Multiple Sclerosis
Conditions
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).
Interventions
DEVICESelective Venography followed by therapeutic balloon angioplasty
Venography followed by therapeutic balloon angioplasty
OTHERControl arm
Venography and sham angioplasty
Sponsors
State University of New York at Buffalo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With Immediate and Short-term SAE | 24 hours-1 month | Percent (%) of patients with Severe Adverse Events (SAE) measured at 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. The immediate and short term SAE rates will be analyzed, respectively, using the Fisher's exact test. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With More Than 75% of Normal Outflow at 1 Year Post-angioplasty | 1 month, 3 months, 6 months, and 1 year post-angioplasty | Restoration of venous outflow (more than 75% of normal outflow) as measured by the combined ECD/TCD and MRV at 1 year following 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Control Arm Venography and sham angioplasty
Control arm: Venography and sham angioplasty | 10 |
| Active Arm therapeutic balloon angioplasty
Selective Venography followed by therapeutic balloon angioplasty: Venography followed by therapeutic balloon angioplasty | 9 |
| Total | 19 |
Baseline characteristics
| Characteristic | Active Arm | Total | Control Arm |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 19 Participants | 10 Participants |
| Age, Continuous | 43.3 years STANDARD_DEVIATION 8.2 | 44.1 years STANDARD_DEVIATION 9.4 | 44.8 years STANDARD_DEVIATION 10.5 |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment United States | 9 participants | 19 participants | 10 participants |
| Sex: Female, Male Female | 5 Participants | 13 Participants | 8 Participants |
| Sex: Female, Male Male | 4 Participants | 6 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 10 | 3 / 9 |
| serious Total, serious adverse events | 0 / 10 | 0 / 9 |
Outcome results
Primary
Percentage of Patients With Immediate and Short-term SAE
Percent (%) of patients with Severe Adverse Events (SAE) measured at 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. The immediate and short term SAE rates will be analyzed, respectively, using the Fisher's exact test.
Time frame: 24 hours-1 month
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Control Arm | Percentage of Patients With Immediate and Short-term SAE | 0 Participants |
| Active Arm | Percentage of Patients With Immediate and Short-term SAE | 0 Participants |
Secondary
Number of Participants With More Than 75% of Normal Outflow at 1 Year Post-angioplasty
Restoration of venous outflow (more than 75% of normal outflow) as measured by the combined ECD/TCD and MRV at 1 year following 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 year post-angioplasty
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Control Arm | Number of Participants With More Than 75% of Normal Outflow at 1 Year Post-angioplasty | 0 Participants |
| Active Arm | Number of Participants With More Than 75% of Normal Outflow at 1 Year Post-angioplasty | 0 Participants |