BRAVE-DREAMS (BRAin VEnous DRainage Exploited Against Multiple Sclerosis)
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. 10-20 Italian centres 445 relapsing remitting (RR)+ 234 secondary progressive (SP), overall 679 MS patients will be randomized, with expanded disability disease scale (EDSS) ranging 2-5.5, age 18-65.
Procedure: Venous PTA
Other: Catheter Venography
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||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|
- Clinical parameters in an integrated functional score [ Time Frame: Baseline; 12 months ] [ Designated as safety issue: Yes ]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.
- MRI outcome measures: T1Gad active lesion.T2 lesion volume MRI evaluation. [ Time Frame: Baseline; 12 months ] [ Designated as safety issue: Yes ]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.
- EDSS [ Time Frame: Baseline; 12 months ] [ Designated as safety issue: No ]EDSS will be assessed along 1 year follow-up.
- Chronic fatigue [ Time Frame: Baseline; 12 months ] [ Designated as safety issue: No ]This highly disabling symptom completely orphan of effective therapy will be measured by M-FIS (Modified-Fatigue Impact Scale).
- Cognitive function [ Time Frame: Baseline; 12 months ] [ Designated as safety issue: Yes ]Cognitive functions will be measured by the means of MoCA mental state questionnaire.
- Annualized relapse rate [ Time Frame: Baseline; 12 months ] [ Designated as safety issue: No ]In the sub population affected by the RR clinical form the number of relapse will be assessed.
- Patency rate [ Time Frame: Baseline; 12 months ] [ Designated as safety issue: No ]The rate of successful PTA will be assessed by the means of postoperative Doppler sonography.
- Emotional status [ Time Frame: Baseline; 1 year ] [ Designated as safety issue: No ]Anxiety and Depression Scale for use with multiple sclerosis patients will be administered.
- Memory and cognition [ Time Frame: Baseline; 1 year ] [ Designated as safety issue: No ]The assessment will be performed by the means of PASAT - Paced Auditory Serial Addition Test
- Overactive Bladder [ Time Frame: Baseline; 1 year ] [ Designated as safety issue: No ]Overactive Bladder symptom will be measured by the means of validated Overactive Bladder Questionnaire-b.
|Study Start Date:||August 2012|
|Estimated Study Completion Date:||August 2014|
|Estimated Primary Completion Date:||February 2014 (Final data collection date for primary outcome measure)|
The patients will undergo PTA of the extracranial cerebral veins
Procedure: Venous PTA
PTA of the internal jugular and/or azygous vein
Sham Comparator: Controls
The patients will undergo sham procedure
Other: Catheter Venography
The patients will undergo catheter venography but not PTA
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.
|Contact: Graziella Filippini, MD||0039 firstname.lastname@example.org|
|Contact: Paolo Zamboni, MDemail@example.com|
|S. Anna Hospital||Recruiting|
|Ferrara, Fe, Italy, 44100|
|Principal Investigator: Fabrizio Salvi, MD|
|S. Anna Hospital, University of Ferrara, Ferrara, Italy||Recruiting|
|Ferrara, Italy, 44100|
|Contact: Gabriele Rinaldi, MD 00390532236570 firstname.lastname@example.org|
|Contact: Ulriche Wienand, MD 00390532236570 email@example.com|
|Sub-Investigator: Roberto Galeotti, MD|
|Sub-Investigator: Fabrizio Salvi, MD|
|Principal Investigator:||Paolo Zamboni, MD||S. Anna Hospital, University of Ferrara, Ferrara, Italy|
|Study Chair:||Graziella Filippini, MD||Istituto Neurologico Besta, Milano, Italy|