Prospective Randomized Endovascular Therapy in Multiple Sclerosis - PREMiSE (PREMiSE)
Primary Purpose
Multiple Sclerosis
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Selective Venography followed by therapeutic balloon angioplasty
Control arm
Sponsored by

About this trial
This is an interventional treatment trial for Multiple Sclerosis
Eligibility Criteria
Inclusion Criteria:
- Age 18-65 years
- EDSS 0-6.5 (0-5.5 in the phase II of the study)
- Diagnosis of relapsing MS according to the McDonald criteria (Polman et al., 2005)
- 1 relapse within the past 12 months or GAD positive lesion on an MRI within the past 3 months (only for phase II of the study)
- Be on treatment with currently FDA approved disease-modifying treatments (excluding Tysabri or steroids (within the last 30 days prior to enrollment)
- Evidence of ≥2 sonographic parameters of suspicious abnormal extracranial cerebral venous outflow (see Table 1 background and 1.5 section)
- Normal renal function: creatinine clearance level of >60
Exclusion Criteria:
- Relapse, disease progression and Tysabri and steroid treatment in the 30 days preceding study entry
- Pre-existing medical conditions known to be associated with brain pathology (e.g., neurodegenerative disorder, cerebrovascular disease, positive history of alcohol abuse, etc.)
- Severe peripheral chronic venous insufficiency
- Abnormal renal function
- Contrast allergy (anaphylaxis)
- Not accepting to undergo the endovascular treatment
- Peripheral Vascular Disease
Sites / Locations
- University at Buffalo Neurosurgery
Arms of the Study
Arm 1
Arm 2
Arm Type
Sham Comparator
Active Comparator
Arm Label
Control arm
Active arm
Arm Description
Venography and sham angioplasty
therapeutic balloon angioplasty
Outcomes
Primary Outcome Measures
Safety
- Percent (%) of patients with Severe Adverse Events (SAE) measured at 24 hours (Immediate) and 1 month (Short term) post-surgical safety outcome in MS patients diagnosed with CCSVI that underwent therapeutic angioplasty. . The 95% confidence interval of the SAE rates for immediate and short terms will be obtained by the exact method, respectively. For Phase II study, the immediate and short term SAE rates will be analyzed, respectively, using the Fisher's exact test.
Secondary Outcome Measures
Preliminary efficacy
- Restoration of venous outflow (more than 75% of normal outflow) as measured by the combined ECD/TCD and MRV at 1 month, 3 months, 6 months, and 1 yearfollowing the angioplasty as compared to baseline as well as compared to a parallel control group of MS patients that will undergo only selective venography without balloon angioplasty (sham-angioplasty). These comparisons will be accomplished by the hierarchical linear model which takes into account the correlation within subjects. Based on the residuals, we will check the normality assumptions by the normal quantile plot and skewness.
Full Information
NCT ID
NCT01450072
First Posted
October 6, 2011
Last Updated
May 10, 2016
Sponsor
University at Buffalo Neurosurgery
1. Study Identification
Unique Protocol Identification Number
NCT01450072
Brief Title
Prospective Randomized Endovascular Therapy in Multiple Sclerosis - PREMiSE
Acronym
PREMiSE
Official Title
Prospective Randomized Endovascular Therapy in Multiple Sclerosis - PREMiSE
Study Type
Interventional
2. Study Status
Record Verification Date
May 2016
Overall Recruitment Status
Completed
Study Start Date
June 2010 (undefined)
Primary Completion Date
December 2011 (Actual)
Study Completion Date
December 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University at Buffalo Neurosurgery
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The Departments of Neurology and Neurosurgery are conducting this research study to evaluate the safety and effectiveness of intravascular angioplasty for the treatment of venous narrowing in the treatment of Multiple Sclerosis (MS).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Control arm
Arm Type
Sham Comparator
Arm Description
Venography and sham angioplasty
Arm Title
Active arm
Arm Type
Active Comparator
Arm Description
therapeutic balloon angioplasty
Intervention Type
Device
Intervention Name(s)
Selective Venography followed by therapeutic balloon angioplasty
Intervention Description
Venography followed by therapeutic balloon angioplasty
Intervention Type
Other
Intervention Name(s)
Control arm
Intervention Description
Venography and sham angioplasty
Primary Outcome Measure Information:
Title
Safety
Description
- Percent (%) of patients with Severe Adverse Events (SAE) measured at 24 hours (Immediate) and 1 month (Short term) post-surgical safety outcome in MS patients diagnosed with CCSVI that underwent therapeutic angioplasty. . The 95% confidence interval of the SAE rates for immediate and short terms will be obtained by the exact method, respectively. For Phase II study, the immediate and short term SAE rates will be analyzed, respectively, using the Fisher's exact test.
Time Frame
24 hours-1 month
Secondary Outcome Measure Information:
Title
Preliminary efficacy
Description
- Restoration of venous outflow (more than 75% of normal outflow) as measured by the combined ECD/TCD and MRV at 1 month, 3 months, 6 months, and 1 yearfollowing the angioplasty as compared to baseline as well as compared to a parallel control group of MS patients that will undergo only selective venography without balloon angioplasty (sham-angioplasty). These comparisons will be accomplished by the hierarchical linear model which takes into account the correlation within subjects. Based on the residuals, we will check the normality assumptions by the normal quantile plot and skewness.
Time Frame
1 month, 3 months, 6 months, and 1 yearfollowing
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age 18-65 years
EDSS 0-6.5 (0-5.5 in the phase II of the study)
Diagnosis of relapsing MS according to the McDonald criteria (Polman et al., 2005)
1 relapse within the past 12 months or GAD positive lesion on an MRI within the past 3 months (only for phase II of the study)
Be on treatment with currently FDA approved disease-modifying treatments (excluding Tysabri or steroids (within the last 30 days prior to enrollment)
Evidence of ≥2 sonographic parameters of suspicious abnormal extracranial cerebral venous outflow (see Table 1 background and 1.5 section)
Normal renal function: creatinine clearance level of >60
Exclusion Criteria:
Relapse, disease progression and Tysabri and steroid treatment in the 30 days preceding study entry
Pre-existing medical conditions known to be associated with brain pathology (e.g., neurodegenerative disorder, cerebrovascular disease, positive history of alcohol abuse, etc.)
Severe peripheral chronic venous insufficiency
Abnormal renal function
Contrast allergy (anaphylaxis)
Not accepting to undergo the endovascular treatment
Peripheral Vascular Disease
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Adnan Siddiqui, MD, PhD
Organizational Affiliation
University at Buffalo Neurosurgery
Official's Role
Principal Investigator
Facility Information:
Facility Name
University at Buffalo Neurosurgery
City
Buffalo
State/Province
New York
ZIP/Postal Code
14209
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
24975855
Citation
Siddiqui AH, Zivadinov R, Benedict RH, Karmon Y, Yu J, Hartney ML, Marr KL, Valnarov V, Kennedy CL, Ramanathan M, Ramasamy DP, Dolic K, Hojnacki DW, Carl E, Levy EI, Hopkins LN, Weinstock-Guttman B. Prospective randomized trial of venous angioplasty in MS (PREMiSe). Neurology. 2014 Jul 29;83(5):441-9. doi: 10.1212/WNL.0000000000000638. Epub 2014 Jun 27. Erratum In: Neurology. 2014 Aug 19;83(8):773.
Results Reference
derived
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Prospective Randomized Endovascular Therapy in Multiple Sclerosis - PREMiSE
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