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

Not Applicable

Completed

• Conditions: Venous Insufficiency; Multiple Sclerosis
• Interventions: Procedure: Venous PTA; Other: Catheter Venography

• Registration Number: NCT01371760
• Lead Sponsor: S. Anna Hospital

Brief Summary

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

Safety will be assessed by measuring serious and minor adverse effects related to treatment.

Effectiveness will be assessed by measuring 2 primary endpoints:

1. 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.

2. 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.

Study Timeline

• Study First Submitted: 2011-06-07
• Study First Submitted QC: 2011-06-10
• Study First Posted: 2011-06-13
• Study Start: 2012-08
• Primary Completion: 2014-12
• Status Verified: 2015-12
• Study Completion: 2015-12
• Last Update Submitted: 2015-12-16
• Last Update Posted: 2015-12-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 212

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intervention	Venous PTA	The patients will undergo PTA of the extracranial cerebral veins
Controls	Catheter Venography	The patients will undergo sham procedure

Primary Outcome Measures

Name	Time	Method
Clinical parameters in an integrated functional score	Baseline; 12 months	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.	Baseline; 12 months	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.

Secondary Outcome Measures

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

Trial Locations

Locations (2)

S. Anna Hospital, University of Ferrara, Ferrara, Italy; 🇮🇹 Ferrara, Italy

S. Anna Hospital; 🇮🇹 Ferrara, Fe, Italy