Thread: ChinaSCINet Update

  1. #1371
    Quote Originally Posted by paolocipolla View Post

    I wonder why Wise doesn't seem to consider any scaffold for future clinical trials in ChinaSCINet

    Paolo
    Do researchers implant a biodegradable scaffold every time they inject a paralyzed rat with stem cells and it starts walking again?

    If the researchers inject a paralyzed rat with stem cells and leave the scaffold out, does the rat fail to walk again?

    Perhaps there isn't enough preclinical safety/efficacy data available yet to justify bringing scaffolds to human trial when there are other therapies showing more promise?

    Perhaps evidence suggests a scaffold isn't necessary?
    Last edited by crabbyshark; 12-13-2012 at 12:09 AM.

  2. #1372
    Quote Originally Posted by crabbyshark View Post
    Do researchers implant a biodegradable scaffold every time they inject a paralyzed rat with stem cells and it starts walking again?

    If the researchers inject a paralyzed rat with stem cells and leave the scaffold out, does the rat fail to walk again?

    Perhaps there isn't enough preclinical safety/efficacy data available yet to justify bringing scaffolds to human trial when there are other therapies showing more promise?

    Perhaps evidence suggests a scaffold isn't necessary?
    Which evidece?

    Scaffolds could be usefull in many ways to repair the spinal cord. As far as I know at this stage of research I see it difficult to say for sure if they will be needed or if they will not be needed.
    If you know that for sure, it would be good if you could provide real convincing evidence to support what you say.

    Paolo
    Last edited by paolocipolla; 12-13-2012 at 01:31 PM.
    In God we trust; all others bring data. - Edwards Deming

  3. #1373
    Quote Originally Posted by paolocipolla View Post
    I wonder why Wise doesn't seem to consider any scaffold for future clinical trials in ChinaSCINet

    Paolo
    Here we go again... let's find some little thing to pick at and then make Wise waste his precious time responding to your continued aggression.

    I'm sure Wise and his colleagues are analyzing all treatment possibilities and moving forward on the ones that show the greatest potential.
    I am the Quad in Quadomated. Come read about Life and Technology through the Eyes of a Quad
    http://www.Quadomated.com/

  4. #1374
    Quote Originally Posted by paolocipolla View Post
    Which evidece?

    Scaffolds could be usefull in many ways to repair the spinal cord. As far as I know at this stage of research I see it difficult to say for sure if they will be needed or if they will not be needed.
    If you know that for sure, it would be good if you could provide real convincing evidence to support what you say.

    Paolo
    Scaffolds could be useful, but scaffolds could also not be useful. If axons are growing across the injury site without scaffolds, that might indicate scaffolds may not be as useful, and that other therapies would be more useful.

    I believe Dr. Wise saying his "data suggests that many axons are growing across the injury" is convincing evidence. I believe him when he says some people are beginning to walk again, too.

    Paolo, if you are so confident that axons are not growing across the injury site, or that people from the Kunming study are not beginning to walk again, would you like to place a wager on it and take advantage of my naivety?

    We could transfer the funds via PayPal. $100? $200? Even odds?

    I am very serious about this.

  5. #1375
    I have moved some posts that were off topic. This topic should be about ChinaSCINet and the trials that it is conducting. Thank you. Wise.

  6. #1376
    Quote Originally Posted by havok View Post
    Idk if this is the wrong place to ask this, but I recent found out the my t10 burst fracture was more than a contusion. Appearently the bone exploded inwards into the spinal cord(maybe severing it idk how bad). And from what I understand these trials are only for contusion. Is there any way to fix both contusion and penetration injuries or is it a lost cause?
    havok,

    Our current trials do not rule out penetrating injuries of the spinal cord. We do leave it to the discretion of surgeons to exclude patients whom they think may present difficulties to expose or to transplant. This include lesions that exceed 2 vertebral segments in length and transected spinal cords.

    Wise.

  7. #1377
    Quote Originally Posted by paolocipolla View Post

    Thank you Wise,

    I hope that when you will publish the data you will make available also videos of the people "walking".

    Paolo
    Paolo,

    This decision will be up to the investigators. My own feeling is that showing selected videos of a study often have undue influence on public perception of trial results. If one chooses to show videos of the best walkers in a study, this will create a perception (no matter how many caveats are given) that all the patients will recover to this extent. There is no easy way to choose a video of an "average" walker in the study. So, if one video is shown, videos of all the patients should be shown but this is often impractical and the temptation is for authors to make the results of the study more impressive. However, if the videos clarify what is meant by "walking", I do favor showing videos. So, whether I would support such videos will depend on the videos that the investigators want to present.

    Wise.
    Last edited by Wise Young; 12-15-2012 at 11:20 PM.

  8. #1378
    [QUOTE=corinne4cure;1624831]
    Quote Originally Posted by Wise Young View Post

    Dear Wise,
    One more question: if I understood correctly, there was a comparison between people who got the treatment only, and some other group who received both the treatment + locomotor training in Kunming.
    What about comparing people who had treatment only to people who received locomotor training only? has this been done ?

    If I remember well, you have always been quite positive about the intensive locomotor training given in Kunming. What I am trying to figure out through this question is whether the treatment has (so far) influenced the ambulation capabilities of patients in combination with locomotor training, or whether that progress was only or mainly due to intensive locomotor training itself.

    I understand it is too early for any conclusion and further functional progress might still happen should the white matter growth lead to actual new connections and regained motor control, but I am just trying to understand the current results better.

    thanks a lot in advance for your explanations. Corinne
    Corinne,

    Let me first say that we are doing phase II trials. People are expecting too much of these trials. These are not intended to prove or disprove efficacy. Rather, they are intended to provide information concerning the best and safe dose, route of treatment, and hopefully indicate some trend towards efficacy. Pivotal trials (Phase III) will be the trials that will resolve questions such as the one that you ask. The question and problem is how we can do this in a convincing way. Let me explain.

    Our phase III trials will be evaluating three therapies: umbilical cord blood mononuclear cells, lithium, and intensive locomotor training. All three may have strong placebo effects. To rule out placebo effects, the trial should be double-blinded, i.e. neither the subjects nor the evaluators know what therapies the subjects have received. Unfortunately, two of the therapies are difficult to blind. Both the subjects and evaluating doctors can easily tell whether the subjects have had surgery or are undergoing intensive locomotor training. So double blinding will be difficult, if not impossible.

    If we don't do a double-blinded study, critics will say that surgery alone or locomotor training alone can make people walk. By the way, these are often the same critics who claim that no therapy can restore function to "complete" chronic spinal cord injury but consistency is not a hobgloblin of critics. Millions of patients have had surgery in the chronic stage of after complete ASIA A spinal cord injury and very few have recovered substantial locomotor function after surgery. So, even though surgery alone is very unlikely to restore function, the clinical trial must somehow prove that it does not.

    Likewise, there is little evidence that people who have chronic "complete" (ASIA A) spinal cord injury will recover walking after intensive locomotor training. Yes, some people such as Patrick Rummerfield recover walking years after severe spinal cord injury and is running marathons. To my knowledge, he has not received experimental regenerative therapies other than exercise. However, while not quite as rare as hen's teeth, people like Pat are rare. Suzy Harkema and many investigators have been studying treadmill locomotor training of people with chronic ASIA A injuries. They find that training seldom results in people achieving unassisted locomotion. My own observations of the Kunming locomotor training program suggests that intensive 6:6:6 overground locomotor training is not sufficient for locomotor recovery in people with chronic "complete" (ASIA A) spinal cord injury.

    What is our solution to this problem in ChinaSCINet? Because we really cannot blind subjects to the placebo effects of intensive 6:6:6 locomotor program, we decided to encompass the placebo and the physical effects in the ChinaSCINet. After all, who cares if the mechanism is placebo or physical as long as it works. In the ChinaSCINet trial, we are planning to randomize a subpopulation of subjects and send them to Kunming for locomotor training. In the other centers, we plan to monitor the number of hours that the subjects engage in locomotor training (using pedometers and daily diaries). This will tell us whether or not locomotor training restores function in people and the intensity of training that is necessary.

    In the U.S., we are planning a phase II trial to compare subjects that are randomized to 6:6:6 (i.e. 6 hours a day, 6 days a week, for 6 months) to 3:3:3 (i.e. 3 hours a day, 3 days a week, for 3 months) training programs. This is supposed to establish feasibility. Each participating center will have a rehabilitation only group, consisting of 3:3:3 training and encouragement for the subjects to "walk to tolerance" in the remaining time. In the phase III trials, we plan to compare rehab only, UCBMC transplant only, lithium only, and UCBMC+lithium. I am worried that if we don't have a intensive locomotor training program in the U.S., we will not see any locomotor recovery.

    Wise.

  9. #1379
    [QUOTE=Wise Young;1626637]
    Quote Originally Posted by corinne4cure View Post

    Corinne,

    Let me first say that we are doing phase II trials. People are expecting too much of these trials. These are not intended to prove or disprove efficacy. Rather, they are intended to provide information concerning the best and safe dose, route of treatment, and hopefully indicate some trend towards efficacy. Pivotal trials (Phase III) will be the trials that will resolve questions such as the one that you ask. The question and problem is how we can do this in a convincing way. Let me explain.

    Our phase III trials will be evaluating three therapies: umbilical cord blood mononuclear cells, lithium, and intensive locomotor training. All three may have strong placebo effects. To rule out placebo effects, the trial should be double-blinded, i.e. neither the subjects nor the evaluators know what therapies the subjects have received. Unfortunately, two of the therapies are difficult to blind. Both the subjects and evaluating doctors can easily tell whether the subjects have had surgery or are undergoing intensive locomotor training. So double blinding will be difficult, if not impossible.

    If we don't do a double-blinded study, critics will say that surgery alone or locomotor training alone can make people walk. By the way, these are often the same critics who claim that no therapy can restore function to "complete" chronic spinal cord injury but consistency is not a hobgloblin of critics. Millions of patients have had surgery in the chronic stage of after complete ASIA A spinal cord injury and very few have recovered substantial locomotor function after surgery. So, even though surgery alone is very unlikely to restore function, the clinical trial must somehow prove that it does not.

    Likewise, there is little evidence that people who have chronic "complete" (ASIA A) spinal cord injury will recover walking after intensive locomotor training. Yes, some people such as Patrick Rummerfield recover walking years after severe spinal cord injury and is running marathons. To my knowledge, he has not received experimental regenerative therapies other than exercise. However, while not quite as rare as hen's teeth, people like Pat are rare. Suzy Harkema and many investigators have been studying treadmill locomotor training of people with chronic ASIA A injuries. They find that training seldom results in people achieving unassisted locomotion. My own observations of the Kunming locomotor training program suggests that intensive 6:6:6 overground locomotor training is not sufficient for locomotor recovery in people with chronic "complete" (ASIA A) spinal cord injury.

    What is our solution to this problem in ChinaSCINet? Because we really cannot blind subjects to the placebo effects of intensive 6:6:6 locomotor program, we decided to encompass the placebo and the physical effects in the ChinaSCINet. After all, who cares if the mechanism is placebo or physical as long as it works. In the ChinaSCINet trial, we are planning to randomize a subpopulation of subjects and send them to Kunming for locomotor training. In the other centers, we plan to monitor the number of hours that the subjects engage in locomotor training (using pedometers and daily diaries). This will tell us whether or not locomotor training restores function in people and the intensity of training that is necessary.

    In the U.S., we are planning a phase II trial to compare subjects that are randomized to 6:6:6 (i.e. 6 hours a day, 6 days a week, for 6 months) to 3:3:3 (i.e. 3 hours a day, 3 days a week, for 3 months) training programs. This is supposed to establish feasibility. Each participating center will have a rehabilitation only group, consisting of 3:3:3 training and encouragement for the subjects to "walk to tolerance" in the remaining time. In the phase III trials, we plan to compare rehab only, UCBMC transplant only, lithium only, and UCBMC+lithium. I am worried that if we don't have a intensive locomotor training program in the U.S., we will not see any locomotor recovery.

    Wise.
    Wise, I can only assume that double blind/blind trials are being utilized over simple mathematical significance because of the limited number of patients available to test. Is this correct? Presumably a higher 'n' would give clearer and more convincing results but pragmatics (time/money/availability of subjects) prevent this from happening?

  10. #1380
    Senior Member
    Join Date
    Jun 2005
    Location
    Norway
    Posts
    17,427
    Cripwalk. It’s not so much about pragmatics. Randomized, double blind, placebo-controlled clinical trials are the gold standard.

Similar Threads

  1. ChinaSCINET Update
    By Schmeky in forum Cure
    Replies: 11
    Last Post: 06-16-2008, 06:25 PM
  2. ChinaSCINET on Schedule?
    By Schmeky in forum Cure
    Replies: 11
    Last Post: 01-27-2008, 05:53 AM
  3. Dr. Young and ChinaSciNet
    By Imight in forum Cure
    Replies: 17
    Last Post: 01-14-2008, 12:51 AM
  4. ChinaSCINET Schedule
    By Schmeky in forum Cure
    Replies: 4
    Last Post: 07-11-2007, 04:30 AM
  5. ChinaSCINET, On Schedule?
    By Schmeky in forum Cure
    Replies: 56
    Last Post: 01-30-2007, 03:46 PM

Posting Permissions

  • You may not post new threads
  • You may not post replies
  • You may not post attachments
  • You may not edit your posts
  •