- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01567553
The Inflammatory Process and the Medical Imaging in Patients With an Inflammatory Disease of the Central Nervous System. (USPIO-CIS)
Early Neuroinflammatory Changes as a Prognostic Marker in Clinically Isolated Syndromes Patients.
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Actual)
Contacts and Locations
Study Locations
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Marseille, France, 13385
- La Timone University Hospital (APHM)
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Paris, France, 75013
- La Pitie-Salpaetriere Hospital (APHP)
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Reims, France, 51092
- MAISON BLANCHE Hospital
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Rennes, France, 35000
- Rennes University Hospital
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Toulouse, France, 31059
- Purpan Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
- 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
- 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
Exclusion Criteria:
- 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
- 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
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
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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.
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USPIO MRI scanning will be performed at :
Gadolinium MRI scanning will be performed at baseline, month 3, month 6, month 9, month 12, month 18, month 24 and month 36. |
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.
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USPIO MRI scanning will be performed at :
Gadolinium MRI scanning will be performed at baseline, month 3, month 6, month 9, month 12, month 18, month 24 and month 36. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
▪ 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
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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).
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Change from baseline in USPIO enhancing MS lesion at 12 months after the first event of the disease
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Comparison of primary outcome measures with clinical outcomes and role of USPIO
Time Frame: at 12 months after the first event of the disease
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▪ 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
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at 12 months after the first event of the disease
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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
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▪ 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))
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at 12 months after the first event of the disease
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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
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▪ 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
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Change from baseline in USPIO and/or Gadolinium enhancing MS lesions at 3 years after the first event of the disease
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: EDAN Gilles, Rennes University Hospital
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2007-005363-10
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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