This Is MS Multiple Sclerosis Community: Knowledge & Support

As someone anxious to see CCSVI detection and treatment become more readily available, but does not really struggle with fatigue - I couldn't agree more.

This is brilliant. It will take years to sort through the interplay between CCSVI and MS, but not nearly as long to demonstrate that it improves one major symptom of MS. It is also something that CCSVI seems to work well on, as attested to by Mark. This is a good application of the KISS precept - keep it simple stupid.

When Fampridine was drug trialed, they picked one simple symptom to test - walking speed. They could have tested a wide range of symptoms that chemically improved nerve function could benefit. But why bite off more than you can chew or prove more than you need to.

Focusing on fatigue stands the best chance of making CCSVI treatment widely available. The rest will sort itself out.

Great idea!!

In fact it complements what is already proved. Buffalo trial demonstrated that MS sympthoms are worse for people with CCSVI. Now we only need a clinical trial that shows that fixing CCSVI at least one sympthom (fatigue) dissapears.

With such a proof, it will turn unethical not to test veins in MS patients.

On a second thought, I have just realized the big problem. There cannot be blind controls. A person knows if he-she has been operated. Even with a fake operation they will feel it.

Therefore any study about the effects of vein surgery in colapsed veins will be suspected to be a placebo.

And how are you going to measure fatigue objectively?

You clearly have experience with FDA trials and how they are conducted. I too have had some experience from the company side of clinical trials, and was having a similar thought.

How do we measure fatigue? Is a self-reported fatigue level adequate? It might work if you had an effective placebo so that false subjective improvement would cancel out , but how would you create an effective placebo when the treatrment is an angioplasty or stent?

This is not a cynical nay-saying comment...I really am curious if you can think of something. Since remissions and spontaneous improvements are a typical part of MS and since brain problems are particularly subjective, this strikes me as a difficult problem.

I have PPMS with no relapses and remissions, so there isn't objective to measure. As a result, all the tests and research has been devoted to drugs to reduce relapses since there is something to count and create data to show the FDA, even though the evidence shows that those drugs do not slow progresson very much if at all. Creating measurable data, especially in a resonable time frame, is something I am too painfully aware of.

Hi Fogdweller:

I also was thinking about what could be used as the placebo for the control group. Assuming sham surgery is out, I agree that a simple reporting mechanism by the treated group only will not be persuasive. However, while I'm familiar with the drug approval process, I don't know the limits of clinical trial design.

I was thinking of researching how other trials to assess the efficacy of surgical treatments were done. There must be some, right? Did they use a control group?

What I really want to know is what is required to satisfy the Ontario government that the procedure is no longer experimental. It seems that that threshold is not clearly defined. Once the government lifts the experimental status and agrees to pay for the treatment, I believe no one will be able to stop the vascular surgeons in Ontario from treating CCSVI (assuming that is what is stopping them now).

Fogdweller, I believe that you said you are/were a patent lawyer? I'm a patent agent currently in law school and intend on discussing the scope of "experimental" with a particular law prof at my school as soon as I can hash out the question in my head.

Any other thoughts?

I was thinking about this after I wrote my last post. I think the way you would do it is to treat angioplasty or stents as a treatment for fatigue caused by MS, and compare it head-to-head with the current standard of care or an acceptable drug used as an acceptable treatment. You see this all the time in drug trials .."as effective in treating [fill in the blank] caused by [fill in the blank]". There are a couple drugs that do treat fatigue, and you could compare stents in one leg of the trial and angioplasty in another and the drug in a third and see which is best. If treating CCSVI proves effective or at least as effective as the drug, then there is a medical reason to do it and if t also treats MS in other ways that can be proven later over time.

I really don't think sham surgery is ever ethical, and likely not possible to treat a person in one arm of a study and sham in another and fool the patient in any event.

I have been a patent lawyer for the past 20+ years so if you want to discuss anything about that , I will be glad to talk with you about it. I will send you a pm with my e=mail.

I had the pleasure to confer with an open-minded Doc. today, who had a sheaf of papers - EDDS (I always mix that one - the disability level), etc., but most intriguingly, he had a similar form for fatigue rating. I have asked for a copy of that, as I have read on here about fatigue rating being arbitrary/ too subjective, with no standard. I will post it when I receive it.

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My name is not really Johnson. MSed up since 1993

I find your post very Interesting and going to ask my doc about it, can you explain it a little? T3-T4? I have soft symptoms of MS had few MRI'S done showing leisons but also was Dyagnosed Hypo Thyroid In Sept. Been feeling alot better but Having major exhaustion lately and thinking like your self maybe Its Thyroid still bothering me. I know last few blood tests He said "were in the ball park" but he did have to lower my daily dose a little. I take LEVO daily but to my limited knowledge not alot else you can take? But to check your T3/T4 thats a Blood test Im sure, how do they treat the T'S sorry If this sounds stupid just your post kinda grabbed me! Thanks Doug

Look at this:

http://clinicaltrials.gov/ct2/show/NCT0 ... svi&rank=1

"The evaluation of safety will be defined as the incidence of major adverse events at 30 days following the index procedure. The evaluation of feasibility and efficacy will be determined by those patients that do not have more than 50 percent restenosis within the 30 day time frame."

OMG - does this mean what I think it means? They will be evaluating for safety AND efficacy at 30 days as a primary outcome measure? If the procedure is sufficiently efficacious at this point, it is then unethical to not treat patients, correct? Somebody who has been following clinical trial study designs pinch me please!

This could be great news since symptoms such as fatigue, cold extremities, spasticity, etc seem to be alleviated in that time frame...

That does seem like great news and a very short time period. Much better than the two-year studies!

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"However, the truth in science ultimately emerges, although sometimes it takes a very long time," Arthur Silverstein, Autoimmunity: A History of the Early Struggle for Recognition

Wow, it looks like they think if you're going to re-stenose, it's going to happen within 30 days. I've been wondering about that. It's great if you can know that soon so you don't have to wait around a year wondering if your veins are still open or not.

When I had the Doppler US, the doc said that there were a lot of collaterals coming from my (enlarged, if I recall - engorged?) thyroid. I'm not much up on thyroid issues, but I have been taking elemental iodine for the last year, or so, and my un-ending exacerbation has been about the same length of time.

I was also doing massive doses of nattokinase, rutin, serrapaptase, bromelain, etc., but stopped that 6 months ago because I thought it must be scouring the fibrin plaques in the brain, and letting the breaches in the BBB open again.

Doctor, quack thyself...

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My name is not really Johnson. MSed up since 1993

I understood it to mean that they will look at efficacy for those that didn't restenose by that time - which is great to eliminate poor efficacy caused which may be caused by restenosis.

I don't thinbk so. First of all, the effacy measure is that there is not 50% restenosis within 6 months. This means that there may be NO measure of fatigue, spacticity etc. If you are not restenosed, then the procedure will be deemed efficatious. If stenosis is, in and of itself considered something to treat, then it would be unethical not to provide the treatment. However, I don't think stenosis is a condition that requires treatment, without some evidence that stenosis causes symptoms. That is a step which has not be scientifically proven yet.

Another note of caution. My reading is that the protocol of the study is a proposal, not yet an approved protocol by the FDA or any hospital. I may be wrong on that but I don't see it. Also, I don't see any indication of funding yet. If it is proposed (to start in April no less) but noone pays for it and no hospital approves doing it (only Stanford was doing the procedure and they pulled the plug) and it doesn't generate any data on the effect on MS and its symptoms, then it may not even happen and this may not be as exciting as it sounds.

A bit of a wet blanket, I know, but these are the questions I ask myself when I read something like this.