Clinical trial NCT01371760: BRAVE-DREAMS (BRAin VEnous DRainage Exploited Against Multiple Sclerosis)
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Multiple Sclerosis
Venous Insufficiency
Keywords: Multiple sclerosis
Chronic cerebrospinal venous insufficiency
Percutaneous Transluminal Angioplasty (PTA)
Internal jugular vein
Azygous vein
Lead sponsor: S. Anna Hospital
Sponsor class: OTHER
Collaborators: name: Regione Emilia-Romagna
First posted: 2011-06-13
Enrollment: 212
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Clinical parameters in an integrated functional score
timeFrame: Baseline; 12 months
measure: MRI outcome measures: T1Gad active lesion.T2 lesion volume MRI evaluation.
timeFrame: Baseline; 12 months
Secondary outcomes:
measure: EDSS
timeFrame: Baseline; 12 months
measure: Chronic fatigue
timeFrame: Baseline; 12 months
measure: Cognitive function
timeFrame: Baseline; 12 months
measure: Annualized relapse rate
timeFrame: Baseline; 12 months
measure: Patency rate
timeFrame: Baseline; 12 months
measure: Emotional status
timeFrame: Baseline; 1 year
measure: Memory and cognition
timeFrame: Baseline; 1 year
measure: Overactive Bladder
timeFrame: Baseline; 1 year
Other outcomes:
Locations:
city: Ferrara
country: Italy
facility: S. Anna Hospital
state: Fe
city: Ferrara
country: Italy
facility: S. Anna Hospital, University of Ferrara, Ferrara, Italy
Study officials:
affiliation: S. Anna Hospital, University of Ferrara, Ferrara, Italy
name: Paolo Zamboni, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Istituto Neurologico Besta, Milano, Italy
name: Graziella Filippini, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.