North American researchers investigating the controversial Zamboni theory of multiple sclerosis are running into a host of problems with their trials that threaten to delay meaningful results.
The problems, documented in a new progress report, call into question the timing of Ottawa’s decision last month to announce support for formal clinical trials of the vein-widening treatment in Canada.
Problems with the trials include difficulty recruiting study participants, challenges figuring out how to properly identify and diagnose venous problems and trouble obtaining ethics approval to conduct research.
The report comes in contrast to optimistic comments from the federal government and Canadian Institutes of Health Research last month, which said there is now enough evidence of a link between blocked veins and MS to warrant funding for the first clinical treatment trial here.
An expert panel led by CIHR said the decision was based in part on preliminary results from the seven trials funded by the MS societies, as well as other published research looking into blocked neck veins.
But the new report makes it clear the clinical trials, which focus mainly on determining whether venous abnormalities are present in MS patients and healthy controls, remain a long way from producing results that can either support or poke holes into the blocked-veins theory.
“None of [the studies] are going to go according to a set schedule,” said Stewart Wong, spokesman for the MS Society of Canada. “There’s going to be variability.”
One researcher leading one of the seven clinical trials suggested it may have been premature for the CIHR to suggest a definitive association between blocked or malformed neck veins and MS.
“I’m not sure that all of us would be universal in our embracing that position at the present time,” said Jerry Wolinsky, a neurology professor at the University of Texas Medical School at Houston.
The blocked-veins theory, made popular by Italian doctor Paolo Zamboni, flies in the face of what experts have long believed: that MS is an autoimmune disorder. It has become a flashpoint in Canada, where thousands of patients have flown around the world to have vein-widening surgery, usually at high costs. Several people, including two Canadians, have died after receiving the treatment.
After months of pressure from patients and advocates, the federal government announced last month it would fund clinical trials of the procedure here.
The seven clinical studies funded by the MS societies, which began a year ago, were designed to take two years in total. But emerging problems raise questions about whether those timelines will be met.
For instance, one study out of the University of Wisconsin only just received approval from the institution to go ahead.
“It’s just a very long process,” said Aaron Field, associate professor of neuroradiology at the University of Wisconsin School of Medicine and Public Health. “We’re really in the very early stages.”
Another study is facing challenges recruiting participants. Some of the MS patients recruited to take part in the study subsequently travelled to clinics to get the vein-widening procedure, making them ineligible to continue in the study. Dr. Wolinsky, who is leading that study, also said they are having trouble recruiting patients with other neurological disorders who can be compared with MS patients in the study.
Other researchers have spent months developing the proper “protocols” for identifying blocked veins.
Drs. Wolinsky and Field said one of the main issues is that designing a proper clinical trial, particularly in a relatively new and controversial area, is a painstaking, time-consuming process.
“It really takes time to make sure all the i’s are dotted and t’s are crossed,” Dr. Field said. “Given the high-profile nature of this particular focus, people are being extra careful I think to really make sure the studies are done carefully and with attention to scientific standards.”
Ian MacLeod of Richmond, B.C., is one of the MS patients who will be watching the outcome of these studies. Mr. MacLeod, who has difficulty walking and a range of other symptoms, travelled to the U.S. a few weeks ago to get the vein-widening procedure. He debated the decision for months, but ultimately decided to see if it would do any good.
He says it is now easier to climb stairs and that he doesn’t get up as often to go to the bathroom in the middle of the night, a common MS symptom. While he hopes he will continue to improve, he admits he remains somewhat skeptical about the blocked-veins theory.
“Anybody I think that’s expecting this as a panacea is maybe overly wishful in their thinking,” he said. “But again, everybody needs hope, and what price do you put on hope?”