We can learn a lot by digging into the details of Dr. Zamboni’s Italy-wide study set to launch next month.
Purpose
“To assess in a double blinded randomized control trial (RCT) study design safety and effectiveness of balloon angioplasty of the main extracranial and extravertebral veins in multiple sclerosis (MS) associated to chronic cerebrospinal venous insufficiency (CCSVI).”
That hits it right into the ballpark where the Canadian government said they were stalled: safety and efficacy.
It’s also a double blinded randomized trial. With 679 participants (half of them will get a sham procedure: “The patients will undergo catheter venography but not PTA”).
Dr. Zamboni is going right into the dragon’s den with this. He’s not afraid to confront his critics by giving them everything they’ve asked for. Next question is, will it be enough?
Next, this study gets right into it by assessing, well, everything, you could possibly imagine. Actually, Dr. Zamboni must have a pretty good hunch these outcomes are the things most likely to respond to angioplasty or he wouldn’t be wasting his time measuring them. Here’s the list of parameters that will be assessed every three months (hey Canada, this is how to do a CCSVI registry!):
A) Dynamic Balance Assessment: Balance Master Limits of Stability (LOS). In static platform, swinging to reach the set position of center of pressure.
B) Static Balance Assessment: Balance Master Limits of Stability (LOS). In static platform, the subject keeps the balance contrasting various forms of disturbance of visual and proprioceptive sensory feedback.
C) Walking Function: The subject walks spontaneously for 10 meters with chronometric measure of time counting the number of steps. The test calculates the walk ratio i.e. ratio between length and step frequency.
D) Manual dexterity. Box & Block test, moving wooden cubes.
E) Sphincter control: Post-voiding residual by ultrasounds.
F) Visual acuity: Low-contrast visual acuity Sloan Letter Chart.
Then, Dr. Zamboni assesses his subjects through MRI:
Magnetic Resonance Imaging (MRI) outcome measures: T1Gad active lesion.T2 lesion volume MRI evaluation at baseline, 6, 12 months.
Dr. Zamboni is also tracking:
Chronic fatigue. This highly disabling symptom completely orphan of effective therapy will be measured by M-FIS (Modified-Fatigue Impact Scale).
Cognitive function. Cognitive functions will be measured by the means of MoCA mental state questionnaire.
Annualized relapse rate. In the sub population affected by the RR clinical form the number of relapse will be assessed.
Patency rate. The rate of successful PTA will be assessed by the means of postoperative Doppler sonography.
Emotional status. Anxiety and Depression Scale for use with multiple sclerosis patients will be administered.
Memory and cognition. The assessment will be performed by the means of PASAT - Paced Auditory Serial Addition Test
Overactive Bladder. Overactive Bladder symptom will be measured by the means of validated Overactive Bladder Questionnaire-b.
For us, there’s both good and bad news for what might eventually come to Canada in the documents filed with clinicaltrials.gov.
Inclusion Criteria:
•patients affected by CCSVI associated with MS
•relapsing-remitting and\or secondary progressive
•18-65 years old
•EDSS 2-5
•disease duration < 10y
•No relapse in the 30 days preceding the procedure
•clinical stability in the last 6 months with disease mod. treatments
•Patients under the best available therapy
Note, individuals with primary progressive are left off the list. As are people with EDSS > 5 or lower than 2.
Disease duration<10y, sounds like total number of years with symptoms, not since diagnosis. If so, a disease duration of fewer than 10 years will exclude a lot of people.
Lastly, it sounds like not only do they want individuals on DMDs, they want them to stay on the DMDs. (Although I would argue a diet is the best available therapy if I was eligible to join!).
These inclusion and exclusion criteria set the stage for how this will be used to shape eventual government policy, in my opinion. I think governments are dreading having to treat everyone with MS: if Zamboni’s study shows angioplasty is a safe and effective treatment, governments can argue it’s only safe for people diagnosed with RR and SP multiple sclerosis of fewer than 10 years duration…
It will be a way to cut the numbers down of how many are added to wait lists. For everyone outside that small group, they will likely be told there’s no research showing it’s safe and effective for you.
That’s why we need more research to start ASAP and test people with all forms of MS with lengthier duration! Please include this information when making your case for Canadian trials. Canada (or any province) will approve treatment only for people similar to those they included in any clinical trials.
Full study details at Clinicaltrials.gov: http://clinicaltrials.gov/ct2/show/NCT01371760
Dr. Zamboni's research site (accepting donations!): http://bravedreams.ccsvi-sm.org/
http://www.facebook.com/notes/ccsvi-at-ubc-ms-clinic-information-and-support/dr-zambonis-ccsvi-study-brave-dreams-brain-venous-drainage-exploited-against-mul/10150208866387734
