Multiple SclerosisBRAVE-DREAMSNCT01371760
BRAVE-DREAMS (BRAin VEnous DRainage Exploited Against Multiple Sclerosis)
A study testing Venous PTA and Catheter Venography in people with Multiple Sclerosis and Venous Insufficiency, run by S. Anna Hospital at 2 sites in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Multiple Sclerosis, Venous Insufficiency
- What is being tested?
- Venous PTA and Catheter Venography
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 212 participants
- Where
- 2 sitesItaly
- Study dates
- Aug 2012to Dec 2015
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country.
Italy2 sites
S. Anna Hospital
Ferrara, Fe, 44100
S. Anna Hospital, University of Ferrara, Ferrara, Italy
Ferrara, 44100
About this study
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
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.
Read the 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:
- 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.
- 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.
- Conditions
- Multiple Sclerosis, Venous Insufficiency
- Being tested
- Venous PTA, Catheter Venography
- Keywords
- Multiple sclerosis, Chronic cerebrospinal venous insufficiency, Percutaneous Transluminal Angioplasty (PTA), Internal jugular vein, Azygous vein
- Medical subject headings
- Multiple Sclerosis, Venous Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Venous PTAProcedure or surgery
PTA of the internal jugular and/or azygous vein
Catheter VenographyOther
The patients will undergo catheter venography but not PTA
| Study group | Role | What they receive |
|---|---|---|
| Intervention | Experimental | The patients will undergo PTA of the extracranial cerebral veins Receives: Procedure: Venous PTA |
| Controls | Sham comparator | The patients will undergo sham procedure Receives: Other: Catheter Venography |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Baseline; 12 months
Secondary outcomes (8)
EDSS
EDSS will be assessed along 1 year follow-up.
Measured: Baseline; 12 months
Chronic fatigue
This highly disabling symptom completely orphan of effective therapy will be measured by M-FIS (Modified-Fatigue Impact Scale).
Measured: Baseline; 12 months
Cognitive function
Cognitive functions will be measured by the means of MoCA mental state questionnaire.
Measured: Baseline; 12 months
Annualized relapse rate
In the sub population affected by the RR clinical form the number of relapse will be assessed.
Measured: Baseline; 12 months
Patency rate
The rate of successful PTA will be assessed by the means of postoperative Doppler sonography.
Measured: Baseline; 12 months
Emotional status
Anxiety and Depression Scale for use with multiple sclerosis patients will be administered.
Measured: Baseline; 1 year
Memory and cognition
The assessment will be performed by the means of PASAT - Paced Auditory Serial Addition Test
Measured: Baseline; 1 year
Overactive Bladder
Overactive Bladder symptom will be measured by the means of validated Overactive Bladder Questionnaire-b.
Measured: Baseline; 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jun 2011 (estimated)
- Study startAug 2012
- Primary completionDec 2014
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 212 participants (actual)
Sponsor and investigators
- Lead sponsor
- S. Anna Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Regione Emilia-Romagna
- Responsible party
- Principal investigator, Paolo Zamboni, S. Anna Hospital
- Investigators
- Paolo Zamboni, MD, Principal investigator, S. Anna Hospital, University of Ferrara, Ferrara, ItalyGraziella Filippini, MD, Study chair, Istituto Neurologico Besta, Milano, Italy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01371760
- Sponsor's protocol ID
- S. Anna Hospital
- Acronym
- BRAVE-DREAMS
- Status last verified
- Dec 2015
- First submitted
- 7 Jun 2011
- Last updated
- 17 Dec 2015
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Data analysis on behalf of the independent Biostatistic Center will be completed within May 2016
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.
PubMed 19958985Zamboni 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.
PubMed 31735108Zamboni 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.
PubMed 29150995Zamboni 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.
PubMed 23034121
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01371760
- Acronym / sponsor ID
- BRAVE-DREAMS / S. Anna Hospital
- Conditions
- Multiple Sclerosis, Venous Insufficiency
- Keywords
- Multiple sclerosis, Chronic cerebrospinal venous insufficiency, Percutaneous Transluminal Angioplasty (PTA), Internal jugular vein, Azygous vein
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 212 participants (actual)
- Lead sponsor
- S. Anna HospitalUniversity, hospital or other
- Collaborators
- Regione Emilia-Romagna
- Study start
- Aug 2012
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 13 Jun 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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.
- 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intervention | Experimental | Procedure: Venous PTAThe patients will undergo PTA of the extracranial cerebral veins |
| Controls | Sham comparator | Other: Catheter VenographyThe patients will undergo sham procedure |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- patients affected by CCSVI associated with MS
- relapsing-remitting and\or secondary progressive
- 18-65 years old
- EDSS 2-5
- disease duration < 10y
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Venous PTAPTA of the internal jugular and/or azygous vein | Procedure or surgery | Intervention |
| Catheter VenographyThe patients will undergo catheter venography but not PTA | Other | Controls |
Primary outcome
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.
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.
8 secondary outcomes
EDSS
Time frame: Baseline; 12 months
Chronic fatigue
Time frame: Baseline; 12 months
Cognitive function
Time frame: Baseline; 12 months
Annualized relapse rate
Time frame: Baseline; 12 months
Patency rate
Time frame: Baseline; 12 months
Emotional status
Time frame: Baseline; 1 year
Memory and cognition
Time frame: Baseline; 1 year
Overactive Bladder
Time frame: Baseline; 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2015.
- Results publication: PubMed 19958985Zamboni 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.
- Derived from this study: PubMed 31735108Zamboni 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.
- Derived from this study: PubMed 29150995Zamboni 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.
- Derived from this study: PubMed 23034121Zamboni 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.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Data analysis on behalf of the independent Biostatistic Center will be completed within May 2016
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paolo Zamboni, MD principal investigator
S. Anna Hospital, University of Ferrara, Ferrara, Italy
Graziella Filippini, MD study chair
Istituto Neurologico Besta, Milano, Italy
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Venous PTA and Catheter Venography in people with Multiple Sclerosis and Venous Insufficiency, run by S. Anna Hospital at 2 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical parameters in an integrated functional score (time frame: Baseline; 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01371760, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2015.