OBJECTIVE: We report the results of the investigation of safety and efficacy of 
venous angioplasty in patients with multiple sclerosis (MS) with findings of 
extracranial venous anomalies, considered hallmarks of chronic cerebrospinal 
venous insufficiency (CCSVI), in a 2-phase study (ClinicalTrials.gov 
NCT01450072).
METHODS: Phase 1 was an open-label safety study (10 patients); phase 2 was 
sham-controlled, randomized, and double-blind (10 sham procedure, 9 treated). 
All study patients fulfilled venous hemodynamic screening criteria indicative of 
CCSVI. Assessment was at 1, 3, and 6 months postprocedure with MRI, clinical, 
and hemodynamic outcomes. Primary endpoints were safety at 24 hours and 1 month, 
venous outflow restoration >75% at 1 month, and effect of angioplasty on new 
lesion activity and relapse rate over 6 months. Secondary endpoints included 
changes in disability, brain volume, cognitive tests, and quality of life.
RESULTS: No perioperative complications were noted; however, one patient with 
history of syncope was diagnosed with episodic bradycardia requiring placement 
of a pacemaker before discharge. Doppler evidence-based venous hemodynamic 
insufficiency severity score (VHISS) was reduced >75% compared to baseline in 
phase 1 (at 1 month) but not phase 2. In phase 2, higher MRI activity 
(cumulative number of new contrast-enhancing lesions [19 vs 3, p = 0.062] and 
new T2 lesions [17 vs 3, p = 0.066]) and relapse activity (4 vs 1, p = 0.389) 
were identified as nonsignificant trends in the treated vs sham arm over 6 
months. Using analysis of covariance, significant cumulative new T2 lesions were 
related to larger VHISS decrease (p = 0.028) and angioplasty (p = 0.01) over the 
follow-up. No differences in other endpoints were detected.
CONCLUSION: Venous angioplasty is not an effective treatment for MS over the 
short term and may exacerbate underlying disease activity.
CLASSIFICATION OF EVIDENCE: This is a Class I study demonstrating that clinical 
and imaging outcomes are no better or worse in patients with MS identified with 
venous outflow restriction who receive venous angioplasty compared to sham 
controls who do not receive angioplasty. This study also includes a Class IV 
phase 1 study of safety in 10 patients receiving the angioplasty procedure.