PREMiSe study results

[ThisIsMA]

Cece said:

ThisIsMA, what do you think about this? https://scopeblog.stanford.edu/2012/07/ ... -medicine/
"medstartr" and "IAMScientist" for crowdfunding medical research. Maybe this is what we need?

I think you are an excellent researcher!

I didn't realize that Kickstarter doesn't fund medical research. I read the link you sent and both of those other startups sound promising. The next step would be to research reviews of the two sites, find out if either has been successful in raising money for a scientific research project. Also check to see which is more user friendly for the non-technically inclined.

[MrSuccess]

Hi ThisIsMA - I certainly do not have any problem with anyone who disagrees with my opinions. I welcome the challenge. How else can we learn ?

Optimist ? Ummm .... I think " realist " might be a better description.

In 2008 , Professor Zamboni published his study findings. A small 65 patient research he conducted to see if his hunch , that pwMS , MIGHT ..... have blood flow problems ... in the neck and chest . He treated those patients for a condition he coined .... CCSVI.

It certainly is worthwhile to read what transformed in that 65 patient study. It caused quite a stir in the Neurology field . They take the position that MS is an electrical problem . Dr.Zamboni suggested the problem was .... faulty plumbing .

Dr.Zamboni challenged his peers to replicate his 65 person CCSVI study . And many have risen to the challenge ..... because .... it just makes sense.

Including the University of Buffalo [ Jacobs .. ] . Someone posted here at TIMS that the U of B have produced 25 papers on CCSVI so far .... Am I right ?

The last one being , the PREMISE study of [ 30? ] pwMS .... suspected of having CCSVI.

This small Trial will be REJECTED by those opposed to CCSVI [ some Neurologists ..... Big Pharma ] as to accept it .... is to accept that CCSVI even exists ...... and that the CCSVI procedure is SAFE. The next step is publication in respected Neurology journals and presentations at respected Neurology conferences. Expect STRONG resistance .

I found Ringleaders last post ..... informative . Read it carefully .



Come Watson ! The Games afoot !


MrSuccess

[dania]

In my opinion and from personnel experience I believe CCSVI is only part of the equation. In my case my Atlas is out of alignment. And I now realize it has been out of alignment for a very long time. More than 50 years. And looking back I now see signs, way back before I was a teenager, of the start of my disability which I did not recognize before. Having been one of the fortunate ones that has been in Dr Scott Rosa's study, he performed 3 upright Fonar MRI's which showed my CSF is not draining adequately from my brain. When Dr Rosa adjusted my Atlas, putting it back in alignment, and a MRI showed much improved CSF flow. I had improvements just as I had with angioplasty. Unfortunately I have not been able to keep the adjustment. In my case, I believe it is the lack of proper CSF flow that caused stenosis of my veins. Even the vein (healthy saphenous vein) that was put in with my bypass operation closed/stenosed completely. It will be interesting when Dr Rosa's study is completed and published. I believe for many of us it is impaired CSF flow which in time does affect flood flow. In my opinion CCSVI is not the cause although it is a consequence.

[Jugular]

If altering cerebral blood flow caused an increase in disease activity in the form of brain lesions, doesn't that also show that there is a link between MS and cerebral blood flow? This finding goes against the convention model of MS and itself warrants further research. I would think that some researchers out there would react by saying "that's interesting" instead of "that's unexpected".

[1eye]

About all this drastically under-powered study does is prove you can't treat a serious illness with placebo. Cochrane has been saying that for years. Proves CCSVI exists, and is a problem certain people sometimes can't fix. Ain't gonna stop me. Further study is warranted,

[MrSuccess]

A good many things have been learned from the very interesting PREMISE study.

Best of all ..... another 30 pwMS have undergone the CCSVI treatment. We now can follow the course of health improvements ..... or not. The story certainly does not stop at the conclusion of the Trial. In fact ... I think it actually begins. I'm sure they will all be monitored for years to come.

As pointed out in a post above ^^^^^^ ...... there is conflicting information about the effectiveness of CCSVI treatment , presented by the SAME source . I think I " get it " I would NOT be surprised to read that a good many of the PREMISE patients are doing very well ...... six months from now.

The PREMISE study was a Clinical Trial. Double - Blinded . I believe DB means .... that both the participants [ pwMS ] and the medical professionals involved ..... had no prior knowledge of who got treated for CCSVI .... or who got the Placebo treatment.

Eventually , ALL of the Trial participants recieved the CCSVI treatment. Or so we are told.

I like that the Trial was run by Neurologists . Dr.Z . Dr. B-WS. Two respected scientists.
I like that the PREMISE Trial concludes that CCSVI .... is a PROVEN medical condition.
I like that the PREMISE Trial concludes that treating CCSVI is SAFE , in Clinical Trials.
I want the PREMISE Clinical Trial results .... to be PUBLISHED .... in Neurologist Journals.
I want the PREMISE C T results ..... discussed at length .... at their Neuro Conferences.

For the last FIVE years the Neurological World has gone from stone silence to contept to ridicule of Professor Zamboni's discovery of CCSVI and it's relationship to MS and other Neurological conditions. As story's of patients getting CCSVI treatment surfaced , and some reported significant improvements in MS symptoms , questions of safety [ I agree 100 % with the Neurologists ] surfaced. I think this can now be put to rest. IT is SAFE.

I for one , think anything worth being tested or trialed , should at LEAST have 100 participants. As it makes the math easier. The PREMISE Trial was indeed , minimal.

The NMSS should now fund a larger - 1000 pwMS - CCSVI Trial . Forget the placebo part of the package. Get on with the Big Picture. It EXISTS and it's SAFE.

Once again the grassroots pwMS should exert pressure on the NMSS to spend the funding collected by pwMS interested in CCSVI ....... on a FULL and LARGE .... CCSVI Trial.

After all ..... it is YOUR money not theirs.

I nominate Dr.Hubbard to oversee and hire the right people.




Real Eyes Realize Real Lies


MrSuccess

[Cece]

The NMSS should now fund a larger - 1000 pwMS - CCSVI Trial

I agree completely, especially given Dr. Tucker's explanation of margin of error that gives a reason for why we'd want a 1000 patient trial. The randomized/blinded portion is necessary, imo, because that helps the results get accepted by other medical doctors. If it's a randomized trial, it's class 1 evidence.

Unfortunately though even if the NMSS should fund a larger trial, they are looking at fairly negative results from the studies so far, and that may be a basis for a decision to not fund this any further.

I am still very encouraged about the effectiveness of ccsvi venoplasty in at the least a subset of MS patients (it worked for me) but I am absolutely discouraged at the slow progress of the research and the negative results and the huge need that exists in the MS population for any treatment that works.

[MrSuccess]

before anyone get's out of line with poor old MrSuccess , I have to call on my CCSVI experts , to tell me ...... How many people participated in the PREMISE Trial ?

I thought it was 30 . Was it 30 or 20 ?

Either way ..... more science to examine. And that's always a good thing.

MrSuccess is of the opinion that the ' fly in the ointment ' in ANY Trial or treatment involving pwMS ..... are DISEASE MODIFYING DRUGS . Also known as ...DMD's.

As can be expected ..... those that believe in the THEORY that MS is a situation wherein the body's own immune system is attacking itself ..... also believe that DMD's help.

Correct me if I'm wrong .... but is it not true that virtually each and every pwMS that has undergone treatment for CCSVI ..... are already taking DMD's ? Can the improvement in MS symptoms not be a result of the DMD's ? I don't think so , but many will think this as so.

It cannot be proven either way . Or can it ?

MrSuccess suggests that a small CCSVI CLINICAL TRIAL involving pwMS that have NEVER TAKEN any DMD's ..... . Thus eliminating DMD's as the cause for any improvements after treatment.

And for the record : MrSuccess stands firm in his belief that pwMS CAN benefit from having their CCSVI treated . Far and away , too much positive evidence to ignore. The goal is to somehow get this treatment mainstream , and easily affordable.




MrSuccess

[Cece]

before anyone get's out of line with poor old MrSuccess , I have to call on my CCSVI experts , to tell me ...... How many people participated in the PREMISE Trial ?

I thought it was 30 . Was it 30 or 20 ?

Sadly it was 9 treated in the actual blinded portion of the trial.

10 were initially treated openly, and not included in the blinded portion.
10 were shammed.
10 were supposed to be treated but 1 was not found to have any stenoses, so only 9 were treated.

[MrSuccess]

thanks Cece - so Nine only ? Nine treated and 10 faked ?

I look forward to reading the whole Trial results. At first blush the size of the Trial numbers could be easily skewed.

I guess it's a start in the right direction ........

I'd like to suggest another benchmark MS scientific test. Snatch 100 Neurologists off the street. MRI their heads . Count the brain lesions. Ask them if THEY have MS. Ask them if THEY are healthy. Truth is MOST medical professionals have never been inside an MRI in their life. Never had their heads MRI'd.

I guarantee you ...... CCSVI treatment will happen overnight ...... when they see their MRI results.

That's Human Nature ...... the trick is to make a great idea ..... theirs.



MrSuccess

[Cece]

I look forward to reading the whole Trial results. At first blush the size of the Trial numbers could be easily skewed.

Yeah, when they say it's a small trial, it's a very very small trial.
But I can't imagine what the expense would be of a 1000 person trial to get the margin of error mentioned earlier.
I am trying to think through what it might mean that MS might worsen slightly in the early months after ccsvi venoplasty. I've read this today from Dr. Zivadinov:

"When you reopened those veins in the neck, I think something happened in reperfusing the brain and re-exacerbating disease activity. The message of this is clear. The majority of patients who are relapsing-remitting should not undergo this treatment," he said in an interview.[/quote

"We chose very active patients who had one relapse in the previous year or [gadolinium-] enhancing lesions in the 3 months before. The sample size is small, but [more than half] of patients in the treatment group showed increased activity," Dr. Zivadinov said.

http://www.clinicalpsychiatrynews.com/n ... 50d27.html
More than half means at least five of the nine treated patients had worse MS activity. Dr. Zivadinov mentions reperfusion, and that is something we have discussed before!

Major finding: A total of 19 new contrast-enhancing MRI lesions were observed in 9 "liberation therapy" MS patients within 6 months of treatment, compared with 3 lesions in 10 control patients.

[Cece]

The majority of the subjects were women. On average, they were about 45 years old, had been diagnosed with MS for 11 years, and were mildly to moderately disabled (mean EDSS score about 4). Most were on interferon, glatiramer acetate, or both.

More information on the PREMiSe patients, from the article linked above.

Venous angioplasty didn’t cause any serious complications, and it restored venous outflow to at least 50% of normal in most patients. Phase I patients had a better than 75% improvement overall. Phase II patients had less benefit; there were no differences in venous hemodynamic insufficiency scores between treated and sham patients.

The first ten patients, treated openly before the sham trial began, fared better than the nine patients in the trial. Luck of the draw.

The treatment "failed to provide any sustained improvement in venous outflow as measured through duplex and/or clinical and MRI outcomes," and "more sizable changes in venous outflow [were] associated with increased disease activity primarily noted on MRI," Dr. Zivadinov and his colleagues concluded.

Ok while this is definitely opposite world where that is the opposite effect than what was expected, it is indeed an effect.

Based on this, should patients either get on DMDs or remain on DMDs prior to the procedure, and have a relationship in place with a neurologist to treat any possible flare-ups resulting from the procedure? If the flare-ups are due to reperfusion, and reperfusion means restored blood flow, I am still convinced that restored blood flow is a good thing in the long-term. But I am equally convinced that we may need to be cautious in the short-term especially in the early months after the procedure, since this study suggests that MS disease activity might actually worsen during this time.

[MrSuccess]

we now have more CCSVI science to debate and explore. And that is fantastic news.
The PREMISE study was small. Smaller than I originally thought. Obviously my call for a 1000 person CCSVI Trial is ..... wishful thinking on my part. I'll be more than happy with 100.

Let me design the Trial :

ALL participants recieve 3 UPRIGHT MRI's ..... before treatment , post treatment , and exactly ONE year after.

All participants recieve neck collar blood flow measurements before treatment , post treatment , and exactly ONE year after.

All participants will be treated using IVUS .

The Trial will be 70 female and 30 male.

The Trial will be equally divided into the 3 main MS groups.

ALL medical and clerical researchers MUST also have an UPRIGHT MRI and Neck Collar blood flow test.

Most important of all ....... 10 of the participants must have NEVER used DMD's .

Apart from IVUS ...... the cost should be affordable .

I again nominate ..... Dr.Hubbard to conduct my CCSVI Trial.




MrSuccess

[MarkW]

I am not surprised by these results as the trial did not diaganose all stenoses and only treated stenoses in some areas (neck?). It is not trial size which is the problem but trial methodology.
All I have learnt from this report is that you need to find a clinic which uses catheter venography (CV) and intravascular ultrasound (IVUS) to investigate all major veins outside the skull. All stenoses need to be fully de-stenosed and blood flow checked a month after the procedure. I have said (along with some others) that CV and IVUS are requirements for diagnosis. Sadly the Buffalo Premise study used a sub-optimal diagnosis methodology and then failed to treat all veins.
Cece you and I are in a small group who were diagnosed and treated by an expert vein plumber. We can testify to the long term benefits of a full de-stenosis procedure. Many others have spent their savings on sup-optimal procedures, very sad.
MarkW

Subjects in this study were chosen using noninvasive imaging, but the diagnosis of CCSVI was confirmed during catheter venography using IVUS. The treated veins were the Internal Jugulars and the Azygous. BNAC did use the optimum diagnostic technology, and also used what is considered to be the standard CCSVI treatment protocol.
The most disturbing finding in this study was that the treated subjects faired worse than the sham subjects. Of course, this was a small study, and as the researchers explicitly state, further study is absolutely necessary.
Here's a link to the short video featuring the two lead researchers:

There certainly is still a lot left to learn… So much potentially vital information has been lost due to the lack of long-term tracking of CCSVI treatment patients. Of the 30,000 patients treated, we only know the outcomes of a tiny percentage. It's really a shame…

Hello Marc,
So I am clear in my comments on BNAC. CV and IVUS must be used in combination and a complete range of veins must be investigated in order to say that CCSVI syndrome is present or not. So I repeat BNAC did not use a full trial methodology. Put plainly its not just the tools used but also which veins are investigated.
Cece has already said that you must show that the treatment used reverses CCSVI syndrome. I did not hear that BNAC did this. The real shame of the BNAC trial is that someone like me can detect defects in the trial methodolgy, without even having to read the detailed method. I am totally unconvinced that blinded trials are possible at this time because no one is sure where to look for stenoses, most ThisIsMSers know that investigating 3 veins is not sufficient. Also there is no standard protocol for treating stenoses found. Each interventionalist seems to use a different method.
I wish that BNAC and others would undertake open trials and answer the questions:
Which veins may have stenoses?
What is an effective procedure to treat stenoses?
The BNAC group appear to have conducted a drug trial. They seem to have forgotten the work done by the pharma co before a trial starts (phases one and two) and gone straight to phase three in their trial design.
Apologies for my delayed comments,
Kind regards,
MarkW

[MrSuccess]

As pointed out ...... BNAC has provided conflicting end results. For those in the vascular camp ...... positive results . And for the Autoimmune camp ..... negitive results.

Take your pick.

MrSuccess has lived his entire life on the principle of ' MEASURED RESULTS ' as oppossed to OPINIONS . For example : Do Not tell me it is cold outside. SHOW ME a thermometer.

What might be cold to you ..... may seem mild to me.

The Neurological world has various tests they use to aid them in diagnosing pwMS.

Some are ...... memory tests . timed 25 foot walking tests . other things. However , there is NO TEST that I know of that proves that you have MS. HEALTHY people are known to have brain lesions . This is a FACT. The good old 'Go-To' .... blood workups .... prove nothing. Same thing with spinal fluids ...... they can be anything other than MS. Lyme?

Any future Trials that involve the relationship of CCSVI to MS ..... MUST .... feature MEASURED RESULTS . Dr.Zamboni's neck collar invention could be a big player. This invention coupled with inexpensive upright MRI's , seem the way forward.

Throw in biodegradable stents ..... IVUS ....... the future of MS treatment is looking awfully good.


MrSuccess