Coagulation/Complement Activation and Cerebral Hypoperfusion in Relapsing-remitting Multiple Sclerosis

Study Overview
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Brief Summary
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This is a multi-center, prospective, controlled study. MS patients (1° group: 30 patients in relapse; 2° group: 30 patients in remission) and age/sex-matched healthy controls (3° group: 30 subjects) will be enrolled in the study. Patients' disability level will be evaluated by EDSS and MSFC. Patients and controls will be tested for either coagulation/complement (C3, C4, C4a, C9, fibrinogen, factor VIII and X, D-dimer, protein C, protein S, antithrombin, factor II, aPTT, von-Willebrand factor), soluble markers of endothelial damage (thrombomodulin, Endothelial Protein C Receptor), antiphospholipid antibodies, lupus anticoagulant, complete blood count, viral serological assays or microRNA microarray. Patients will undergo dynamic susceptibility contrast-enhanced MRI using a 3.0-T scanner to evaluate CBF, CBV, MTT, lesion number and volume.

Official Title
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Coagulation/Complement Activation and Cerebral Hypoperfusion in Relapsing-remitting Multiple Sclerosis

Conditions
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Multiple Sclerosis, Relapse

Intervention / Treatment
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* Diagnostic Test: Blood samples and processing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients diagnosed with relapsing-remitting multiple sclerosis, untreated or treated with only immunomodulatory therapy, in relapse o in remission Exclusion Criteria: pregnant, with any neoplastic, hematologic, thyroid, metabolic, thrombotic or autoimmune disease, drug or alcohol addicted, treated with immunosuppressive drugs, steroids o any medication interfering with coagulation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Relapsing MS patients<br>Patients diagnosed with relapsing-remitting multiple sclerosis and in relapse, untreated or treated with only immunomodulatory therapy. | Diagnostic Test: Blood samples and processing<br>* DSC perfusion technique at 3.0-T MRI only in MS patients<br>* Other names: complement C3, C4, C4a, C9, fibrinogen, factor VIII and X, D-dimer, protein C, protein S, antithrombin, aPTT, factor II, v-Willebrand factor, thrombomodulin, Endothelial Protein C Receptor;|
| Remitting MS patients<br>Patients diagnosed with relapsing-remitting multiple sclerosis and in remission, untreated or treated with only immunomodulatory therapy. | Diagnostic Test: Blood samples and processing<br>* DSC perfusion technique at 3.0-T MRI only in MS patients<br>* Other names: complement C3, C4, C4a, C9, fibrinogen, factor VIII and X, D-dimer, protein C, protein S, antithrombin, aPTT, factor II, v-Willebrand factor, thrombomodulin, Endothelial Protein C Receptor;|
| Healthy controls<br>Age- and sex-matched healthy control subjects. | Diagnostic Test: Blood samples and processing<br>* DSC perfusion technique at 3.0-T MRI only in MS patients<br>* Other names: complement C3, C4, C4a, C9, fibrinogen, factor VIII and X, D-dimer, protein C, protein S, antithrombin, aPTT, factor II, v-Willebrand factor, thrombomodulin, Endothelial Protein C Receptor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| plasma concentration of coagulation factor | Factor VIII (%) | through study completion, an average of 1 year | 
| plasma concentration of coagulation factor | Factor X (%) | through study completion, an average of 1 year | 
| plasma concentration of coagulation factor | D-dimer (ng/ml) | through study completion, an average of 1 year | 
| plasma concentration of coagulation factor | Protein C (%) | through study completion, an average of 1 year | 
| plasma concentration of coagulation factor | Protein S (%) | through study completion, an average of 1 year | 
| plasma concentration of coagulation factor | Fibrinogen (mg/dl) | through study completion, an average of 1 year | 
| plasma concentration of coagulation factor | complement (mg/dl) | through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brain MRI hemodynamic changes at DSC 3.0-T MRI | cerebral blood flow | through study completion, an average of 1 year | 
| Brain MRI hemodynamic changes at DSC 3.0-T MRI | cerebral blood volume | through study completion, an average of 1 year | 
| Brain MRI hemodynamic changes at DSC 3.0-T MRI | mean transit time | through study completion, an average of 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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multiple sclerosis, relapse, coagulation, complement, cerebral blood flow