Clinical trial results put liberation therapy controversy to rest

For nearly a decade, some people with multiple sclerosis (MS) have put their hopes in a controversial and invasive surgical intervention to reduce inflammation and avoid disability progression. A new paper, published this month in the journal Neurology, offers conclusive evidence that the procedure does not in fact improve outcomes for those with MS.

The procedure, known as “liberation therapy” but commonly called venoplasty, involved dilating and sometimes stenting veins in the neck where they are naturally narrowed. This was based on a theory known as chronic cerebrospinal venous insufficiency (CCSVI). CCSVI was proposed by Dr. Paolo Zamboni, a physician in Italy who theorized that in some MS patients, narrow veins in the neck contributed to iron accumulation in the brain and spinal cord causing an inflammatory response that was thought to be damaging to the central nervous system.

It was a popular theory, and one that a portion of the MS community rallied around as anecdotal accounts of a major improvement in debilitating symptoms from patients who had received the treatment fueled a degree of hope for those living with the disease.

On social media, despite limited scientific evidence to support the CCSVI theory, there was a clear demand for more information and an eagerness for scientific investigation to affirm or deny the effectiveness of liberation therapy as a potential treatment. For Dr. Anthony Traboulsee (pictured above), Director of the UBC MS & NMO Research Program at the Djavad Mowafaghian Centre for Brain Health and lead investigator on two Canada-wide clinical trials to determine the efficacy of liberation therapy in MS, it was an opportunity to listen to the MS community.

“As scientists receiving public research funding, we do have a responsibility to the public and to our patient communities,” says Dr. Traboulsee. “We need to consider public research questions, and bring our expertise and sound scientific approach to those questions. The relationship between researchers and the public should be mutually engaging.”

A 2018 review of public engagement in CCSVI conducted with Neuroethics Canada researchers Dr. Shelly Benjaminy and Dr. Judy Illes found that the narrative around CCSVI highlighted the importance of drawing a socially minded space for public participation in science.

“Even though the trial was not successful in terms of finding value in venoplasty treatment in MS, many participants in the trial were satisfied that the research answered their questions about the procedure,” says Dr. Traboulsee. “It’s a good thing that there’s an expectation that research be made accessible to patient communities, and that there is an onus on researchers to make their study methods clear and lay-friendly. It’s going to be increasingly important for the scientific community to make every effort to include patient perspectives in our study design and implementation.”

Early results from Dr. Traboulsee’s latest trial were announced at an interventional radiology conference in 2017.

The Canadian Institutes of Health Research said in 2017 that Dr. Traboulsee’s results showed that “there was no statistically significant difference in MS symptoms, either as reported by the patients themselves or as determined by brain imaging and standard clinical assessments by physicians, between patients who received balloon vein dilation, and a control group who received a mock procedure,” and determined at the time that it would not support the use of venoplasty as a therapeutic intervention in patients with MS.

While these most recent results show that venoplasty is ineffective treatment for MS, a 2013 study published in The Lancet and involving researchers from across Canada found that the narrowing in some neck veins associated with CCSVI were just as common in those without MS as those with an MS diagnosis.

Dr. Zamboni acknowledged the ineffectiveness of liberation therapy in a 2018 article in JAMA Neurology, following a randomized multi-centre clinical trial in Italy.

“We hope these findings, coming from a carefully controlled, ‘gold standard’ study, will persuade people with MS not to pursue liberation therapy, an invasive procedure that carries the risk of complications, as well as significant financial cost,” said Dr. Traboulsee last year.

“Fortunately, there are a range of new treatments for MS that have been proven through rigorous studies to be safe and effective at slowing disease progression.”

This study and previous investigations into CCSVI have been substantially funded by the MS Society of Canada. Dr. Traboulsee holds a Research Chair of the MS Society of Canada at the University of British Columbia.