Prospective Randomized Endovascular Therapy in Multiple Sclerosis - PREMiSE (PREMiSE)

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).

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Other: Control arm; Device: Selective Venography followed by therapeutic balloon angioplasty

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14209
      • University at Buffalo Neurosurgery

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: Control arm; Venography and sham angioplasty	Other: Control arm; Venography and sham angioplasty
Active Comparator: Active arm; therapeutic balloon angioplasty	Device: Selective Venography followed by therapeutic balloon angioplasty; Venography followed by therapeutic balloon angioplasty

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	24 hours-1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	1 month, 3 months, 6 months, and 1 year post-angioplasty

Collaborators and Investigators

• Sponsor: State University of New York at Buffalo
• Investigators: Principal Investigator: Adnan Siddiqui, MD, PhD, University at Buffalo Neurosurgery

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: October 6, 2011
• First Submitted That Met QC Criteria: October 7, 2011
• First Posted (Estimated): October 12, 2011

Study Record Updates

• Last Update Posted (Actual): June 18, 2025
• Last Update Submitted That Met QC Criteria: June 16, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Pathologic Processes; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Multiple Sclerosis; Sclerosis
• Other Study ID Numbers: NSG1730210B (Other Identifier: HSIRB - SUNY Buffalo)