TORONTO - A long-awaited national trial of a controversial experimental treatment for multiple sclerosis has been given the go-ahead and will soon begin recruiting patients, federal Health Minister Leona Aglukkaq announced Friday.
Aglukkaq, in Halifax for a meeting with provincial and territorial health ministers, said about 100 MS patients will be enrolled in the Phase I and II trial to assess the safety of the procedure to unblock narrowed neck veins and its efficacy in improving MS symptoms.
The condition — dubbed chronic cerebrospinal venous insufficiency, or CCSVI — has been proposed as a possible cause of MS by Italian vascular surgeon Paolo Zamboni.
More than three years ago, Zamboni hypothesized 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 brain lesions typical of MS.
The disease causes the destruction of myelin, the protective sheath around nerves throughout the body, leading to progressive physical and cognitive disability. 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.
"We've always said that we needed the science behind the actual procedure," Aglukkaq told reporters. "This area of MS clinical trials is very important to many of our constituents and today is huge progress."
Dr. Anthony Traboulsee, medical director of UBC Hospital's MS Clinic, will lead the $6-million study, which will be conducted initially in Vancouver and Montreal. Medical and ethical approval is also being sought for parts of the trial to be conducted in Quebec City and Winnipeg.
"It's going to be a randomized-control study where patients who have the presence of CCSVI will be randomly selected to either have the venoplasty, which is dilation of the vein, or a sham treatment, which is not an actual dilation, just a pretend dilation," Traboulsee said from Vancouver.
"And after a year, the groups will switch so that everybody eventually gets the dilation of the vein."
A venoplasty to widen veins is the same technique as an angioplasty used to expand coronary arteries; a tiny balloon is fed into the blood vessel, then expanded.
None of the participants will know which treatment they received or during which half of the study, Traboulsee said.
"The patients won't know when they're getting the dilation, the first time or the second time, so it doesn't bias their interpretation of benefit," he said.
Despite criticisms of Zamboni's theory — some neurologists question or even outright dismiss the notion of blocked veins contributing to MS — many patients desperate for relief have embraced the treatment.
Thousands of Canadians with MS have reportedly travelled to clinics outside the country, paying thousands of dollars for the vein-widening procedure since Zamboni's theory first made headlines in late 2009.
Many patients — but by no means all — reported their symptoms had improved following CCSVI treatment, fuelling insistent calls by many MS patients and their advocates to allow doctors to perform the procedure in Canada.
But with several deaths and complications attributed to the surgery, and studies on CCSVI around the world showing mixed results at best, an expert medical panel advised Ottawa to first mount a clinical trial to test Zamboni's theory.
Traboulsee's group, whose study design was chosen from among three proposals, said "safety is really important."
"We've been surveying patients who have gone out of the country for the treatment and we found a complication rate of 11 to 12 per cent. That's what patients are reporting," he said.
"My impression is it's mostly related to stents, and we're not going to be using stents in our study. We don't think the stents are the best idea at this point."
Stents are small mesh cylinders inserted into blood vessels to keep them propped open. Their use in veins is controversial, as the stents can cause blood clots or migrate from their original site. Even Zamboni does not advocate their use in his CCSVI treatment.
"There has been a lot of controversy around it," Traboulsee said of the procedure. "That's why I think it's important to move this forward and get some final answers to it.
"Because so many Canadians are going out of the country to have this procedure done, if we don't bring some resolution to it soon, we won't be able to give people the information they need to make safe, informed decisions."
A spokesman for the CCSVI Coalition, a patient advocacy group that's been pushing to have the treatment performed in Canada, welcomed the announcement of the study.
"It's long overdue," said Dr. Michael Shannon, chair of the group's scientific advisory board. "If the results from this trial come out unequivocally in favour of CCSVI or the other way, either way it's good news — if and only if the trial has been designed properly.
"If it is flawed in any way, you'll be right back to the drawing board and you'll never be able to convince everyone. So this thing has to be so rigorous."
Dr. Alain Beaudet, president of the Canadian Institutes of Health Research (CIHR), said trial subjects will be drawn from the three provinces where the research is being conducted.
Beaudet said the study is among only a handful worldwide that are blinded, randomized-control trials, the gold standard of medical research.
"Which is critical here, because we're wondering if it's a true effect. Is it a placebo effect? Is there really an effect?" he said from Halifax.
Saskatchewan has set aside $5 million for clinical trials of the so-called liberation therapy; $2.2 million of that is funding a trial of the procedure involving 86 patients from the province, being conducted at a clinic in Albany, N.Y.
Provincial Health Minister Dustin Duncan said the rest of the money could go toward a pan-Canadian trial.
"What has been announced today is just the beginnings, I think, of what the federal government is doing," Duncan told The Canadian Press. "We certainly want to be a part of whether it's in trials or whether it's in monitoring ... we want to be a part of trying to answer that question of whether CCSVI is an effective treatment for people with MS."
The national study is funded by the federal government through CIHR, the three provinces where it is taking place, and the MS Society of Canada.
Traboulsee said researchers will use not only standard yardsticks to evaluate patients during the study period, but also some patient-focused measures.
"We've had a lot of patient input into the study, so it's a nice balance of what we consider a classic standard MS clinical trial, with a lot of patient input into the outcome," he said.
"So it's in a sense validated by the patient support groups in that it's addressing questions that they think are important to them as well as to the clinicians."
Trial information: www.vchri.ca/s/MS-CCSVI-PII.asp
—With files from CP reporters Jennifer Graham in Regina and Michael Tutton in Halifax.