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

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

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.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis; Venous Insufficiency
• Intervention / Treatment: Procedure: Venous PTA; Other: Catheter Venography

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 Type: Interventional
• Enrollment (Actual): 212
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Ferrara, Italy, 44100
    • S. Anna Hospital, University of Ferrara, Ferrara, Italy
  • Fe
    • Ferrara, Fe, Italy, 44100
      • S. Anna Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: S. Anna Hospital
• Collaborators: 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

Publications and helpful links

General Publications

• 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.
• 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.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (ACTUAL): December 1, 2014
• Study Completion (ACTUAL): December 1, 2015

Study Registration Dates

• First Submitted: June 7, 2011
• First Submitted That Met QC Criteria: June 10, 2011
• First Posted (ESTIMATE): June 13, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): December 17, 2015
• Last Update Submitted That Met QC Criteria: December 16, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: Multiple sclerosis; Internal jugular vein; Chronic cerebrospinal venous insufficiency; Percutaneous Transluminal Angioplasty (PTA); Azygous vein
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Venous Insufficiency
• Other Study ID Numbers: S. Anna Hospital

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data analysis on behalf of the independent Biostatistic Center will be completed within May 2016