Tuesday, 1 July 2014

CCSVI trial reports no benefit

#MSResearch CCSVI trial shows no evidence of action

Epub: Siddiqui et al. Prospective randomized trial of venous angioplasty in MS (PREMiSe). Neurology. 2014 Jun 27. pii: 10.1212/WNL.0000000000000638.

OBJECTIVE: We report the results of the investigation of safety and efficacy of venous angioplasty in patients with multiple sclerosis (MS) with findings of extracranial venous anomalies, considered hallmarks of chronic cerebrospinal venous insufficiency (CCSVI), in a 2-phase study (ClinicalTrials.gov NCT01450072).

METHODS: Phase 1 was an open-label safety study (10 patients); phase 2 was sham-controlled, randomized, and double-blind (10 sham procedure, 9 treated). All study patients fulfilled venous hemodynamic screening criteria indicative of CCSVI. Assessment was at 1, 3, and 6 months postprocedure with MRI, clinical, and hemodynamic outcomes. Primary endpoints were safety at 24 hours and 1 month, venous outflow restoration >75% at 1 month, and effect of angioplasty on new lesion activity and relapse rate over 6 months. Secondary endpoints included changes in disability, brain volume, cognitive tests, and quality of life.

RESULTS: No perioperative complications were noted; however, one patient with history of syncope was diagnosed with episodic bradycardia requiring placement of a pacemaker before discharge. Doppler evidence-based venous haemodynamic insufficiency severity score (VHISS) was reduced >75% compared to baseline in phase 1 (at 1 month) but not phase 2. In phase 2, higher MRI activity (cumulative number of new contrast-enhancing lesions [19 vs 3, p = 0.062] and new T2 lesions [17 vs 3, p = 0.066]) and relapse activity (4 vs 1, p = 0.389) were identified as nonsignificant trends in the treated vs sham arm over 6 months. Using analysis of covariance, significant cumulative new T2 lesions were related to larger VHISS decrease (p = 0.028) and angioplasty (p = 0.01) over the follow-up. No differences in other endpoints were detected.

CONCLUSION: Venous angioplasty is not an effective treatment for MS over the short term and may exacerbate underlying disease activity.

CLASSIFICATION OF EVIDENCE: This is a Class I study demonstrating that clinical and imaging outcomes are no better or worse in patients with MS identified with venous outflow restriction who receive venous angioplasty compared to sham controls who do not receive angioplasty. This study also includes a Class IV phase 1 study of safety in 10 patients receiving the angioplasty procedure.

              
Time to send the book back to the library for shredding?

Normally we wait until CCSVI saturday to post on all things CCSVI. 

However this is important data. The neurologists appear to be crowing. 

Epub: Bourdette and Cohen. Vennous angioplasty for "CCSVI" in multiple sclerosis: Ending a therapeutic misadventure. Neurology. 2014 Jun 27. pii: 10.1212/WNL.0000000000000651. 

ProfG may comment on this later..he is busy, but at his own risk as any comments seem to bring out the trolls. So when you think about making those abusive comments...take a deep breath and stop it!. Remember we have control of all comments.

In an small study there is no treatment effect. 

If CCSVI was a wonder treatment then it would be seen in all, it was not. In the first arm of the study aspects of CCSVI were reduced, but in the second phase which showed the failure this did not happen. Furthermore there was a trend for disease worsening in terms of MRI/clinical activity in the second phase. However, this was not statistically significant and whilst news has been that this worsens MS, the data is not good enough to show this.

This study was performed by "Pro-CCSVIers".. However it does not prove it does not work..but maybe the writing is on the wall. 

However, it suggests that their are better ways of spending your money.

18 comments:

  1. Do you feel that there are any positives that have come out of the CCSVI experience? It has produced much mudslinging and name calling, emotion locking horns with evidence and considerable time and money being spent on a long list of trials that have failed to reproduce the results of the original study. However, are there any benefits, eg tangential increases in scientific knowledge, sociological insights, awareness of how better to moderate blogs?

    ReplyDelete
    Replies
    1. This blog:-)
      It is clear that neuros need to be in the social media space.
      What is the next fad going to be? How will they react how will the ms societies react?

      Delete
  2. CCSVI gave people hope. This is something that the Neurology community do not offer their patients.
    I am sick of being told my husband will never get better. He is 43,we have a young child and don't have much to look forward to save him becoming more ill. He is losing his walking,he is always tired,and I mean TIRED. He is also losing bits of his memory-dementia anyone?-
    So if CCSVI gave people hope and still does,then good for them. Neurolgists should try the same,or better still, get off your high horses and really look at the suffering of your patients. Then perhaps as a community you will try to help people instead of leaving them vulnerable to trying things-ANYTHING-to get better. People want to get better,I just wish the doctors wanted to help them get better.
    Trying to research something for 100 years and still not coming up with a treatment suggests you need to do something else. Anything else.
    So what if CCSVI has not panned out? It was an avenue worth exploring. The autoimmune nonsense has got nowhere for a lot longer. If anyone is conning MS patients, its the Neurologist who claim to look after them.

    ReplyDelete
    Replies
    1. The autoimmune nonsense has given people 10 licenced treatments and more on the way.
      Was it worth a try....the original reports needed to be repeated but the central problem are the quacks/frauders that prey on people in need. Some have done this serially from one failed fad to the next maybe they need to be reeled in as they often peddle false hope.

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    2. To AnonymousWednesday, July 02, 2014 11:03:00 pm, at what stage did your husband start treatment (if any)? The problem is that too many people choose not to opt for treatment early in the disease and wait until dissability starts to occur. At this point they are dissapointed therapies fail to work at this stage of the diseas3.

      I agree that people in this position (or those with PPMS) might see hope in Lberation treatments just like those with advanced cancer may look to shark cartiledge as a cure. But at this pount any"doctor" such as an interventional radiologist preying on MSers to drum-up business should have their medical license revoked at the minimun.

      Delete
    3. "The autoimmune nonsense has given people 10 licensed treatments and more on the way."
      Hopefully the "more on the way" treatments will not be tweaking the immuno-modulating drugs already available (e.g. PEG interferon). Effective neuro protective drugs are needed. Have the 10 licensed treatments adequately addressed the RR stage?

      Delete
    4. It depends when you start taking them and what you one you use.

      Delete
    5. Sorry that some comments are not being seen, it is not about stifling debate, but we have frankly answered all this stuff before.

      Delete
  3. Ten licenced treatments and none for PPMS. That is what my 43 year old husband suffers from.
    His Consultant doesn't even bother seeing him-why should he? Its not like he can help.
    We have not tried CCSVI. I wish we had though. I would take temporary relief over this barrage of crap we suffer from daily.
    MD, MS,esp PPMS sufferers are left to get on with it with doctors who don't know how to make them
    better. Failure is accepted by doctors dealing with MS. Just ask the patients.
    We were offered Copaxone until they realised that he had PPMS and it was not worth giving that to him as it would not help him anyway.
    Our life already is one of incredible frustration and pain. I don't see it being improved by the Neurolgy community in the UK. How can they help us? They can't even manage his symptoms,let alone pretend to treat him.
    I really think someone will discover a cure accidentally whilst researching something else.
    I hope this happens soon, I really don't want others to go though what we are going through.

    ReplyDelete
    Replies
    1. Maybe you should have given Copaxone a try since it did show a statistically significant reduction in progression in the male population:

      http://www.ncbi.nlm.nih.gov/pubmed/19426995

      Given this and the mountain of data that shows it has neuropotective effects, this should have been a no brainer. I guess this is why the husband of the vice president of the CSSVI Alliance takes this drug (but only attributes his success to the CSSVI treatment of course).

      You can't tell anything about a drugs effect from short progressive trials that were conducted in the past. If they retested this drug with new endpoints which they will use for new candidate PPMS drugs, I'm sure the results would be different.

      Failure to tolerate daily injections does not equate to a failure of a drugs efficacy.

      Delete
  4. I was one of the first patients to go to Stanford University Hospital to have bilateral jugular stents and I experienced a significant improvement in bladder function and night spasms but nothing else. This gradually diminished over the months and years following this 2009 treatment. I then underwent further angioplasty in 2012 and I immediately suffered a significant relapse within hours of the treatment.
    I'd say altering blood flow had a significant but not necessarily good impact on my MS.

    ReplyDelete
  5. So what kind of veins problems did they find? How did they treated them? Any reference about this in the full text?
    Of course not. "Venous angioplasty" in CCSVI related veins is like pushing a button: Any Interventionalist can do it, no experience necessary.

    But, since improper handling of the veins makes MS worse, this is proof that vein pathology is causal to MS. Too simple for you to swallow, ah?

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  6. Any idea why evaluating CCSVI on the basis of CDMS can never give consistent and conclusive results :-)) ?

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  7. What about the first, in fact the only telltale CCSVI criterion? There are institutions appearing predestined to evaluating it - but none of them seems to have given it a try! No wonder, there is a risk of rendering both angioplasties as well as MS medications superflous:

    ReplyDelete
    Replies
    1. Dear Dr Schelling
      thank you for writing to Dr Bourdette et al - given the lack of specificity of CDMS perhaps they will see the irony of wishing for the end of vascular studies in MS when the only disease specific thing that can be shown about MS is its vein (not venule!) dependent lesion spread.
      http://www.ccsvi-sm.org/node/2022

      Delete
    2. "In order to achieve predictable cures....the conditions and events underlying its venous pathology have to be understood."

      Some have argued first you have to show the problem actually exists

      Delete
  8. MouseDoctor, who can ask or deny that the problem of the venous flow reversals into brain and spinal canal exists ... having grasped the message of www.ms-info.net and taken its findings seriously???.

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  9. We do not normally allow advertisements on the blog. We can see that the link provided forwards to a work by Dr. F. Alfons Schelling-The bible of VV.

    Perhaps it is time that this work is updated. As can be noted that very little of the source information is in the twenty second or even the twenty first century. Much has been published since.

    The work needs to be written in a digestible format
    Is this work properly peer reviewed to ensure that the facts are correct?

    Does the conflict of interests/author information section need updating?

    "As to ask or deny"...I suspect there are a number of pathologists may take up the case.
    Please search through the comments years ago...about this work if interested

    ReplyDelete

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