TORONTO - A small clinical trial of the so-called "liberation treatment" for multiple sclerosis has found that the intervention did not improve patients' symptoms and in some cases even made their disease worse.
The University of Buffalo study of 30 MS patients concluded that the treatment — which unblocks neck veins to improve blood drainage from the brain — is safe. But researchers say the procedure showed no benefit on numerous measures of symptoms, disease progression and quality of life.
As well, MRI scans showed some patients had increased brain lesions, one of the hallmarks of the progressive neurological disease, after undergoing the vein-opening procedure.
"What we found was rather surprising and unexpected," said neurosurgeon Dr. Adnan Siddiqui, co-principal investigator of the pilot study. "It was quite the opposite of what we originally expected to find. The study showed that endovascular treatment of stenosed (blocked) veins had no effect in MS patients."
Despite the findings, both Saskatchewan and Health Canada said Friday they are going ahead with separate trials to determine whether the experimental treatment for MS has any validity.
The idea was first put forward by Italian vascular surgeon Paulo Zamboni, who hypothesized in 2009 that narrowed and twisted veins in the neck and chest create a backup of blood in the brain, resulting in iron deposits that could cause the lesions typical of MS.
Zamboni dubbed the abnormality "chronic cerebrospinal venous insufficiency," or CCSVI. He suggested it might be a cause of MS and that opening up the veins with balloon angioplasty, the same procedure used to unblock coronary arteries, could help relieve symptoms and might even stop progression of the disease.
Since then, an estimated 30,000 MS patients worldwide have sought the therapy in clinics that have popped up in such countries as Poland, Bulgaria, India and Mexico, and to a lesser extent in the United States.
Included among those medical tourists are thousands of Canadians with MS: the unproven treatment is not offered in Canada.
An estimated 55,000 to 75,000 Canadians have MS, and the country has one of the highest rates of the incurable disease in the world. MS causes the destruction of myelin, the protective sheath around nerves throughout the body, leading to progressive physical and cognitive disability.
The Buffalo trial set out to assess the safety of venous angioplasty for MS patients and its effectiveness by comparing subjects given the vein-clearing procedure and those who received a sham treatment.
The first 10 patients all got the procedure, then in a second phase of 20 more patients, half received venous angioplasty while the other 10 got the bogus therapy. None of the participants knew which treatment they were getting.
The findings suggest "that there's likely no benefit and possibly harm to venous angioplasty," Siddiqui said Friday from Buffalo.
"However, is this the last word on venous angioplasty? Absolutely not. I think a much larger cohort (group of patients) would be required to really demonstrate that definitively."
Federal Health Minister Leona Aglukkaq acknowledged that there are questions about the procedure that need to be answered.
"Clinical trials for CCSVI have been approved and recruitment for participants will begin soon," Aglukkaq said by email, referring to the $6-million study of about 100 patients with CCSVI, who will be randomly assigned to have a venoplasty or a sham treatment.
The Saskatchewan government is also proceeding with its $2.2-million trial, which will see 86 MS patients from the province treated at a clinic in Albany, N.Y.
"At this point, with the limited information that has been put out ... it's not causing us to hesitate in moving forward with the work that we have underway," said Deb Jordan, executive director of acute and emergency services with Saskatchewan's Ministry of Health.
"However, we would expect that the detailed findings that the University of Buffalo has, we would hope that that information would be shared with the other research teams in Canada and the U.S., who have trials underway."
More detailed findings will be presented Wednesday at the annual American Academy of Neurology meeting in San Diego.
Meanwhile, the researchers cautioned that MS patients should only consider seeking the procedure as part of a clinical trial, instead of going to clinics that charge thousands of dollars for their services.
"Our strong recommendation to patients and to practitioners, who have been seeking betterment for their disease and a cure for MS, is that they should instead consider enrolling in trials, rather than undergoing these procedures."
Even so, Siddiqui said the study does not entirely negate the hypothesis that CCSVI may have a role to play in MS or other neurological diseases.
"That relationship remains extremely interesting and certainly we remain committed to evaluating that further and understanding that relationship further," he said.
"Our finding only suggests that using a balloon to open up observed venous narrowings in our cohort of patients, which was very carefully selected, did not show any benefit and demonstrated possible harm when looking at MRI activity."
So perhaps using balloon angioplasty isn't the right treatment option, Siddiqui suggested.
"I'm convinced that this particular intervention does not work for this particular disease finding," he said.
"So what we'd like to do is take a step back and really understand the disease further, so we could come up with a much more directed hypothesis as to what kind of intervention will actually work for these patients."
The Buffalo research group has conducted more than 25 studies on CCSVI and its relationship to neurological diseases, including MS.
"Our findings over the last three years have indicated that CCSVI is more prevalent in MS patients than in healthy controls, but the cause or consequence of these venous abnormalities has not been established," said Dr. Robert Zivadinov, director of the Buffalo Neuroimaging Analysis Center and co-principal investigator of the clinical trial.
However, some groups have not found a higher prevalence of CCSVI in people with MS.
One of those teams is at the University of Texas, which just published its findings on the presence of CCSVI in 276 subjects, some with MS and others without the disease.
The study is the first of seven research projects funded with a joint $2.3-million grant from the U.S. National MS Society and the MS Society of Canada — and it, too, casts doubt on Zamboni's theory.
After putting participants through several vein-imaging methods, the researchers found that CCSVI occurs at a low rate both in those with MS (four per cent) and without MS (seven per cent).
"Our results in this phase of the study suggest that findings in the major veins that drain the brain consistent with CCSVI are uncommon in individuals with MS and quite similar to those found in our non-MS volunteers," said principal investigator Dr. Jerry Wolinsky, director of the university's Health MS Research Group.
"This makes it very unlikely that CCSVI could be the cause of MS, or contribute in an important manner to how the disease can worsen over time."
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