BNAC commn.

[Lyon]

.

[NHE]

I don't see a problem in discussing the benefits, or potential lack thereof, of sham trials for CCSVI. The problems that I have with it are that there are so many different procedures, large diameter balloons vs. small, cutting balloons, stents, etc. that there currently is no one best method that can be tested. To rely upon one study using one method to judge CCSVI in totality would be myopic at best. In addition, perhaps even a bigger problem with sham treatment is that if you put a catheter into someone's vein, you may be inadvertently clearing out webs and septa that could be contributing to CCSVI even without inflating a balloon. For such a sham procedure to have any validity, the catheter would have to be kept out of any problematic veins such as the azygos and internal jugulars. Lastly, why must CCSVI be forever linked to MS? If people have problems with their veins, should they not be allowed to get them treated independent of whatever effect it might have on their MS? Cinical trials could then be seen as investigating any of the various separate questions regarding CCSVI and its relationship to MS. An analogous situation might exist with dietary supplements. For example, no one prevents me from going into a supplement store and buying and consuming some r-lipoic acid just because I have MS even though research is still ongoing with regards to the benefit of r-lipoic acid and MS.

NHE

[CenterOfGravity]

NHE, I had been thinking about the same thing. To quote Dr. Sclafani from his Q&A thread:

"So as we explore, we find that the permutations of vascular anomalies are many. While we have simple answers to some of these anomalies and are moving toward refined methods of treatment, for others we remain novice. How to deal with vertebral vein problems is more complex and will await further thought.

It is a challenging and fascinating time for CCSVI. With a sham procedure vs. a real procedure, we don't even know yet what is the best procedure for the real procedure. So what are we comparing to the sham procedure? I do think it is necessary to do these blinded studies, and as long as we also remember that there is also much to learn about what are all the problems and different solutions. Are the studies using the bigger balloons and breaking open the valve problems that Dr. Sclafani discussed? And like NHE said, what if just putting the catheter in can have some effect, like breaking webs or whatever. I do highly believe CCSVI and MS have a significant relationship, and that relationship is only 1 small part of what needs to be studied. It will also take time to figure out what is the best way to treat the wide variation of venous anomalies, and to somewhat "standardize" the treatment. I wish I had a crystal ball to see 5 years out, because I bet there will be lots and lots of answers, and treatment (both initial and ongoing if necessary) will be standard and covered by insurance everywhere, even in Canada!

[MarkW]

I am astounded at concerned's suggestion of anesthsia. In the UK a trial ethics committee would never approve of anesthesia simply to blind patients in a trial. Anesthesia carries greater risk than balloon angioplasty of arteries so is unethical in a trial which does not need it to treat the patient.
so concerned please explain how to blind patients in an ethical way.

MarkW
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MarkW wrote:
If those posters who demand placebo controlled double blind clinical trials could explain the design of such a trial, including the design of a sham arm. Then I will accept you are challenging from a position of logic. Otherwise like many surgical procedures I asert that a drug style clinical trial is impossible (not a gold standard).

Concerned replied: One word: anesthesia.
Like other surgical procedures, a placebo controlled double-blind clinical trial is very possible, and furthermore, desirable.

MarkW asks: Please explain the trial design of this 'very possible' trial.
-----------------------

[MarkW]

There is a lot of work required on diagnosis and de-stenosis before a definitive clinical trial could be designed.

NHE wrote:
The problems that I have with it are that there are so many different procedures, large diameter balloons vs. small, cutting balloons, stents, etc. that there currently is no one best method that can be tested.

This is in fact trial design problem three ! The first design problem is an agreed list of which veins may be restricted (rather basic this !). Design problem two is the the type of restriction which may be encountered and how to diagnose it (see Prof Sclafani's recent paper for details).

The way this normally works is for medical rsearchers to conduct case studies to answer the three initial questions:
1 - which veins may be restricted
2 - types of restriction and diagnosis method
3 - best methodology (types, pressures, sizes and duration of balloons).

This work is going on and you could hear some of the discussions at Prof Sclafani's NY seminar. Large balloons were mentioned, also high pressure.

Provided pwMS understand the risks they are taking by using balloon venoplasty (mainly the need to repeat the procedure later on, in my opinion). Then why do MS neuros and naysayers have the right to block treatment of CCSVI syndrome until clinical trials are complete ???

I repeat my challenge: Propose a design for a double blind placebo controlled trial with a sham arm (which is ethical).

MarkW

[concerned]

MarkW asks: Please explain the trial design of this 'very possible' trial.
-----------------------

I'm not a medical researcher, so I cannot explain the design of the trials underway in Albany, Stanford, Ferrara, etc.

It would probably best to ask one of those CCSVI docs that are performing the trials.

Performing sham surgeries under general anesthesia is a controversial topic, but I don't see how, with informed consent, it could be so easily deemed unethical.

If you don't believe it could be done, look up "sham surgeries under general anesthesia" on google.

[MarkW]

MarkW asks: Please explain the trial design of this 'very possible' trial.

Concerned replies: I'm not a medical researcher, so I cannot explain the design of the trials underway in Albany, Stanford, Ferrara, etc.

MarkW comments: So a naysayer says I can't explain the trial design but I know it is 'very possible'. You are simply wrong Concerned. A double blind placebo controlled trial with a sham arm is very difficult to perform. My view is that it is impossible at this stage of research of CCSVI syndrome.

Concerned wrote: Performing sham surgeries under general anesthesia is a controversial topic, but I don't see how, with informed consent, it could be so easily deemed unethical.

MarkW replies: A trial must not place the trial subjects at any risk than absolutely necessary. General anesthesia is a significant risk which is not required for balloon venoplasty so in the UK would be considered unethical in a trial design.

Concerned wrote: If you don't believe it could be done, look up "sham surgeries under general anesthesia" on google.

It did not say it was impossible but unethical. Even a paper (1) which argues for sham surgery starts with (2)

(1) http://www.springerlink.com/content/e25u62j75tl27001/
(2) Surgical clinical trials have seldom used a “sham” or placebo surgical procedure as a control, owing to ethical concerns. Recently, several ethical commentators have argued that sham surgery is either inherently or presumptively unethical.

Sham venoplasty is unethical at this stage of the research and is in my view impossible to perform on conscious patients.

MarkW

[concerned]

So your position then is that Zamboni et al are an unethical lot then?


I don't get it.

Is medical tourism for an unproven treatment ethical?(Zamboni doesn't think so) What is ethical, and how is it measured?

[MarkW]

You need to try harder Concerned if you want to trap me...MarkW

Concerned wrote:
So your position then is that Zamboni et al are an unethical lot then?
I don't get it.
Is medical tourism for an unproven treatment ethical?(Zamboni doesn't think so) What is ethical, and how is it measured?

MarkW comments: Genuine information seekers should remember that Prof Zamboni was heavily critised for his initial studies which MS neuros and naysayers said where lacking in controls. Now the naysayers demand double blind placebo controlled trials with a sham arm and will not listen when they are informed such a trial is not possible at this stage of research.

Balloon venoplasty is a safe effective treatment to de-stenose restricted veins, which are found in CCSVI syndrome. The naysayers stretch the comments published by Prof Zamboni, I wonder why.

MarkW

[scorpion]

You need to try harder Concerned if you want to trap me...MarkW

Concerned wrote:
So your position then is that Zamboni et al are an unethical lot then?
I don't get it.
Is medical tourism for an unproven treatment ethical?(Zamboni doesn't think so) What is ethical, and how is it measured?

MarkW comments: Genuine information seekers should remember that Prof Zamboni was heavily critised for his initial studies which MS neuros and naysayers said where lacking in controls. Now the naysayers demand double blind placebo controlled trials with a sham arm and will not listen when they are informed such a trial is not possible at this stage of research.

Balloon venoplasty is a safe effective treatment to de-stenose restricted veins, which are found in CCSVI syndrome. The naysayers stretch the comments published by Prof Zamboni, I wonder why.

MarkW

It was not that people were SAYING Zamboni's initial studies were lacking controls they actually were lacking controls. I am not demanding anything but there would be a heck of a lot more people willing to listen to Zamboni's ideas and if the trials confirmed CCSVI more people would be willing to give money CCSVI research. I think there will be double blinded studies and I am waiting anxiously for the results!

[malden]

There is no need for controls or MS patients for testing a "CCSVI facts":

CCSVI, Just the facts, ma’am

1. What is CCSVI?

Chronic cerebrospinal venous insufficiency... it’s a chronic (ongoing) problem where blood from the brain and spine has trouble getting back to the heart. It’s caused by stenosis (a narrowing) in the veins that drain the spine and brain. Blood takes longer to get back to the heart, and it can reflux back into the brain and spine or cause edema and leakage of red blood cells and fluids into the delicate tissue of the brain and spine. Blood that stays in the brain too long creates “slowed perfusion”...a delay in deoxyginated blood leaving the head. This can cause a lack of oxygen (hypoxia) in the brain. Plasma and iron from blood deposited in the brain tissue are also very damaging.
...

But are these the facts?
Unfortunately not. Those are, so far, unproven hypotheses which underlie the whole MS-CCSVI theory and treatments based on Liberation procedure.

Take a healty person, put it on MR, make quantified blood flow meassurements, then induct the stenosis (a narrowing) in the one vein that drain brain by applying outside preasure on the neck on the vein spot, make blood flow meassurements again and compare results (time, flow, etc).

Then you will have a good starting points for the answers:

Does blood takes longer to get back to the heart after vein narrowing?
Does blood reflux back into the brain after vein narrowing?
Does blood stays in the brain too long after vein narrowing?
Is a delay in deoxygenated blood leaving the head after vein narrowing?

Simple, isn't it? No cutting, no sham, no procedure at all, no subjective influence... Just objective measurements.

Maybe to simple for someone big appetite ;)

[CCSVIhusband]

NO healthy person with good blood-flow is going to allow something to restrict their veins ... is that a serious statement? Really?

That's just INSANE ...

I can't imagine ANYONE would do that.

[Cece]

What Malden is suggesting is an acute obstruction of one jugular. CCSVI is a chronic obstruction of both jugulars or a jugular and an azygous or an azygous and the verts or any combination thereof.

Acute obstructions are already understood and treated, i.e. thrombosis. They also usually occur in just one vein, not multiple veins.

[malden]

CCSVI is a chronic obstruction of both jugulars or a jugular and an azygous or an azygous and the verts or any combination thereof.
....

Ok, then make an acute obstruction on both jugulars. No big deal. Just apply light outside preasure on the neck on the veins spot.
And I don't mean to strangle person, just to induce short, temporal narrowing, in the limits (30%, 50%, 60%....?) already founded in Liberated patients. Not harm at all.

I did not mention testing CCSVI theory per se, just un unproven hypotheses which underlie the MS-CCSVI theory:
- blood takes longer to get back to the heart because of vain(s) narrowing,
- blood reflux back into the brain because of vain(s) narrowing,
- blood stays in the brain too long because of vain(s) narrowing,
- delay in deoxygenated blood leaving the head because of vain(s) narrowing.

A simple matter.

[Cece]

I think, in the trial sign-up or in the IRB application, we should be sure to include the phrase, "We don't mean to strangle people."