Frequently Asked Questions

FAQs about the federal government funding of CCSVI clinical trials through CIHR.

Q: At what stage if the federal funding announcement - as of June 30, 2011?

A: On June 29, the Canadian government announced that it will be funding a CCSVI clinical trial through CIHR. CIHR has yet to develop the criteria or timelines for the application process, including the amount of funding that will be granted and the number and size of studies that will be funded. As soon as this has been established, CIHR will be putting out a call to research groups across Canada to apply for funding.

MS Society Response:

Q: What does this announcement mean for patients of UBC Hospital MS Clinic?

A: Once the grant application protocol is announced, UBC Hospital MS Clinic researchers and clinicians will review the grant application procedure, at which point they will be able to determine whether or not they will apply to undertake or participate in the trial.

Interventional venous treatment for CCSVI is not available in Canada and is still considered very experimental. Staff and clinicians at UBC Hospital MS Clinic still do not recommended Canadians travel outside the country to seek treatment at this point as we currently do not fully understand the safety implications and effectiveness and sustainability of the procedure.

Q: The UBC Hospital MS Clinic is currently doing one CCSVI related study with Saskatchewan; what is the current status of BC/SASK collaborative CCSVI research study?

A: Researchers are using three diagnostic tests to investigate CCSVI as a medical condition and determine how best to image it. Specifically, researchers are studying both MS patients and healthy controls to better understand the prevalence of abnormal vein activity in both populations. The team is also investigating the use of catheter venography as the "gold standard" to detect CCSVI. Catheter venography is being compared with ultrasound and Magnetic Resonance Imaging to determine which of these tests are adequate and reliable for detecting CCSVI.

The study has been underway at the UBC Hospital MS Clinic and the MS Clinic at Saskatchewan General Hospital for several months. 200 patients have been enrolled. It is the largest comprehensive imaging study of CCSVI that has ever been undertaken. The study concludes December 2011.

Q: What other CCSVI activities is the UBC Hospital MS Clinic involved in?

A: UBC Hospital MS Clinic has launched a new program to better understand the impact of interventional venous treatment. The Clinic has received over $700,000 in provincial funding to establish a CCSVI patient registry, care-related protocols, and a rapid access pathway to expert care for both patients and health care providers. This program has been established to follow British Columbians who have undergone interventional venous treatment oversees in the past 12-18 months.

The provincial funding is spread over three years and allows the UBC Hospital MS Clinic to establish post-care treatment guidelines; a voluntary registry to determine the number of BC residents who have had testing and/or liberation treatment overseas, and the perception of benefits and complications; and a rapid-access to expert care pathway. This key component of the program will enable health care providers across the province to reach one of the experts at the UBC Hospital MS Clinic in situations of need.

FAQs about the BC/SASK CCSVI Study

Q: When will the BC/SASK CCSVI study start?

A: The funding period begins July 1st, 2010. Applications have already been submitted to research ethics boards at each institution. The research ethics board is a group of individuals (scientists, physicians, ethicists, lawyers, and members of the community) that provide an independent review of human research studies. Ethics approval can take weeks or months depending on the nature of the study. We are targeting to start the study in July or August 2010.

Q: How can I participate?

A: This initial study will recruit 100 MS and 100 non-MS subjects from existing patient rosters at the MS Clinic at UBC Hospital and the Saskatoon MS Clinic. Letters of invitation will be sent to all potentially eligible subjects identified from these rosters by the research team. This will include subjects with twins or family members with confirmed MS. This group of subjects will allow us to verify the condition of CCSVI and to determine if there is a genetic (inherited) link to this condition.

Q: I am not a patient at the MS Clinic at UBC Hospital. Am I eligible to enrol in the study?

A: This initial study will be limited to subjects from existing patient rosters at the centers. Some subjects in BC who are followed at another MS clinic in BC (e.g. Victoria,Prince George, Kelowna, Burnaby) could be eligible if they have participated in the Canadian Collaborative Genetics Study in MS at some point over the last 10 years and otherwise meet enrolment criteria. Letters of invitation will go out to eligible participants.

Q: What can I do if I am not selected?

A: Your continued support of our research efforts in CCSVI, even if you are not a subject for this specific study, will help us to understand CCSVI and this will benefit all those affected by MS. We believe that this will be only the beginning. Future studies will depend on the results of this research that must be done with the utmost care and integrity.

Q: How long will the diagnostic study take to complete and until we see results?

A: We expect to have all subjects recruited, and all diagnostic studies analyzed before the end of the two year funding period.

Q: CCSVI is being screened/diagnosed at many global centres already. How can this be happening without the proper studies and do we really need a study to look at diagnostic validation?

A: A goal of our study is to verify Dr. Zamboni's findings on the hypothesis of CCSVI and to determine if ultrasound or MRI venography are accurate enough to detect this proposed condition.

Q: Will participants have the Liberation treatment?

A: This particular study is only focused on imaging and the best method to detect this proposed condition. However, we are actively fundraising for and will be applying for further funding to undertake a treatment study if our initial findings support this approach.

Q: Who will be eligible for future studies?

A: We do not know at this time. We will not know until we have a better understanding about CCSVI and MS.

Q: Would having testing done at a private facility increase my chances of participating?

A: No.

Q: Why are more centers not involved besides BC and Saskatchewan?

A: In 2009, the MS programs in BC and Saskatchewan joined together as the Western Pacific Regional Research and Training Committee (WPRRTC) to undertake collaborative research and training projects. This initiative was supported by the MS Society of Canada's endMS campaign that identified centers of excellence in MS across Canada. Future studies could include more interested centers. Increasing the number of centers at this time would cause additional delays.

Q: What other projects related to CCSVI are planned by the BC/SASK CCSVI Research Team?

A: The majority of MS research in Canada is funded by the MS Society of Canada which is completely supported by donations. The Canadian Institutes of Health Research (CIHR) is the other major funding agency for research in Canada. BC has submitted an application to the CIHR on March 1st, 2010. If successful we will investigate the role of iron in the brain in CCSVI and MS and we will develop new MRI techniques for the imaging of MS. SASK has also submitted a grant to investigate imaging of iron in the MS brain using a highly specialized and unique Synchrotron technology. The next round of grant applications for the MS Society and CIHR is in September and October of 2010. Those grants would not start until the spring of 2011. Many grants are rejected the first time and need to be rewritten and resubmitted which could delay them by 6 to 12 months. Studies looking at the benefits of treatment could begin after the results of the current diagnostic study are known, depending on available future funding.

FAQs about CCSVI and MS

Q: What are the results of the liberation treatment so far?

A: Dr. Zamboni's study treated 65 MS subjects with different types of MS (35 RRMS, 20 SPMS, 10 PPMS). There was no control group and all patients knew they had the procedure performed ("unblinded"). The doctor assessing them was also aware of the treatment ("unblinded"). 47% had re-stenosis of the vein that was dilated. While this was an important "pilot" study, Dr. Zamboni believes this requires further testing to validate his findings. Since then, several patients have paid for treatment outside of research studies. There is no careful or systematic follow-up of these patients to know how many benefit, how they benefit, what predicts who will benefit and how sustainable the benefit is.

Q: Is the liberation treatment safe?

A: Theoretically, venous dilation alone should be relatively safe. However, in February 2010, it was reported that two patients had serious complications from stents (metal tubes) used in their veins. One patient suffered a fatal blood clot in the brain, while another had to undergo open heart surgery after a jugular vein stent dislodged into her right ventricle. These stents were inserted by one of the top interventional radiologists in the world. The risk with less experienced physicians is unknown.

Q: Could the liberation treatment make MS worse?

A: In Dr. Zamboni's pilot study, based on reviewing his paper, it appears as though some patients had an increase in their MS relapse rate.

Q: What are the results of other research studies?

A: Preliminary results from Dr. Zivadinov at the Jacobs Center in Buffalo demonstrated that approximately 56% of MS patients had abnormalities on ultrasound suspicious for CCSVI but so did 22% of healthy volunteers. This is somewhat different from the 100% rate of abnormality Dr. Zamboni reported in MS patients and 0% in healthy volunteers. It could suggest that CCSVI is less common or less distinct than previously thought. Conversely it could suggest that ultrasound is not accurate enough to detect CCSVI. It does clearly show the importance of independent research in any new medical claim.

Q: My ultrasound said I have CCSVI. What can I do?

A: While this may be accurate, it is also possible that the test is providing a "false positive" result due to lack of standardization and lack of experience. Furthermore, detecting CCSVI would not necessarily lead to immediate treatment until that treatment is proven to be safe and effective.

Q: I want my MRI checked for CCSVI.

A: Most MRI's for the routine monitoring of MS do not include pictures of the veins and would not be suitable for checking for CCSVI. A specialized MRI examination, known as MR venography (MRV) is needed. The BC/SASK CCSVI research project will determine if MRV and ultrasound are sensitive and accurate enough to detect CCSVI.

Q: Can I get tested for CCSVI?

A: The best test for detecting CCSVI is not yet known. We continue to speak with physicians around the world interested in CCSVI, and have come to the conclusion that there remains a lack of standardization on the best way to diagnose CCSVI. The BC/Saskatchewan CCSVI study will answer this question.

Q: Where can CCSVI be treated?

A: Several private and mostly for profit groups are advertising surgical procedures for CCSVI. This treatment in MS is still experimental and we recommend that treatment only occur as part of a clinical trial that includes all of the standard safeguards that are followed in such trials.

Q: If I have the liberation procedure performed overseas, what level of care can I expect from the UBC Hospital MS Clinic?

A: Canadian MS specialists remain committed to providing care to the highest standards possible to all Canadians with MS. We have felt strongly and stated to our patients that while we don't recommend going out of country for experimental surgery for CCSVI, we have and continue to recommend that they return to see their MS specialist for ongoing monitoring and care. Research on CCSVI is well underway in Canada and we can expect important results this year. The best care following a CCSVI procedure is not established and for that reason, approaches may vary across cities and physicians. Nonetheless, patients should be followed by an MS specialist who patients can trust to have the most up to date professional opinion based on evolving evidence on the issues around CCSVI.

Q: How do I know if treatment of CCSVI is part of a research study?

A: You should be given an informed consent form that has been reviewed and approved by an ethics board. The ethics board should be clearly identified on the consent form. In general, there should be no cost or payment for participation in a research study.

Q: Why does more research need to be done?

A: Many of us in the MS clinical and research community watched this story with great interest, but also with some natural skepticism as we have seen similar claims of potential causes and cures in the past. Dr. Zamboni's results are preliminary or "pilot" data that require independent validation. This process of independent validation has been one of the greatest advancements in modern medicine and is crucial for confirming important results and preventing potentially dangerous or useless but costly treatments from being undertaken. Dr. Zamboni agrees that this is an important step that must be undertaken. The many advances in care for MS patients today exist because of this process and the sacrifice made by many volunteers.

Q: How can I support this work?

A: Funding to support this important research will be critical. Donations can be made through the MS Society of Canada, the VGH and UBC Hospital Foundation or the UBC faculty of Medicine.

Q: Where can I get updates?

FAQS on MS Society of Canada-Funded CCSVI Studies

Q: How many Canadian-based grants are you funding and at what value?

A: The MS Society of Canada has funded 4 projects. The total value of all projects is $700,000. Additional research projects will be considered in future research grant competitions administered by the MS Society of Canada.

Q: How were the grants reviewed and selected?

A: All research applications underwent a rigorous expedited peer review process by an independent international review panel that included experts drawn from all key relevant disciplines including: neuroradiology, neurovascular imaging, MS imaging, vascular surgery, biostatistics, interventional radiology, interventional neuroradiology, and MS clinical neurology. The review panel used the Canadian Institutes of Health Research (CIHR) common scale for scoring. The MS Society of Canada and the U.S. National MS Society worked collaboratively to assemble the reviewers who considered scientific merit, responsiveness to the international request for applications, experimental design, likelihood of producing definitive data, and the experience of the applicant teams. The leadership of the Canadian and U.S. MS Societies followed the panel's recommendations and undertook the funding of these studies.

Q: When will recruitment for these studies begin? How can I get involved?

A: Availability to participate in studies will be limited. It's expected that participants will be recruited from existing patient rosters at MS clinics associated with the funded projects. Inclusion in studies may depend on a number of factors including: age, type of MS, geographic location, previous treatment history, patient status at an MS clinic and other medical conditions to name a few. The MS Society of Canada plays no role in selecting participants or determining the process of how participants are selected.

Q: What is the MS Society's role in the research that has been funded?

A: The MS Society's role in this research is as a funder and as such will receive an initial six-month report as well as a one-year interim report from each of the funded studies. The MS Society will post on its website summaries of interim or peer-reviewed results as they become available. Please note, the MS Society of Canada plays no role in selecting individuals to participate in studies.

Q: Will these studies treat CCSVI?

A: These studies are not designed to treat CCSVI but rather to understand the prevalence and significance of the condition as it relates to MS, and to identify the best imaging technology to evaluate it. These are critical steps toward a better understanding of the relationship between CCSVI and MS disease process.

Q: How does this funding relate to the MS Society's request for $10 million from the federal government?

A: The MS Society has committed to advancing this research through the funding of these four research projects. This is in addition to the $8 million the MS Society expended on research during the past fiscal year. The May 5 request to the federal government was made to urge the government to do its part. The MS Society feels strongly that the federal government has a role to play in advancing research on this front as some Canadians have gone overseas and have paid out-of-pocket to get the testing and procedure done in other countries. By funding research on a large scale, the federal government can both advance research and provide safeguards to those seeking diagnostics and treatment.

Q: When will we see results from these studies?

A: The studies are two years in length and researchers expect to publish results in peer reviewed scientific journals as outcomes are established. The timing of data analysis, peer review and publication can vary widely and thus it is not possible to predict when results will be available. However, in addition to a one-year interim report, researchers will be asked to provide an initial 6-month update to the MS Society on their grant progress from the date of funding. The MS Society of Canada will post information as it becomes available.

Q: Why were certain projects not funded?

Projects were assessed by an independent international review panel using the Canadian Institutes of Health Research (CIHR) common scale for scoring. Considerations for not receiving funding might include issues such as research design, feasibility of research proposal, and outcome measurements. See also question 2 for additional factors.

Q: Why are you not releasing details of the applications that were not successful in receiving funding?

A: There is a long and well established convention in the administration of scientific research funding programs that only successful awards are made public. This is a professional courtesy to the investigators who did not get recommended for funding. Researchers who have not been successful in this competition are invited to bring forward applications in subsequent competitions.

Q: When will work begin on these projects?

A: Pending acceptance of awarded grants, it is expected that funds will flow to institutions as early as July 1, 2010. From there, timing will vary by project. Considerations include acquisition of institutional or ethics review board approval, administrative infrastructure and development of recruitment and participation protocols.

Q: What will be the next steps after these studies are completed?

The new projects take a comprehensive look at the structure and function of veins draining the brain and spinal cord in people representing a spectrum of MS types, severities and durations, and compare them to the structure and function of veins in people with other diseases and healthy volunteers. The studies incorporate accepted high standards of experimental blinding and controls designed to provide unbiased results. They also use a variety of imaging technologies including the Doppler ultrasound technology originally used by Dr. Zamboni's team.

Together, these studies aim to further understand the role of CCSVI in MS and identify optimal methods for screening for the condition, which would be necessary to determine the next steps required in advancing this CCSVI lead. They will also be of value in designing protocols for possible therapeutic trials that might be independently undertaken in North America or abroad.