Monday, August 13, 2012

Possible Cures for Type-1 in the News (early Aug-2012)


Prologue: Why Completing Enrollment is an Important Milestone for Clinical Trials

For two reasons.  First, because at that point it is possible to predict when the researchers will eventually finish collecting data.  The experimental design will say how long data will be collected for each person, so you can just add that duration to the date they finished enrollment, and that tells you when the final data will be collected.  Second, because much of the uncertainty that surrounds clinical trials involves recruiting participants, it is often unclear how hard it will be to get people, and long it will take.   But at this point, all that cunertainty is behind the researchers.  Once enrollment is complete, it is just gathering data, then analyzing data, and then publishing the data.  Researchers have a lot more control over those later stages, than over recruiting people in the first place.

Put another way, a clinical trial is made up of five tasks:
1. Do research to figure out what clinical trial should be done.  During this phase, the researchers are at the mercy of the science.  If they science doesn't pan out, then the experiment never gets done.
2. Get FDA approval for the clinical trial.  During this phase, the researchers are at the mercy of the FDA (or similar regulatory agency).  If they don't get approval, the experiment never gets done.
3. Recruiting patients.  During this phase, the researchers are at the mercy of the patients (or their parents).  If they can't get enough people to enroll, the experiment fails.
4.  Gathering the data.  During this phase, the researchers pretty much control their own destiny, unless a huge number of people drop out, or there is some unexpected safety issue.
5. Writing and publishing the results.  During this phase, the researchers are subject to editors and peer review (to some degree).  However, there are so many journals and web sites, that the researchers have many choices; they can even self publish, if all else fails.  They are not at the mercy of any one person or committee.

Completing enrollment is the end of phase 3 / start of phase 4, and you can see that researchers have a lot more control of their own destiny in phases 4 and 5, then in 1, 2, or 3.  

"REPAIR-T1D" (Lansoprazole and Sitagliptin) phase-II Study Completes Enrollment

This study finished enrolling in May 2012 and they plan to gather data for two years, so we should have results soon after May 2014.  This trail gives two currently approved drugs (Januvia and Prevacid) to type-1 diabetics within six months of diagnosis.  The hope is that it will restore or at least preserve beta cell function.

Press Release: http://www.newswise.com/articles/the-sanford-project-reaches-milestone-in-quest-to-cure-type-1-diabetes
Clinical trial record: http://www.clinicaltrials.gov/ct2/show/NCT01155284

GCSF/Neulasta phase-II Study Completes Enrollment

Previous blogging here: http://cureresearch4type1diabetes.blogspot.com/search/label/Haller

This study finished enrolling in March 2012, and they plan to gather data for two years, so we should have results soon after March 2014.  (Their clinical trial record says December 2014.) GCSF, also known as Neulasta or Pegfilgrastim, causes the body to generate it's own stem cells from bone marrow. These might rebalence the immune system or they might retrain it, but in any case, the hope is they will help cure type-1.

Burt's trial (the most successful so far) uses GCSF, ATG, and CZ. CZ is, by far, the most toxic of the three, so this trial can be viewed as "Burt ultra-lite". GCSF and ATG together would be "Burt lite" and there is a trial for that also ongoing.
Clinical Trial Record:   http://www.clinicaltrials.gov/ct2/show/NCT00662519

Thymoglobulin (ATG) Phase-II Study Completes Enrollment

Please read about Thymoglobulin (ATG) here: http://cureresearch4type1diabetes.blogspot.com/p/drugs-and-treatments-in-clinical-trials.html (scroll down the page until you see the section on ATG)

This phase-II study of ATG has completed enrollment.   It took them about 2 years longer than expected, so that's not good, but we can expect data collection to be complete in 2 years, and hopefully results will be published soon there after.  The ATG link about has complete information on why the researchers hope ATG might cure type-1 diabetes or be part of a cure.

Clinical Trial Record:  http://www.clinicaltrials.gov/ct2/show/NCT00515099
Previous blogging here: http://cureresearch4type1diabetes.blogspot.com/search/label/Gitelman

Combo (Diamyd, Lansoprazole and Sitagliptin) Trial Fails

This trial has a long and not so good history, which you can read in my previous blogging here: http://cureresearch4type1diabetes.blogspot.com/search/label/Combo

This Phase II study combined regenerative agents (lansoprazole and sitagliptin) and also Diamyd. The regenerative agents are both marketed drugs in the US. Diamyd is a vaccine like drug which trains the body's autoimmune system not to attack it's own cells.

This study's clinical trial record updated to show that it was terminated on 20 March 2012, although I think it had actually ended earlier.  Dr. Harlan, who started this study, had left the NIH, and the phase-III studies of Diamyd alone had failed or been canceled, so they decided not to pursue it.  

Obviously, it's too bad that it was canceled.  This was the first study that I knew of that attempted to combine a drug to stop the autoimmune attack and drugs to encourage the regrowth of beta cells.      I think that combining treatments like that is still a good thing to try, even if this specific combination did not work out.

Clinical Trial Record:  http://www.clinicaltrials.gov/ct2/show/NCT00837759

More Stable Glucagon

This is only vaguely related to a cure, but I thought I'd mention it.  Xeris is trying to create a form of glucagon which can be stored at room temperature for long periods of time.  From a cure point of view this is useful for an artificial pancreas (if you consider that a cure).  Simple APs are based on insulin alone.  However, there are more complex APs, which are based on insulin and glucagon.  Having a glucagon which was approved to sit in the pump for days, maybe weeks, would be important to these "bihormonal" APs.

As a nice side effect, it would mean that emergency glucagon needles could be preloaded, just like insulin pens, which would make them much easier to actually use in an emergency.  It also would make mini-glucagon doses much easier to administer, for those who use them.

You can think of an insulin only AP sort of like a car with a break but no accelerator.  The engine "revs high" and you run along.  You use the break to slow up.  A bihormonal AP (insulin and glucagon) is more like a car with a break and an accelerator.  More control.  The analogy is not perfect, but that's the basic idea.

Press Release: http://www.marketwatch.com/story/xeris-pharmaceuticals-awarded-phase-i-ii-nih-sbir-fast-track-grant-to-advance-stable-non-aqueous-glucagon-for-bi-hormonal-artificial-pancreas-2012-07-31

Why Pharma/Med Device Co's Apply for Approval in Europe FIRST

If you haven't read this blog posting by Scott Strumello, you should!  It compares the approval process for medical devices in the EU to the same process in the US:
http://blog.sstrumello.com/2012/08/why-pharmamed-device-cos-apply-for.html

Next Up: Results from Dr. Faustman's Phase-I BCG Trial

She published in PLoS last week, so I hope to blog about it in a week or two.

Joshua Levy
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF or JDCA news, views, policies or opinions. My blog contains a more complete non-conflict of interest statement.
Clinical Trials Blog: http://cureresearch4type1diabetes.blogspot.com
Cured in Mice Blog: http://t1dcuredinmice.blogspot.com/

7 comments:

pdx_dc said...

Just wanted to share with you (that you may need for the next blog post)

http://asweetlife.org/a-sweet-life-staff/featured/faustman-lab-research-how-excited-should-you-be/28902/

thanks
pdxmom

pdx_dc said...

I am not sure if you've covered this before but I found it very interesting - please watch!

http://www.sernova.com/i/video1/index-v1.html

Also, some other interesting things I have found

http://www.ncbi.nlm.nih.gov/pubmed/22814331

http://phys.org/wire-news/106582663/jdrf-helmsley-charitable-trust-to-fund-islet-encapsulation-resea.html

pdxmom

neononio said...

I just wanted to let you know that i appreciate you coverage. I can relate to your compassion as i am very obsessed with the care of my daughter with T1. I guess you have the same kind of background motivating you. There are a lot of us out here.

Unknown said...

Found this article posted on 3 july 2012, it's something from Europe and might be interesting. Thanks for all the blogging effort and keeping me up to date on what's going on in the world of science concerning my disease!

the link: http://www.montesquieu-instituut.nl/9353000/1/j9vvhfxcd6p0lcl/vj0w4ighkizz?ctx=vg9pl2emdcyl&tab=2

It refers to this effort against T1D: http://naimit.eu

It seems the last update was somewhere around november 2011 (they do annual updates). Maybe there is something new in there? I could not find anything concerning NAIMIT on your blog

Unknown said...

(I'm Unknown from above).

Their latest paper: http://www.ncbi.nlm.nih.gov/pubmed/22484814

Suprisingly readable

Joshua Levy said...

pdx_dc: I've previously blogged on Serova here: http://cureresearch4type1diabetes.blogspot.com/search/label/Sernova
but I don't think their current clinical trial is really on the path to a cure. It just holds a transplant in one place, and you still need to take immune suppression drugs for the rest of your life. I don't view that as a cure: you are trading insulin for immune suppression. Now, when they start testing sertoli cells, that's different!

Joshua

Joshua Levy said...

Unknown: that research was done on animals, so I will enter it in my "Cured in Mice" blog when I get a minute (after finishing the Dr. Faustman post that I'm working on now). This blog is for clinical (human) trials, that blog is for animal cures:
http://t1dcuredinmice.blogspot.com/

Joshua