BRAVE-DREAMS (BRAin VEnous DRainage Exploited Against Multiple Sclerosis)

Study Overview
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Brief Summary
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To assess in a double blinded randomized control trial (RCT) study design safety and effectiveness of balloon angioplasty of the main extracranial and extravertebral veins in multiple sclerosis (MS) associated to chronic cerebrospinal venous insufficiency (CCSVI). Mean follow-up 1 year. 5-8 Italian centres 360 relapsing remitting (RR) MS patients will be randomized, with expanded disability disease scale (EDSS) ranging 2-5.5, age 18-65.

Detailed Description
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Safety will be assessed by measuring serious and minor adverse effects related to treatment. Effectiveness will be assessed by measuring 2 primary endpoints: Clinical parameters will be expressed in an integrated functional measure leading to the score, respectively, of improved, stable, worsened. Functional assessment is performed by tools permitting a quantification and will be made by a team of independent assessors. Clinical instrumental evaluation will be performed at baseline, and subsequently on 3 months basis. The outcome parameters leading to the composite functional measure are instrumental parameters, less assessor dependent, singularly validated for measuring the disability in MS. They are the followings: A) Dynamic Balance Assessment: Balance Master Limits of Stability (LOS). In static platform, swinging to reach the set position of center of pressure. B) Walking Function: The subject walks spontaneously for 10 meters with chronometric measure of time counting the number of steps. The test calculates the walk ratio i.e. ratio between length and step frequency. C) Manual dexterity. Box & Block test, moving wooden cubes. D) Sphincter control: Post-voiding residual by ultrasounds. F) Visual acuity: Low-contrast visual acuity Sloan Letter Chart. Magnetic Resonance Imaging (MRI) outcome measures: T1Gad active lesion.T2 lesion volume MRI evaluation at baseline, 6, 12 months. Secondary endpoints are: EDSS, chronic fatigue, cognitive function, rate of restenosis, annualized relapse rate.

Official Title
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Randomized Multi-centered Study for Evaluating the Efficacy and Safety of Angioplastic Surgery of the Extracranial Veins in the Treatment of Multiple Sclerosis. Studio Randomizzato Multicentrico Per la Valutazione Dell'Efficacia e Sicurezza Dell'Intervento di Disostruzione Delle Vene Extracraniche Nel Trattamento Della Sclerosi Multipla

Conditions
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Multiple Sclerosis, Venous Insufficiency

Intervention / Treatment
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* Procedure: Venous PTA
* Other: Catheter Venography


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients affected by CCSVI associated with MS relapsing-remitting and\or secondary progressive 18-65 years old EDSS 2-5 disease duration < 10y No relapse in the 30 days preceding the procedure clinical stability in the last 6 months with disease mod. treatments Patients under the best available therapy Exclusion Criteria: patients previously treated for CCSVI or inserted in other clinical trials in the last 3 months under treatment with natalizumab pregnant or refusing to adopt contraception presence of significant comorbidities alcool-drug abuse thrombophilia contraindication to MR

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>The patients will undergo PTA of the extracranial cerebral veins | Procedure: Venous PTA<br>* PTA of the internal jugular and/or azygous vein<br>|
| Sham Comparator: Controls<br>The patients will undergo sham procedure | Other: Catheter Venography<br>* The patients will undergo catheter venography but not PTA<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical parameters in an integrated functional score | Five neurological parameters will be measured by the means of proper validated tools along 1 year of follow-up. The evaluation leads to a score, respectively expressed as improved, stable, fluctuant, worsened. | Baseline; 12 months | 
| MRI outcome measures: T1Gad active lesion.T2 lesion volume MRI evaluation. | Standard MRI parameters will be assessed by the means of a blinded centre of lecture. Outcome measurement will be performed at baseline, 6 months and at 1 year follow-up. | Baseline; 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EDSS | EDSS will be assessed along 1 year follow-up. | Baseline; 12 months | 
| Chronic fatigue | This highly disabling symptom completely orphan of effective therapy will be measured by M-FIS (Modified-Fatigue Impact Scale). | Baseline; 12 months | 
| Cognitive function | Cognitive functions will be measured by the means of MoCA mental state questionnaire. | Baseline; 12 months | 
| Annualized relapse rate | In the sub population affected by the RR clinical form the number of relapse will be assessed. | Baseline; 12 months | 
| Patency rate | The rate of successful PTA will be assessed by the means of postoperative Doppler sonography. | Baseline; 12 months | 
| Emotional status | Anxiety and Depression Scale for use with multiple sclerosis patients will be administered. | Baseline; 1 year | 
| Memory and cognition | The assessment will be performed by the means of PASAT - Paced Auditory Serial Addition Test | Baseline; 1 year | 
| Overactive Bladder | Overactive Bladder symptom will be measured by the means of validated Overactive Bladder Questionnaire-b. | Baseline; 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple sclerosis, Chronic cerebrospinal venous insufficiency, Percutaneous Transluminal Angioplasty (PTA), Internal jugular vein, Azygous vein