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    Originally posted by jsilver View Post
    Thanks Wise.

    Dear CC community,

    We are all in this together and until we help those with SCI get better we will not rest. Good heated scientific debate stirs passion and helps maintain our focus on what is really important...to develop real solutions to cure chronic spinal cord injury. I stirred the pot yet again. Ch'ase has, indeed, been shown to be effective after a contusive type of injury. Importantly, we will report shortly the development of a second generation and markedly improved strategy that works better than ch'ase to overcome CSPG mediated inhibition. The new therapy is highly effective in restoring function (locomotion and bladder function) after severe contusive injury using a simple, systemic route of administration. This time around we don't need Acorda and we have a much easier road to clinical trials. I still think I have a few good ideas left in this old brain and I have and will continue to dedicate most of what I think about to the SCI community.
    Thank you, sincerely. Some of the comments here must make you wonder if it's even worth it.

    Comment


      thank you IMHopeful

      We are going to w2w this year, I can't wait
      Last edited by lunasicc42; 24 Jun 2012, 5:01 PM.
      "That's not smog! It's SMUG!! " - randy marsh, southpark

      "what???? , you don't 'all' wear a poop sac?.... DAMNIT BONNIE, YOU LIED TO ME ABOUT THE POOP SAC!!!! "


      2010 SCINet Clinical Trial Support Squad Member
      Please join me and donate a dollar a day at http://justadollarplease.org and copy and paste this message to the bottom of your signature

      Comment


        Dr Wise Young,

        Thank you for your dedication in finding a cure for spinal cord injuries! I am a complete c5-c6 quad from a gun shot wound. Are any of your trials involving similar cases like mine? If so, where? If not, would you consider me as a candidate for stem cell therapy after the trial phases are completed, or, at anytime?

        Keep up the great work!

        Comment


          Originally posted by Littlerosey36 View Post
          Dr Wise Young,

          Thank you for your dedication in finding a cure for spinal cord injuries! I am a complete c5-c6 quad from a gun shot wound. Are any of your trials involving similar cases like mine? If so, where? If not, would you consider me as a candidate for stem cell therapy after the trial phases are completed, or, at anytime?

          Keep up the great work!
          Littlerosey,

          One of the subjects in our Hong Kong trial had spinal cord injury from gunshot. Therefore, we have not been excluding such patients from our trials to date. I don't know whether we will or not in the phase 3 trial because that depends on the decision of the investigators. However, so far, we have not.

          Wise.

          Comment


            I removed some posts to the Members Only Forum /forum/showthread.php?p=1547468#post1547468.

            Wise.

            Comment


              Originally posted by Wise Young View Post
              Littlerosey,

              One of the subjects in our Hong Kong trial had spinal cord injury from gunshot. Therefore, we have not been excluding such patients from our trials to date. I don't know whether we will or not in the phase 3 trial because that depends on the decision of the investigators. However, so far, we have not.

              Wise.
              Sweet, I'am glad to hear that
              keep (rolling) Walking

              Please join me and donate a dollar a day at http://justadollarplease.org and copy and paste this message to the bottom of your signature

              Comment


                Originally posted by Wise Young View Post
                Paolo,

                Let us examine each of the assumptions behind your far reaching conclusion that networks are not necessary:

                1. You seem to be assuming that recruitment of chronic spinal cord injury patients is easy. Let me assure you that it is not. Despite substantial effort and a great deal of publicity for two years, Hong Kong University and the Chinese University of Hong Kong were not able to find more than 8 chronic ASIA A patients that had neurological levels between C5 and T11. Even in Kunming, where they operate on over 400 acute spinal cord injury cases per year and where there is no dearth of acute or chronic patients, it took over 6 months to recruit and transplant 20 chronic SCI subjects. There are many reasons why individual patients may not fulfill inclusion and exclusion criteria, are not ready or available for the trials, or are not willing to take the risk, etc. I believe that we probably should not expect any individual center anywhere in the world except China to treat and assess more than 20 patients per year.

                2. The numbers of patients required for phase 3 trials are larger than you are assuming for the following reasons. First, you must have controls and multiple treatment groups. In the U.S., we will need to compare all components of a treatment against a combination before you can conclude that the combination is effective. In the case of UCBMC and lithium, this means that you need to have four treatment groups: rehabilitation only, rehabilition + lithium, rehabilitation + UCBMC, and rehabilitation + UCBMC + lithium. If you need 50 subjects per treatment group, that will require 200 subjects. Second, we must consider injury variables. So far, we are talking about only ASIA A subjects. Perhaps the treatment would work in ASIA B and C. Just including these two groups would triple the number of subjects. Third, we must consider treatment variables. For example, if we want to assess whether intensive locomotor training is necessary (the rehab alone group answers the question of sufficiency but not necessity), we would have to have UCBMC+lithium with and without locomotor training. If we want to know whether HLA-matching is necessary, i.e. compare HLA 4:6, 5:6, and 6:6 matches, a trial of 400 subjects would be required. Only a network can do trials of over 100 subjects.

                3. You are assuming that chronic spinal cord injury subjects will travel and return for followup exams and therefore clinical trial centers can be located anywhere. It is a good idea and I have in fact looked into this possibility of setting up a center in one place where many people would go. I grant you that many patients may be willing to travel. If it were only the surgery, it might even be possible to do a trial where the subjects come back for followup examinations. In my experience, however, many people do not keep their promises. There are many reasons why people do not come back, not the least of which is that it is expensive and time-consuming for somebody to travel long distances for examinations. Particularly if they do not think the treatment is working, they don't come back. Each subject represents investments of over $100,000 to treat in a clinical trial and if they do not come back for followup, that investment is lost. The requirement for intensive and prolonged rehabilitation may further restrict the number of subjects. Our preliminary data suggest that if you don't engage in intensive walking training, locomotor recovery will be limited. This factor alone is likely to severely limit clinical trial tourism. Will everybody who travels to join a clinical trial be ready to give up 3 months of their lives and to return again at 6 months and a year (or more) after the treatment? Some might but I suspect that many would not be able to do it.

                4. You assume that the results of a single trial center would be credible to the rest of the world. I can assure you that this is not the case. I know of many groups that have done 20-50 subject trials and showed very promising results and then cannot get their results published in the best journals. The reviewers turn down the papers and say that they don't believe. The reviewers are tantamount to saying that the investigators are lying. To be credible, particularly in controversial or first-in-human therapeutic successes, you must have multicenter phase 3 trials to convince the rest of the world that the treatment is efficaceous.

                Finally, you cite Schwab and Buchli who are calling for more phase 1 and 2 proof-of-concept trials. I agree that we should have more phase 1 and 2 trials, but not at the expense of not doing phase 3 trials. Phase 3 trials are essential for proving efficacy and obtaining regulatory approval. Phase 1 and 2 trials are pre-coital, if you know what I mean. If we want therapies to be approved by the regulatory authorities, they must pass through phase 3 trials. We must do phase 3 trials if the treatments are to help people. Let me give you an example from the sports world. It would be like preparing a racing car to win all the time trials and get a good pole position but not having the funds to take the car to the final race. The phase 3 trial is not only the final race, it is the only race that counts. Multicenter trials are essential for phase 3 and networks are essential for efficient multicenter trials.

                Wise.
                Wise,

                I'll try to be more clear on sevral points.

                1) I didn't say that recruitment of chronic spinal cord injury patients is easy.
                I agree it is still a lot of work, but think it is much easier than with acute SCI as you have an existing population with chronic SCI that can travel etc..
                About the Hong Kong trial you had been able to recuit just 8 patients in two years because you couldn't accept patients non Hong Kong resident.

                I think it was a mistake to run a trial in a place where you can't accept patients from other countries.

                Many CC members are willing to parteciapate to your trial and willing to come back for examinations when needed, but they can't because you can't accept patients from around the world.
                I think it is quite clear that to accelate SCI clinical trial for chronic SCI at this stage it very important to have a center that can accept candidates from around the world.

                2) I have 2 questions here:

                How many patients per arm would you need in a phase III ACUTE SCI
                trial?
                How many patients per arm would you need in a phase III CHRONIC SCI trial?

                3) You say:
                "Will everybody who travels to join a clinical trial be ready to give up 3 months of their lives and to return again at 6 months and a year (or more) after the treatment? Some might but I suspect that many would not be able to do it."

                Ask for a deposit to the partecipants before they join the trial.

                4) You say:
                "You assume that the results of a single trial center would be credible to the rest of the world."

                Well if you have enrolled patients with Thoracic SCI, with no function below the level of injury and now some of them are walking I belive it shoud NOT be difficult to convivnce doctors the the therapy is working.
                I also assume you can show medical examinations (done by indipendent examiners) of the patients before and after the treatment with the motor scores etc., or the medical community will considere your claims at the level of the ones of Geeta Shroff end others (NO COMPARISON INTENDED HERE).

                Finally I want phase III trial of therapies that can restore significant functions, not something that has the same efficacy of pacebo even less,
                That is the pharma business and I am not intersted in that.

                Paolo
                Last edited by paolocipolla; 27 Jun 2012, 6:51 PM.
                In God we trust; all others bring data. - Edwards Deming

                Comment


                  Originally posted by paolocipolla View Post
                  Finally I want phase III trial of therapies that can restore significant functions, not something that has the same efficacy of pacebo even less,
                  That is the pharma business and I am not intersted in that.

                  Paolo
                  Then why don't you start such a clinical trial?

                  Comment


                    Originally posted by paolocipolla View Post
                    Wise,

                    I'l try to be more clear on sevral points.

                    1) I didn't say that recruitment of chronic spinal cord injury patients is easy.
                    I agree it is still a lot of work, but think it is much easier than with acute SCI as you have an existing population with chronic SCI that can travel etc..
                    About the Hong Kong trial you had been able to recuit just 8 patients in two years because you couldn't accept patients non Hong Kong resident.

                    I think it was a mistake to run a trial in a place wher you can't accep patients from other countries.

                    Many CC members are willing to parteciapate to your trial and willing to come back for examinations when needed, but they can't because you can't accept patients from around the world.
                    I think it is quite clear that to accelate SCI clinical trial for chronic SCI at this stage it very important to have a center that can accept candidates from around the world.

                    2) I have 2 questions here:

                    How many patients per arm would you need in a phase III ACUTE SCI
                    trial?
                    How many patients per arm would you need in a phase III CHRONIC SCI trial?

                    3) You say:
                    "Will everybody who travels to join a clinical trial be ready to give up 3 months of their lives and to return again at 6 months and a year (or more) after the treatment? Some might but I suspect that many would not be able to do it."

                    Ask for a deposit to the partecipants before they join the trial.

                    4) You say:
                    "You assume that the results of a single trial center would be credible to the rest of the world."

                    Well if you have enrolled patients with Thoracic SCI, with no function below the level of injury and now some of them are walking I belive it shoud NOT be difficult to convivnce doctors the the therapy is working.
                    I also assume you can show medical examinations (done by indipendent examiners) of the patients before and after the treatment with the motor scores etc., or the medical community will considere your claims at the level of the ones of Geeta Shroff end others (NO COMPARISON INTENDED HERE).

                    Finally I want phase III trial of therapies that can restore significant functions, not something that has the same efficacy of pacebo even less,
                    That is the pharma business and I am not intersted in that.

                    Paolo
                    1.hongkong trial is fund by Hongkongnese,one condition is Hongkong residents only.Well,by the way,Beijing has stem cell center welcomes other country patients.if u want to go,I can send information to u.
                    3.It is not allowed to take deposit for join a clinic trial.
                    4.Well,again,Beijing Wujing hospital had been claimed cured sci for a few years,but the data only in that hospital.

                    Comment


                      Y8, IF cure has been claimed in china, I woul dthink that this would be broadcast over the world and made available all over the world. the walking that Paolo mentioned has to be defined. Is it acutes or chronics. Is it something never seen before or is a result of wise's treatment.
                      I understnad the Hong Kong thing. I also see the differnce incost between china, Switzerland, and the USA. this is one of the beifits that will be accrued with Obama;s Affordabel Health . wise has been reluctant to tell what has been achieved except safety. Dr Silver has a therpay he might try, years away from clinical trial, and disagrees with wise's ideas and findings. the board only want s a successful trial that will be available ot us in the near future.

                      anthony

                      Comment


                        My specific comments are embedded and my general comments follow.

                        Originally posted by paolocipolla View Post
                        Wise,

                        I'l try to be more clear on sevral points.

                        1) I didn't say that recruitment of chronic spinal cord injury patients is easy.
                        I agree it is still a lot of work, but think it is much easier than with acute SCI as you have an existing population with chronic SCI that can travel etc..
                        About the Hong Kong trial you had been able to recuit just 8 patients in two years because you couldn't accept patients non Hong Kong resident.
                        @ I agree.

                        I think it was a mistake to run a trial in a place wher you can't accep patients from other countries. Many CC members are willing to parteciapate to your trial and willing to come back for examinations when needed, but they can't because you can't accept patients from around the world. I think it is quite clear that to accelate SCI clinical trial for chronic SCI at this stage it very important to have a center that can accept candidates from around the world.
                        @ Why would the Hong Kong government pay for treatments of patients from other countries? You have the cart before the horse. If we had a billion dollars to do the trial, perhaps we can do something like that what you suggest. Otherwise, we have to follow where opportunity leads us and circumstances restrict us to do.


                        2) I have 2 questions here:
                        How many patients per arm would you need in a phase III ACUTE SCI
                        trial?
                        How many patients per arm would you need in a phase III CHRONIC SCI trial?
                        This is of course what phase 2 trials are intended to find out. We would need to estimate the variability (i.e. standard error of mean) of treated and control populations and then do a power analysis to find out how many subjects are needed to detect X percent change in the outcome measure. We know from the methylprednisolone trial that about 60 subjects per treatment arm were necessary to detect 10% differences in motor and sensory score changes. We don't yet have that data from our phase 2 trials. I am hoping that that number will be lower for chronic ASIA A subjects.


                        3) You say:
                        "Will everybody who travels to join a clinical trial be ready to give up 3 months of their lives and to return again at 6 months and a year (or more) after the treatment? Some might but I suspect that many would not be able to do it."
                        Ask for a deposit to the partecipants before they join the trial.
                        Interesting idea. I am not sure that institutional review boards would approve such a proposal. They would approve, however, a payment incentive, i.e. pay subjects to come back. Again, this is a question of funding and not a question of possibility.

                        4) You say:
                        "You assume that the results of a single trial center would be credible to the rest of the world."

                        Well if you have enrolled patients with Thoracic SCI, with no function below the level of injury and now some of them are walking I belive it shoud NOT be difficult to convivnce doctors the the therapy is working.

                        @ The Kunming group did a study showing that approximately 50% of 30 subjects with ASIA A recovered ability to walk unassisted when they were treated with intradural decompression. The study did not do a control. Over half of the subjects had ASIA A thoracic spinal cord injuries. The study was turned down by the two major neurosurgery journals. The reviewers said that they did not believe the results, which is tantamount to saying that they thought we were lying.

                        Even when the results were published by a multicenter study from the United States, doctors may not believe. Take a look at the National Acute Spinal Cord Injury Study (NASCIS II), where we did a double-blind randomized placebo-controlled trial involving 487 subjects published in the New England Journal of Medicine (the most prestigious medical journal in the world). During the two years that followed publication of that study in 1990, less than a third of patients with acute spinal cord injury in the United States received the high-dose methylprednisolone (MP) therapy. It took several years of concerted effort to increase the usage rate of MP to 90% by the mid-1990's. But, once that effort slackens, doctors stop using the drug, even though there has been no new information from clinical trials indicating that the drug is ineffective or unsafe. Today, less than 50% of spinal cord injured patients in the United States and Europe are receiving MP. In 1991, the investigators of NASCIS decided that the data was too strong to allow us to conduct a second placebo-controlled trial of MP. The FDA requires two phase 2 randomized controlled trial for approval of a therapy. In some ways, I wish that we had gone ahead to a second phase III trial and gotten the spinal cord injury approved as an indication for MP. Many thousands of patients would have received the drug and gotten an average of 20% better recovery. But, such a trial would have been impossible to do after the publication of the first trial.

                        Let me give you another example from another field. Jaing, et al. from the Chang Gung Memorial Hospital in Taiwan (one of the best and most respected hospital in Taiwan) published a paper in 2010 reporting that he had 88% survival and disease-free survival in 74% of 35 kids with thalassemia treated with umbilical cord blood from Stemcyte. Thalassemia is a genetic disease that is easily documented. In 2011, Ruggeri, et al. from Italy published a study which reported the European experience using umbilical cord blood from multiple cord blood banks and they found only 67% total survival and 23% disease-free survival in 35 kids of thalassemia. Ruggeri, et al. recommended that umbilical cord blood cells not be used to treat kids of thalassemia except in a clinical trial setting. These kinds of differences happen amongst clinical trials. Many doctors around the world still refuse to use umbilical cord blood to treat thalassemia, even when they cannot find HLA-identical siblings to donate bone marrow, relegating the child to a life-time of blood transfusions every two or three weeks, along with all the expense and complications that such frequent transfusions bring.


                        I also assume you can show medical examinations (done by indipendent examiners) of the patients before and after the treatment with the motor scores etc., or the medical community will considere your claims at the level of the ones of Geeta Shroff end others (NO COMPARISON INTENDED HERE).
                        In our Hong Kong trials, we had OT/PT examiners at each hospital as well as well as third-party examiners at the MacLehose rehabilitation center. In Kunming, we have designated nurse-doctor teams of experienced examiners (who are actually going to the homes of the patients to examine them because many cannot come back to the hospital for the followup exams). Credibility is not easy to achieve.

                        Finally I want phase III trial of therapies that can restore significant functions, not something that has the same efficacy of pacebo even less,
                        That is the pharma business and I am not intersted in that.
                        @ What you want is not always what you get in trials. Of course, all of us would love to see significant functional improvements from a therapy. I don't know where you get the impression (as indicated by your signature quotes) that "pharma business" wants something less. In fact, approval of third party re-imbursement for therapies now require not only significant evidence of improvement but the improvement must be meaningful. So, let me assure that pharmaceutical industry want treatments that produce functionally significant improvement.


                        Paolo

                        Clinical trials have two purposes. The first if of course to show that treatments are safe and effective. The second is to show that the treatments are not safe or are not effective. The latter should not need to be said but people (including most scientists and clinicians) forget this. Right now, many medical tourism clinics around the world are offering umbilical cord blood cell therapy of spinal cord injury, pointing to animal studies that show efficacy. If our trials show that umbilical cord blood mononuclear cells transplanted into the injury site, with or without lithium, do not change neurological function in patients, we can say definitively that the therapy does not work and recommend against its use. On the other hand, if the treatment does work, either with or without lithium, we want to be able to strongly recommend its use and back up that recommendation with global phase III trials.

                        Phase II trials are not sufficiently powered to be statistically convincing. On the other hand, they can show trends and, based on those trends, I believe that it is worthwhile going ahead to phase III trials. You will see the data from the trends as soon as all the data is collected and we submit the data for publication. Usually journals allow scientists and clinicians to share data before publication in symposia but premature publication of the data on internet may harm the chances of the data being accepted for publication in the best possible journal. That is the reason why I cannot present the data here.

                        Wise.
                        Last edited by Wise Young; 28 Jun 2012, 1:09 AM.

                        Comment


                          Dr. Wise,

                          When discussing the different groups in the Open House presentation, you mention that the fifth group, the group receiving UCBMC+MP+Li, were only at their six week stage and implied it was too early to really say anything about their progress. This group would be at about the ten week stage now. Perhaps it is still too early to say, but can you broadly indicate at all how this group is doing?

                          I've been coming to this forum for years and it has been a constant source of encouragement. Thank you so much for all the time and energy you've spent helping people and trying to fix spinal cord injury. It is amazing.
                          Last edited by crabbyshark; 30 Jun 2012, 5:35 PM.

                          Comment


                            Chronic incomplete lower thoracic lumbar

                            Dear Dr Young

                            First of all I wold like to just thank you for all your hard work and dedication to the cause. You are an inspiration and a hero to me. I truly believe that good things are coming in the near future.

                            I am a t12 or L1/L2 incomplete. Ive been told different things b different doctors. I think based of my movement, sensation I'm more likely L1/L2

                            I walk with crutches full time. I have braces for ankle support as I have no strength below my knees, though I do have some sensation.

                            I am now 10 post injury due to a GSW, which they originally said severed the cord.. But they were obviously wrong

                            What are the chances that I would be eligible for your therapy, either in a phase 3 trial or later in the future.

                            Thank you again

                            James Paik

                            Comment


                              Originally posted by keeping on View Post
                              Y8,IF cure has been claimed in china, I woul dthink that this would be broadcast over the world and made available all over the world. the walking that Paolo mentioned has to be defined. Is it acutes or chronics. Is it something never seen before or is a result of wise's treatment.
                              I understnad the Hong Kong thing. I also see the differnce incost between china, Switzerland, and the USA. this is one of the beifits that will be accrued with Obama;s Affordabel Health . wise has been reluctant to tell what has been achieved except safety. Dr Silver has a therpay he might try, years away from clinical trial, and disagrees with wise's ideas and findings. the board only want s a successful trial that will be available ot us in the near future.

                              anthony
                              It reminds me of Howard Cosell's career and commentary.

                              http://spinalcordresearchandadvocacy.wordpress.com/

                              Comment


                                Originally posted by crabbyshark View Post
                                Dr. Wise,

                                When discussing the different groups in the Open House presentation, you mention that the fifth group, the group receiving UMBMC+MP+Li, were only at their six week stage and implied it was too early to really say anything about their progress. This group would be at about the ten week stage now. Perhaps it is still too early to say, but can you broadly indicate at all how this group is doing?

                                I've been coming to this forum for years and it has been a constant source of encouragement. Thank you so much for all the time and energy you've spent helping people and trying to fix spinal cord injury. It is amazing.
                                Crabby, we are waiting for the 6 month followup. They are formally examined at 6 weeks, 6 months, and 12 months. That data will be available in November. Thank you for your comments and it is indeed an exciting time. Wise.

                                Comment

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