Prospective Randomized Endovascular Therapy in Multiple Sclerosis - PREMiSE

Study Overview
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Brief Summary
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The Departments of Neurology and Neurosurgery are conducting this research study to evaluate the safety and effectiveness of intravascular angioplasty for the treatment of venous narrowing in the treatment of Multiple Sclerosis (MS).

Official Title
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Prospective Randomized Endovascular Therapy in Multiple Sclerosis - PREMiSE

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Device: Selective Venography followed by therapeutic balloon angioplasty
* Other: Control arm


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-65 years EDSS 0-6.5 (0-5.5 in the phase II of the study) Diagnosis of relapsing MS according to the McDonald criteria (Polman et al., 2005) 1 relapse within the past 12 months or GAD positive lesion on an MRI within the past 3 months (only for phase II of the study) Be on treatment with currently FDA approved disease-modifying treatments (excluding Tysabri or steroids (within the last 30 days prior to enrollment) Evidence of ≥2 sonographic parameters of suspicious abnormal extracranial cerebral venous outflow (see Table 1 background and 1.5 section) Normal renal function: creatinine clearance level of >60 Exclusion Criteria: Relapse, disease progression and Tysabri and steroid treatment in the 30 days preceding study entry Pre-existing medical conditions known to be associated with brain pathology (e.g., neurodegenerative disorder, cerebrovascular disease, positive history of alcohol abuse, etc.) Severe peripheral chronic venous insufficiency Abnormal renal function Contrast allergy (anaphylaxis) Not accepting to undergo the endovascular treatment Peripheral Vascular Disease

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: Control arm<br>Venography and sham angioplasty | Other: Control arm<br>* Venography and sham angioplasty<br>|
| Active Comparator: Active arm<br>therapeutic balloon angioplasty | Device: Selective Venography followed by therapeutic balloon angioplasty<br>* Venography followed by therapeutic balloon angioplasty<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety | - Percent (%) of patients with Severe Adverse Events (SAE) measured at 24 hours (Immediate) and 1 month (Short term) post-surgical safety outcome in MS patients diagnosed with CCSVI that underwent therapeutic angioplasty. . The 95% confidence interval of the SAE rates for immediate and short terms will be obtained by the exact method, respectively. For Phase II study, the immediate and short term SAE rates will be analyzed, respectively, using the Fisher's exact test. | 24 hours-1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Preliminary efficacy | - Restoration of venous outflow (more than 75% of normal outflow) as measured by the combined ECD/TCD and MRV at 1 month, 3 months, 6 months, and 1 yearfollowing the angioplasty as compared to baseline as well as compared to a parallel control group of MS patients that will undergo only selective venography without balloon angioplasty (sham-angioplasty). These comparisons will be accomplished by the hierarchical linear model which takes into account the correlation within subjects. Based on the residuals, we will check the normality assumptions by the normal quantile plot and skewness. | 1 month, 3 months, 6 months, and 1 yearfollowing |