (monofocal or multifocal)
- Presence of a first neurologic event suggestive of MS that lasted for at least 24 hours
- Patients with a spatial dissemination criteria according to the Mc Donald diagnostic criteria
- With an Expanded Disability Status Scale (EDSS) score at baseline between 0 and 5
Key exclusion criteria (15 listed)
- Any CIS patients having received steroid treatment before acquisition of the baseline USPIO MR scan
- Patients in whom any disease other than MS could explain their signs and symptoms,
- Patients with complete transverse myelitis or bilateral optic neuritis will be excluded,
- Patients who had received prior immunosuppressive or immunomodulatory treatment will be excluded.
- Patients who had received corticoids 30 days before USPIO-RMI
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 |
|---|---|---|
| USPIO MRI - Gadolinium MRIUSPIO MRI scanning will be performed at : * baseline, month 3, month 6, month 9 and month 12 for patients recruited prior to the 1st of May 2010. * baseline, month3, month 6 and month 9 for patients recruited between the 1st of May 2010 and the 31st of July 2010, * baseline, month 3 and month 6 for patients recruited between the 1st of August 2010 and the 31st of October 2010, * baseline and month 3 for patients recruited between the 1st of November 2010 and the 31st of January 2011, * baseline for patients recruited between the 1st of February 2011 and the 30rd of April 2011. Gadolinium MRI scanning will be performed at baseline, month 3, month 6, month 9, month 12, month 18, month 24 and month 36. | Other | Control group, Experimental group |
Primary outcome
▪ Change in USPIO enhancing MS lesion
Time frame: Change from baseline in USPIO enhancing MS lesion at 12 months after the first event of the disease
USPIO enhancing MS lesion at baseline and during 12 month after the first event of the disease as a predictor for a higher risk to develop a second clinical event (time to second clinical event) in CIS patients (evidence of USPIO enhancement: yes/no; and number of USPIO lesions).
3 secondary outcomes
Comparison of primary outcome measures with clinical outcomes and role of USPIO
Time frame: at 12 months after the first event of the disease
Relationship of USPIO (SH U 555 C) enhancing MRI lesions with other MR parameters
Time frame: at 12 months after the first event of the disease
Change in USPIO and/or Gadolinium enhancing MS lesions (primary outcome measure)
Time frame: Change from baseline in USPIO and/or Gadolinium enhancing MS lesions at 3 years after the first event of the disease
Results and safety
The study was stopped early (reason given: terminated ( Halted prematurely,expiration of investigationnal product)). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2015.
- Results publication: PubMed 24691080Crimi A, Commowick O, Maarouf A, Ferre JC, Bannier E, Tourbah A, Berry I, Ranjeva JP, Edan G, Barillot C. Predictive value of imaging markers at multiple sclerosis disease onset based on gadolinium- and USPIO-enhanced MRI and machine learning. PLoS One. 2014 Apr 1;9(4):e93024. doi: 10.1371/journal.pone.0093024. eCollection 2014.
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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.
EDAN Gilles principal investigator
Rennes University Hospital
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Multiple Sclerosis (MS) and Inflammatory Disease, run by Rennes University Hospital at 5 sites 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 10 inclusion and 15 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: stopped early, as of the sponsor's last update on 28 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites 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 was stopped early (reason given: terminated ( Halted prematurely,expiration of investigationnal product)). 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?
▪ Change in USPIO enhancing MS lesion (time frame: Change from baseline in USPIO enhancing MS lesion at 12 months after the first event of the disease). 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 NCT01567553, 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 28 Oct 2015.