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

• ClinicalTrials.gov Identifier: NCT01371760
• Recruitment Status: Completed
• First Posted: June 13, 2011
• Last Update Posted: December 17, 2015
• Sponsor: S. Anna Hospital
• Collaborator: Regione Emilia-Romagna
• Information provided by (Responsible Party): Paolo Zamboni, S. Anna Hospital

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Multiple Sclerosis; Venous Insufficiency	Procedure: Venous PTA; Other: Catheter Venography	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 212 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, 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
• Study Start Date: August 2012
• Actual Primary Completion Date: December 2014
• Actual Study Completion Date: December 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: Intervention; 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

Outcome Measures

Primary Outcome Measures :

1. Clinical parameters in an integrated functional score [ Time Frame: 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.
2. MRI outcome measures: T1Gad active lesion.T2 lesion volume MRI evaluation. [ Time Frame: 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 :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Italy

S. Anna Hospital

Ferrara, Fe, Italy, 44100

S. Anna Hospital, University of Ferrara, Ferrara, Italy

Ferrara, Italy, 44100

Sponsors and Collaborators

S. Anna Hospital

Regione Emilia-Romagna

Investigators

• Principal Investigator: Paolo Zamboni, MD; S. Anna Hospital, University of Ferrara, Ferrara, Italy
• Study Chair: Graziella Filippini, MD; Istituto Neurologico Besta, Milano, Italy

More Information

Additional Information:

Related Info 

Publications of Results:

Zamboni P, Galeotti R, Menegatti E, Malagoni AM, Gianesini S, Bartolomei I, Mascoli F, Salvi F. A prospective open-label study of endovascular treatment of chronic cerebrospinal venous insufficiency. J Vasc Surg. 2009 Dec;50(6):1348-58.e1-3. doi: 10.1016/j.jvs.2009.07.096. Erratum In: J Vasc Surg. 2010 Apr;51(4):1079.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Zamboni P, Galeotti R, Salvi F, Giaquinta A, Setacci C, Alborino S, Guzzardi G, Sclafani SJ, Maietti E, Veroux P; Brave Dreams Research Group. Effects of Venous Angioplasty on Cerebral Lesions in Multiple Sclerosis: Expanded Analysis of the Brave Dreams Double-Blind, Sham-Controlled Randomized Trial. J Endovasc Ther. 2020 Feb;27(1):1526602819890110. doi: 10.1177/1526602819890110. Epub 2019 Nov 17. Erratum In: J Endovasc Ther. 2020 Feb;27(1):NP1.

Zamboni P, Tesio L, Galimberti S, Massacesi L, Salvi F, D'Alessandro R, Cenni P, Galeotti R, Papini D, D'Amico R, Simi S, Valsecchi MG, Filippini G; Brave Dreams Research Group. Efficacy and Safety of Extracranial Vein Angioplasty in Multiple Sclerosis: A Randomized Clinical Trial. JAMA Neurol. 2018 Jan 1;75(1):35-43. doi: 10.1001/jamaneurol.2017.3825.

Zamboni P, Bertolotto A, Boldrini P, Cenni P, D'Alessandro R, D'Amico R, Del Sette M, Galeotti R, Galimberti S, Liberati A, Massacesi L, Papini D, Salvi F, Simi S, Stella A, Tesio L, Valsecchi MG, Filippini G; Chair of the Steering Committee. Efficacy and safety of venous angioplasty of the extracranial veins for multiple sclerosis. Brave dreams study (brain venous drainage exploited against multiple sclerosis): study protocol for a randomized controlled trial. Trials. 2012 Oct 3;13:183. doi: 10.1186/1745-6215-13-183.

• Responsible Party: Paolo Zamboni, PI, S. Anna Hospital
• ClinicalTrials.gov Identifier: NCT01371760
• Other Study ID Numbers: S. Anna Hospital
• First Posted: June 13, 2011
• Last Update Posted: December 17, 2015
• Last Verified: December 2015

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Data analysis on behalf of the independent Biostatistic Center will be completed within May 2016

Keywords provided by Paolo Zamboni, S. Anna Hospital:

Multiple sclerosis; Chronic cerebrospinal venous insufficiency; Percutaneous Transluminal Angioplasty (PTA); Internal jugular vein; Azygous vein

Additional relevant MeSH terms:

Multiple Sclerosis; Venous Insufficiency; Sclerosis; Pathologic Processes; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Vascular Diseases; Cardiovascular Diseases