Randomised trial finds no difference in changes between MS patients who had sham angioplasty or balloon venoplasty

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Lindsay Machan

Venoplasty is not effective in treating multiple sclerosis, according to the first presentation of interim data from a randomised, double blind clinical trial of jugular and azygous venoplasty in multiple sclerosis. Lindsay Machan, University of British Columbia (UBC) and Vancouver Coastal Health, presented the data at the Society of Interventional Radiology’s annual scientific meeting in Washington, DC, USA.

“In our study, we found no difference in subjective or objective changes between patients who had sham angioplasty or balloon venoplasty,” Machan told Interventional News.

These data concerning the “liberation therapy,” which thousands of people with multiple sclerosis have undergone since 2009, do not support the claim that multiple sclerosis patients can achieve dramatic improvements from a one-time medical procedure.

The multicentre prospective randomised blinded sham-controlled trial of jugular venoplasty in multiple sclerosis study set out to compare the clinical efficacy of balloon venoplasty vs. sham angioplasty of jugular and azygous vein stenoses in patients with multiple sclerosis 48 weeks post procedure.

“I do believe this to be the most rigidly scientifically conducted assessment of chronic cerebrospinal venous insufficiency (CCSVI) to date. These results constitute a mid-term report of our study. We have seen highly respected practitioners of our specialty observe marked improvement in some patients and although in this mid-term report we did not observe differences in outcome between sham and balloon venoplasty, I await with interest the final dataset when we will compare the results in individual patients,” Machan explained.

“After week 48, all patients underwent a crossover procedure (those who had the sham procedure at week 0 had balloon angioplasty and vice versa). All patients have now had their crossover procedures and are being followed for another 48 weeks after that. We expect the final report sometime in Autumn,” he added.

“We hope these findings, coming from a carefully controlled, ‘gold standard’ study, will persuade people with multiple sclerosis not to pursue liberation therapy, an invasive procedure that carries the risk of complications, as well as significant financial cost,” said Anthony Traboulsee, a UBC associate professor of Neurology and director of the MS Clinic at the Djavad Mowafaghian Centre for Brain Health. “Fortunately, there are a range of drug treatments for multiple sclerosis that have been proven through rigorous studies to be safe and effective at slowing disease progression.”

Multiple sclerosis patients, including relapsing and progressive, from four academic clinics, recruited after clinical and ultrasound screening were blinded by deep conscious sedation. If catheter venography confirmed jugular or azygous vein stenosis, they were prospectively randomised 1:1 intra-procedure by sealed envelope to receive balloon or sham venoplasty of all stenoses.

The study was “double-blinded”: Neither the patients nor the physicians who evaluated them knew who was receiving the actual treatment or the sham procedure. The study had some people undergo a “sham” procedure. All 104 participants had a catheter inserted into their blocked veins, but only 49 had venoplasty.

Patient questionnaires were given at baseline, 24 hours and 12 weeks, physical exam at the baseline and at weeks 12, 24, 36, and 48, and MR at baseline and weeks 24 and 48. Safety outcomes including serious adverse events, venous thrombosis, and restenosis were monitored by an independent data safety monitoring board, and clinical trial monitors provided trial oversight. Patients initially randomised to venoplasty received a sham procedure one year later, and vice versa. Extensive efforts were made so the patient experience was the same for both procedures.

A year later, the venoplasty group’s results were statistically the same as those in the sham group, as measured by brain imaging, standard assessments of multiple sclerosis symptoms and the patients’ own self-assessments.

The researchers found no statistically significant difference between the treatment group and the sham group in patient symptoms, either as reported by the patients or as determined by physicians, three days after the procedure and a year later. Both groups showed slight but equal improvements a year later in the patients’ own assessments; physician assessments showed no improvement in either group.

MRI of their brains was used to count the number of new lesions in their myelin, and researchers found no difference between the treatment group and the placebo group at six months and one year later.

The researchers are now preparing an article, based on the US$5.4-million study, jointly funded by the Canadian Institutes of Health Research, the MS Society of Canada, and the provinces of British Columbia, Manitoba and Quebec, for publication in a peer-reviewed journal.

Using venoplasty as a multiple sclerosis treatment was first put forward by vascular surgeon Paolo Zamboni of Italy, who asserted that narrowing of the veins in the neck could be causing iron to accumulate in the brain and spinal cord, triggering an autoimmune response. He called his theory chronic cerebrospinal venous insufficiency (CCSVI), and cited several dozen cases of patients who improved after undergoing venoplasty performed by him.

Many patients in Canada and Europe, upon learning of those anecdotal results through the news media, asked for imaging of their veins and subsequent venoplasty. But almost all Canadian physicians, citing the lack of supporting evidence, would not perform it, prompting some patients to seek the treatment in the USA, Latin America and Eastern Europe.

This is the second study to be led by the UBC and Vancouver Coastal Health team and involving researchers from across Canada that aimed to seek more evidence on the CCSVI theory. The first study, published in The Lancet in 2013 and supported by the MS Society of Canada, sought to determine if narrowed veins was a distinct feature of multiple sclerosis and found that narrowing was just as common in people without the disease.

“Despite the negative findings of that diagnostic study, many patients wanted to know if the venous dilation procedure could help,” said Machan. “We were committed to meticulously evaluating this treatment with robust methods and patient-focused outcomes.”