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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2012 by S. Anna Hospital.
Recruitment status was  Recruiting
Sponsor:
Collaborators:
Regione Emilia-Romagna
Fondazione Hilarescere, Bologna, Italy
Information provided by (Responsible Party):
Paolo Zamboni, S. Anna Hospital
ClinicalTrials.gov Identifier:
NCT01371760
First received: June 7, 2011
Last updated: August 21, 2012
Last verified: August 2012
  Purpose

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.


Condition Intervention Phase
Multiple Sclerosis
Venous Insufficiency
Procedure: Venous PTA
Other: Catheter Venography
Phase 3

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by S. Anna Hospital:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 679
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)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01371760

Contacts
Contact: Graziella Filippini, MD 0039 0223941 gfilippini@istituto-besta.it
Contact: Paolo Zamboni, MD 00390532237694 zmp@unife.it

Locations
Italy
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    g.rinaldi@ospfe.it   
Contact: Ulriche Wienand, MD    00390532236570    u.wienand@ospfe.it   
Sub-Investigator: Roberto Galeotti, MD         
Sub-Investigator: Fabrizio Salvi, MD         
Sponsors and Collaborators
S. Anna Hospital
Regione Emilia-Romagna
Fondazione Hilarescere, Bologna, Italy
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:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Paolo Zamboni, PI, S. Anna Hospital
ClinicalTrials.gov Identifier: NCT01371760     History of Changes
Other Study ID Numbers: S. Anna Hospital
Study First Received: June 7, 2011
Last Updated: August 21, 2012
Health Authority: Regione Emilia Romagna: Italy

Keywords provided by S. Anna Hospital:
Multiple sclerosis
Chronic cerebrospinal venous insufficiency
Percutaneous Transluminal Angioplasty (PTA)
Internal jugular vein
Azygous vein

Additional relevant MeSH terms:
Sclerosis
Multiple Sclerosis
Venous Insufficiency
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

ClinicalTrials.gov processed this record on September 18, 2014