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Artificial Pancreas Update (Nov 2014)

Discussion in 'Research' started by joshualevy, Nov 15, 2014.

  1. joshualevy

    joshualevy Approved members

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    This is a quick update on several artificial pancreas (AP) projects. The term "artificial pancreas" refers to using a continuous glucose monitor (CGM) to feed data to a computer, which controls an insulin pump, and in some models, a glucagon pump as well. Artificial pancreas refers to using existing technology in all these areas, but connecting them together so that a person does not need to worry about counting carbs or blood glucose levels. It is all done automatically.


    Medtronic Starts Two Phase-III Trials


    Medtronic is currently the leader in commercial development of an artificial pancreas. They have already released CGM/pump combination that automatically shuts down insulin injection if blood glucose levels go too low for too long. This existing technology is very likely to prevent "dead in bed", and it is the first small step towards an artificial pancreas.


    The next step will be what's called "predictive shutoff". While the existing system will only stop insulin when blood glucose levels have already gone too low for too long, the new system will use knowledge of insulin on board and blood glucose trends to cut off insulin before blood glucose levels drop below acceptable levels. This is a big step forward in terms of keeping people in healthy blood glucose ranges, and it is also a big regulatory step forward. It means that software will be making changes based on the expected (future) situation, not the known (past) situation.



    Medtronic is starting two studies of this feature. An American study will use 84 people at several different sites, while an international study will have 100. The American study specifically says it is phase-III, and I suspect the other one is as well, but it doesn't say that specifically. This would be great news, because a new device needs two phase-III trials before it can be approved for marketing in the United States, and both of these studies hope to finish by December 2014. I view these studies as an attempt to get to market with a "step 2" artificial pancreas device as described in the diagram below.


    The American study has one contact person:
    Julie Sekella (818) 5765171 julie.sekella@medtronic.com


    For all these locations (not all of which have started recruiting, yet):

    • AMCR Institute, Inc. Escondido California
    • Stanford University Department of Pediatric Endocrinology, Palo Alto California (Bruce Buckingham)
    • Barbara Davis Center of Childhood Diabetes, Denver Colorado (Satish Garg)
    • Yale University Diabetes Research Program, New Haven Connecticut
    • Atlanta Diabetes Associates, Atlanta Georgia (Bruce Bode)
    • University of Virgina, Charlottesville Virginia (Stacey Anderson)
    • Rainier Clinical Research, Renton Washington (Ronald Brazg)
    The international study has these two locations:

    Clinical Trial Records:
    http://clinicaltrials.gov/ct2/show/NCT02130284
    http://clinicaltrials.gov/ct2/show/NCT02179281
    News: http://www.marketwatch.com/story/medtronic-begins-pivotal-study-of-first-predictive-low-glucose-management-technology-for-people-with-diabetes-2014-10-14?reflink=MW_news_stmp


    There is a third clinical trial, which is described here: http://clinicaltrials.gov/ct2/show/NCT02160184 and which is expected to enroll 12 people and finish Feb 2015. It's not clear to me if it is testing the same predictive shutoff feature as the other two. It is being run in Spain. Contact: Mercedes Rigla, MD, PhD +34-93-745-8412 mrigla@tauli.cat

    Two of the three studies described here refer to a commercial model number: 640G.


    MD-Logic Update



    MD-Logic refers to another group of researchers working on a different artificial pancreas. This AP is in Step 3 or 4 in the diagram below. They recently published new data. People used their artificial pancreas for 6 weeks (night only) in their regular lives. So they were "out and about". This was a cross over trial, meaning each person spent 6 weeks using the closed loop and six weeks not. Half the group used the closed loop first, and half of them used closed loop second. The results were all very good:

    • Reduced time spent in hypoglycemia
    • Increased the percentage of time spent in the target range of 70–140 mg/dL
    • Time spent in substantial hyperglycemia above 240 mg/dL was reduced by a median of 52.2%
    • Overnight total insulin doses were lower in the closed-loop nights
    • The average daytime glucose levels after closed-loop operation were reduced by a median of 10 mg/dL
    Clinical Trial: http://care.diabetesjournals.org/content/37/11/3025?etoc


    Interview with JDRF's Dr. Kowalski


    This interview has a lot of interesting information about how JDRF and AP research interact:
    https://myglu.org/articles/a-pathwa...creas-an-interview-with-jdrf-s-aaron-kowalski


    It includes the JDRF "AP Step/Generations" diagram, which is how they think an AP will be developed over time. You can read more about these steps here:
    http://jdrf.org/research/treat/artificial-pancreas-project/
    [​IMG]


    New Artificial Pancreas Project


    Another new artificial pancreas project is getting underway at Rensselaer Polytechnic Institute, which you can read about here:
    http://news.rpi.edu/content/2014/10...t-enables-clinical-trials-artificial-pancreas
    http://www.meddeviceonline.com/doc/artificial-pancreas-to-begin-clinical-trials-0001
    they have not started human trials yet, but it sounds like they will, soon.


    Are They Working Together?


    One question I get asked about different groups doing similar research is: are they working together? And usually, I don't know. However, in the case of Artificial Pancreas research, I know that the different groups are working together, because in some cases, there is overlap among the researchers. To give you just two examples:

    • Bruce Buckingham is working on the Medtronic clinical trial, the University of Virginia clinical trials, and the planned Rensselaer clinical trial. Plus algorithms that he worked on were used in the Cambridge AP work.
    • Moshe Phillip is working on both the Medtronic and the MD-Logic clinical trials.
    It's clear that the AP groups are not working "in a vacuum". They are all aware of each others work.


    Direct Comparison (Updated)


    The chart below is a comparison of all AP projects which I know about that are either in clinical trials, or about to start them. Some of these projects are not included in this blog posting, but are described in previous postings: http://cureresearch4type1diabetes.blogspot.com/search/label/Artificial Pancreas


    [TABLE]
    [TR]
    [TD]Group
    [/TD]
    [TD]
    FDA

    Phase
    [/TD]
    [TD]
    JDRF

    Step
    [/TD]
    [TD]
    Average BG

    Estimated A1c
    [/TD]
    [TD]
    Size
    [/TD]
    [TD]
    Adolescents?
    [/TD]
    [TD="align: center"]Duration
    [/TD]
    [TD]
    AP Use
    [/TD]
    [/TR]
    [TR]
    [TD]Boston University
    [/TD]
    [TD]
    II
    [/TD]
    [TD]
    6
    [/TD]
    [TD="align: center"]138
    6.4
    [/TD]
    [TD]
    53
    [/TD]
    [TD="align: center"]Yes
    [/TD]
    [TD="align: center"]5 days
    [/TD]
    [TD]24 Hours/Day
    [/TD]
    [/TR]
    [TR]
    [TD]Cambridge
    [/TD]
    [TD]
    II
    [/TD]
    [TD]
    3
    [/TD]
    [TD]
    146

    6.7
    [/TD]
    [TD]
    17
    [/TD]
    [TD]
    No
    [/TD]
    [TD="align: center"]8 days
    [/TD]
    [TD]24 Hours/Day
    [/TD]
    [/TR]
    [TR]
    [TD]MD-Logic
    [/TD]
    [TD]
    II
    [/TD]
    [TD]
    3
    [/TD]
    [TD]

    [/TD]
    [TD]
    24
    [/TD]
    [TD]
    Yes
    [/TD]
    [TD]
    90 days
    [/TD]
    [TD]
    Night Only
    [/TD]
    [/TR]
    [TR]
    [TD]Virginia
    [/TD]
    [TD]
    II
    [/TD]
    [TD]
    3
    [/TD]
    [TD]
    135?
    [/TD]
    [TD]
    13
    [/TD]
    [TD]
    No
    [/TD]
    [TD]
    2 days
    [/TD]
    [TD]
    24 Hours/Day



    [/TD]
    [/TR]
    [TR]
    [TD]Medtronic
    [/TD]
    [TD]
    III
    [/TD]
    [TD]
    2
    [/TD]
    [TD]
    Just

    Started
    [/TD]
    [TD]
    184
    [/TD]
    [TD]
    Yes
    [/TD]
    [TD]
    2 days
    [/TD]
    [TD]
    24 Hours/Day



    [/TD]
    [/TR]
    [TR]
    [TD]Rensselaer
    [/TD]
    [TD]
    [/TD]
    [TD]
    [/TD]
    [TD]
    Not

    Started
    [/TD]
    [TD]
    [/TD]
    [TD]
    [/TD]
    [TD]
    [/TD]
    [TD]




    [/TD]
    [/TR]
    [/TABLE]




    [FONT=Georgia, Times New Roman, serif]Joshua Levy [/FONT]
    http://cureresearch4type1diabetes.blogspot.com
    publicjoshualevy at gmail dot com
    All the views expressed here are those of Joshua Levy, and nothing here is official JDRF or JDCA news, views, policies or opinions. My daughter has type-1 diabetes and participates in clinical trials, which might be discussed here. My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog.
     
  2. MLT2014

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  3. joshualevy

    joshualevy Approved members

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    Two comments:

    First, it really doesn't matter. If the artificial pancreas is ready in 2 years, that will be a great treatment, but if it is ready in 3 or 4 or 5 years, it will still be a great treatment. In my mind, it is really not worthwhile to spend time discussing exactly when it will be available. When it is available, then we will have it. Discussing now, when that will be, is pointless.

    Second, and to answer your question, I think the person quoted in that story is way too optimistic. Although it depends exactly what he means by "artificial pancreas". As I stated above, Metronic already has a "step 1" device available now. I do think they will have a "step 2" device in the market in less than 2 years. (My best guess; gut feeling; no guarantees!) But most people will not consider a "step 2" device to be an artificial pancreas. The device most people consider an AP would be a "step 3" or "step 4" device. In general, I think that all the "research projects" (ie. Bionic Pancreas, MD-Logic, The Cambridge Device, the Univ. of Virgina Device, and the Rensselaer Device), those are all more than a few years out. (My best guess; gut feeling; no guarantees!) In any case, the dates given in that news report are much more optimistic than I feel are likely.

    But really, there is nothing to be gained by speculation about when an AP will be available. When you can buy it; then it is available.

    Joshua Levy
     
  4. MLT2014

    MLT2014 Approved members

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    Have you got a chance to see the "Juvenile Diabetes Cure Alliance's State of the Cure 2014 report?" It appears that there are 4 new projects that could cure Type 1 diabetes (entering human clinical trials): VC-01, Tolerion TOL-3021, Bionic Pancreas, and Cyclosporine Lansoprazole. Our daughter was diagnosed with diabetes within the last three months so we are still learning. We have heard of VC-01 and Bionic Pancreas, but not the others. Any thoughts/comments on Tolerion TOL-3021 and Cyclosporine/Lansoprazole? Thank you
     
  5. MLT2014

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    According to Juvenile Diabetes Cure Alliance State of the Cure 2014 report, 4 new projects that could cure T1D: VC-01, Bionic Pancreas, Tolerion TOL-3021, and Cyclosporine/Lansoprazole. I have heard of VC-01 and Bionic Pancreas, but not familiar with the others. Any comments/thoughts on Tolerion TOL-3021 and Cyclosporine/Lansoprazole? Our daughter recently was diagnosed with diabetes so we are learning. Thank you for taking the time to look into this matter.
     
  6. sszyszkiewicz

    sszyszkiewicz Approved members

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    About a year ago I was in the hospital with my son (newly diagnosed) wondering about cures, reading literally hundreds of web pages about this research or that research, what was possible and what wasnt, timelines, etc...

    Then i came across Joshua's blog and it put things into honest perspective.

    This one post is a good place to start
    http://cureresearch4type1diabetes.blogspot.com/2008/06/understanding-research-funnel.html

    Basically its going to be a while, but its not like the pipeline is empty. There are lots of reasons to be hopeful.

    You will find lots of information about the studies you asked about at Joshuas blog.

    He also did a presentation recently which gives a really good summary of what is going on in the various trials today

    https://m.youtube.com/watch?v=h8Dz9uWj39M
     
  7. swellman

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    Joshua, do I understand your post correctly in that Boston University has 53 people in a Phase II trial on a Fully Automated Multi Hormone Closed Loop device?
     
  8. joshualevy

    joshualevy Approved members

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    That trial is completed and reported on, so it is not on-going at this time. It included 32 adolescents and 20 adults for a total of 53 people. Abstract is here:
    http://www.nejm.org/doi/full/10.1056/NEJMoa1314474#t=articleTop

    MLT2014: as sszyszkiewicz says, I've blogged on all of those cures (except Cyclosporine/Lansoprazole) on my blog:
    http://cureresearch4type1diabetes.blogspot.com/
    If you look on the right side of the blog, you will see a section called "MY MOST IMPORTANT POSTS". It includes the "Funnel" posting that sszyszkiewicz mentioned, but also some others that you might find useful.

    I have not blogged on Cyclosporine/Lansoprazole because I generally blog on research that is in clinical trials (human testing), and I'm not sure that combination is in clinical trials quite yet. The FDA clinical trial record says no, but the company's web site kind of implies that it is. When get confirmation it has started a trial, I'll blog on it.

    Joshua Levy
     
  9. MLT2014

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    Joshua: According to the State of the Cure 2014 report, it appears that the trial size about 130 people for the oral Cyclosporine/Lansoprazole drug combo. Also, eligible age range to participate is 8 - 30 years old. I may have my child participates (if eligible) with more info. I look forward to your blog/update. Many thanks

    SSZYSZKIEWICZ: Thank you.
     
  10. Deal

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    Joshua, this study appears to indicate an ongoing phase 3 trial for Oral Cyclosporine and Oral Lansoprazole

    http://clinicaltrials.gov/show/NCT01762657

    The last line says the record was processed yesterday.
     
  11. joshualevy

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    It depends what you mean by "ongoing". If you look at the top of the page, it says this:
    This study is not yet open for participant recruitment.

    So they have filed the paper work to start the trial, but the have not started enrolling people in the trial.
    I consider a trial to start, when they start recruiting patients for it (not when they file the paper work).
    Some people, especially researchers, consider that the trial starts when they put in the paperwork, but that's not how I do it, now. (In the past, I did consider a trial to start when the ClinicalTrial.gov record was created, but I found that some of these records just sat there, and never became an active trial. So now I wait for recruitment to start.)

    For this trial in particular, they put in the paperwork almost 2 years ago. So this trial has been "quiet" (no forward progress) for all that time. It was not recruiting people when they filed the paperwork in January of 2013, and it still not recruiting now. As far as I know.

    Joshua Levy
     
  12. karri

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    So this step 2 device is also known as medtronic 640g. Just released in Australia. Video link: https://www.youtube.com/watch?v=wl6WDkxXjBc
     
  13. joshualevy

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    Yes, indeed! The 640g is "step 2" to an artificial pancreas (predictive insulin shut off to prevent low BG), and it is great news that it is available in Australia.

    For the previous "step 1" AP, it took US FDA 31 months to approve it after it had already been approved in Europe. (That's not a typo, even with over 2 years of experience in safety and effectiveness on Europeans, the FDA still did not approve this.) It will be interesting to see of the US FDA has learned anything about how to do better, or if they botch the step 2 approval much like they botched the step 1 approval. I very much hope they learned from their previous mistakes, but there is no way to tell, except to see how long it takes.

    Joshua Levy
     
  14. karri

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    Thinking about timelines(based on history)
    Veo (European name for 530g) came back in 2010
    640g available in 2015
    so medtronic seems to have 5-year cycle for pumps?

    medtronic 750g (step3) in 2020
    medtronic 860g (step4) in 2025
    medtronic 970g (step5) in 2030
    and lastlly
    medtronic 1080g (step6) in 2035...
     
  15. joshualevy

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    I'm not really an expert in Medtronic's product development cycle.
    Although, if I'm going to track APs in the marketplace, and they continue to lead the field, then I'm going to learn more about their product cycle. You might want to read up on wall street analysts's coverage of Medtronic. These guys work for stock brokerages, and my guess is that there are 5 or 10 who have covered Medtronic for years already, and some of their work will be publicly available. They should have product release dates going back years, so you can see if that 5-year cycle has been true in the past.

    Also, I'm not sure each step will be it's own device. For example, I think a company might skip step 3, and just come out with 4 after 2. Also, I think Medtronic might in the future feel pressure from start ups, who are trying to have their first product be a step 4, 5 or 6 pump.

    As an optimistic summary, in the past I've only needed to track scientific progress to track AP development, but it is now clear that I need to track commercial development as well, and that in itself is a great sign of forward progress.

    Joshua Levy
     
  16. karri

    karri Approved members

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    Josh, a heres photo from diatribes twitter feed;
    [​IMG]

    Takeaways;
    Minimed 640g (predictive glucose) EU 2015/US 2016
    Minimed 670g (Overnight closed loop system) EU 2018/US 2017
     

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