Thursday, November 20, 2014

Extra Reading


JDCA "State of the Cure" Update

Each year the JDCA (Juvenile Diabetes Cure Alliance) puts together a summary of cure research.  As a JDCA fellow I contributed information to this effort, although I did not help write the report.  In my opinion, it's a excellent document, well worth reading.  It's only about 15 pages long.  In addition to scientific information on a cure, it also includes information on money: how it's raised, who spends how much, etc.

http://www.thejdca.org/wp-content/uploads/2014/11/SOTC-2014-Final.pdf

JDRF Slide Show On Prevention

This is a great slide show put together by Jessica Dunne who is the Director of Discovery Research for the Juvenile Diabetes Research Foundation.  It is 12 slides.  In addition to material on possible viral and microbiome ("gut") triggers of type-1, it also includes data on growth in type-1 diagnosis, genetics, and so on.

http://www.tudiabetes.org/forum/attachment/download?id=583967%3AUploadedFile%3A3546968


Joshua Levy
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.

Saturday, November 15, 2014

Artificial Pancreas Update (Nov 2014)

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:
  • Schneider Children's Medical Center of Israel, Contact: Moshe Phillip, PhD + 972 3 9253747 mosheph@post.tau.ac.il
  • University of Ljubljana, Faculty of Medicine, Contact: Tadej Battelino, PhD +386 1 5229235 tadej.battelino@mf.uni-lj.si
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-pathway-to-an-artificial-pancreas-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/

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/2014/10/21/1-million-nih-grant-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%20Pancreas

Group
FDA
Phase
JDRF
Step
Average BG
Estimated A1c
Size
Adolescents?
Duration
AP Use
Boston University
II
6
138
6.4
53
Yes5 days24 Hours/Day
Cambridge
II
3
146
6.7
17
No
8 days24 Hours/Day
MD-Logic
II
3

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

Medtronic
III
2
Just
Started
184
Yes
2 days
24 Hours/Day

Rensselaer
Not
Started



Joshua Levy 
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.

Wednesday, November 5, 2014

Beta-O2 Starts a Phase-I Trial (and an update on encapsulated beta cells generally)

Introduction to Encapsulated Beta Cells

Encapsulated beta cells are implanted devices.  The encapsulation coating allows blood sugar in, and insulin out, but does not allow the body's immune system to attack the beta cells. It also allows nutrients in and waste products out. This allows the beta cells to naturally grow and to react to the body's sugar by generating insulin which goes into the body's blood system. Meanwhile, the body's autoimmune attack cannot target these beta cells, and you don't need to take any immunosuppressive drugs (as you would for a normal beta cell transplantation).  The cells inside the coating are human beta cells, and different companies get their beta cells from different sources.

Beta-O2 Starts a Phase-I Clinical Trial

Beta-O2 is starting a phase-I clinical trial of their "ßAir Bio-Artificial Pancreas" (encapsulated beta cell) device as a possible cure for type-1 diabetes.  The devices itself is similar to other encapsulated beta cell devices (ie. Diabcell by LCT, Encaptra by ViaCyte, etc.) with one important difference: the device is injected with oxygen once a day.  This is a manual step performed by the patient.  The company claims it will take about 2 minutes, and provides pictures of the device used, which looks like a needle attached to tubing.  You can read about the device here: http://beta-o2.com/living-with-sair/

The clinical trial is pretty standard for a phase-I trial: 8 people will use the device for 6 months, and be followed for an additional 6 months.  They will test for safety and effectiveness (C-peptides, Insulin usage, and A1c numbers), and hope to finish in March 2016.

The clinical trial is being run by the Uppsala University Hospital.  Contact information is: Per-Ola Carlsson, MD, PhD  Phone number:  +46 18 4714425  Email:  Per-Ola.Carlsson@mcb.uu.se.  This trial is for adults with long established (5 years or more) type-1 diabetes.  One unusual requirement for this trial is that patients must start out using 1 unit of insulin per day per kilo of weight (or less).

The clinical trial is expected to cost about US$ 1 million, with JDRF paying for half.

Press release: http://www.fiercemedicaldevices.com/press-releases/first-patient-successfully-implanted-safetyefficacy-study-beta-o2s-air-bio
Clinical Trial Record: http://clinicaltrials.gov/ct2/show/NCT02064309

Other Encapsulated Beta Cells Research Underway

Interest in encapsulated beta cells seems to be cyclical.  When my daughter was first diagnosed, about 10 years ago, encapsulated beta cell devices were a strong area of research.  But one by one, most of the devices failed.  We then went through several years with only one company (LCT) in human trials.  Now, however, interest appears to be picking up with a new generation of human trials underway.  Here is a quick summary of the encapsulated beta cell devices that I know of:

Beta-O2: Just started a phase-I clinical trial.
Viacyte: Just started a phase-I clinical trial.
LCT: Has been doing phase-II trials for several years, but has not made any forward progress (in terms of better results), in years.
Hospital St. Luc research project: Completed (?) a phase-I trial, but not sure about any progress recently.
AZ-VUB: In phase-I, but I don't know any details.
DRI Biohub: Started clinical trials for infrastructure for such a device, but still using immunosuppression.
Sernova: Started clinical trials for infrastructure for such a device, but still using immunosuppression.
Islet Sheet Project: In animal testing.
Harvard Project: In animal testing (?).
Chicago Diabetes Project: Still using immunosuppression.
Nuvilex: Starting animal testing soon.

In my opinion, these are a lot of different research groups, all focused on the same type of cure.  For me, that's good news, because it suggests that many people believe this technology is ready to lead to a cure.  And that makes me optimistic.  Unfortunately, previous "waves" of encapsulated beta cell devices did not lead to a cure, so that makes me nervous.

Background Information

http://en.wikipedia.org/wiki/Cell_encapsulation
https://www.landesbioscience.com/pdf/HunkelerPDF.pdf

Joshua Levy 
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.

Friday, October 24, 2014

Type-1 and Obstructive Sleep Apnea


A reader of this blog asked me what I knew about the relationship between Obstructive Sleep Apnea (OSA) and Type-1 Diabetes.  I didn't know anything, but over the last few weeks, I've been looking through the research.  There is not a lot, but what there is, I've summarized here.

The sound track for this posting is Bon Jovi's I'll Sleep When I'm Dead:
http://grooveshark.com/#!/s/I+ll+Sleep+When+I+m+Dead/wu1oT

This is an area where it is important not to mix up type-2 and type-1 diabetes, and to remember that people who say "diabetes" almost always mean "type-2 diabetes".  One of the more common causes of OSA is being overweight, and this is also one of the more common causes of type-2 diabetes (although in neither case is it the only cause).  The result is that OSA is highly correlated with type-2 diabetes.

However, there has been a little research on type-1 diabetes and Obstructive Sleep Apnea (OSA), and that is what I'm focusing on here.

But first, a little background on OSA:
http://en.wikipedia.org/wiki/Obstructive_sleep_apnea
http://www.webmd.com/sleep-disorders/guide/understanding-obstructive-sleep-apnea-syndrome

Question 1: How common is OSA?

Simple Answer: about 5% of the general population, and about twice that in people with T1D.

Detailed Answer: The overall rate is about 4% [r2] or 5.7% [r4] of the population, but the rate for people who have T1D is about 10% [r3] or 12.7% [r4].  One study [r6] found that sleep apneas were much more common in type-1 diabetics, than in type-2 diabetics.  Study [r8] found high levels of sleep apneas in people with type-1 diabetes, but had no comparison group.

Question 2: Is OSA a danger sign for people who have T1D?

The [r4] study found no connection between sleep issues and HbA1c numbers.  But [r5] found that patients' poor glycemic control and worse apneas were correlated (but no way to tell which caused the other, or if they were both caused by something else entirely). The "Sleep and Glucose Regulation in Youth With Type 1 Diabetes Mellitus" study [r7] is clearly based on the idea that bad sleep results in worse BG control.  Their data shows a clear correlation, but again,I don't see a causal direction.  Although it seems reasonable to me to think that if you BG was out of range, that would cause sleeping problems, rather than the other way around.

Question 3: Is OSA an early warning signal of T1D?

While there is no question that OSA can be an early warning sign of type-2 diabetes, I was not able to find any studies suggesting that it was an early warning sign for type-1.

Question 4: Does OSA cause T1D?
Question 5: Does T1D cause OSA?

I could not find any research on these questions.

Ongoing Studies

There is only one related clinical trial currently running.  They are comparing people who have type-1 diabetes to those without, and are investigating relative rates of OSA, type-1 issues which might cause OSA, and OSA impacts on complications of type-1.  The study includes 145 people, and is expected to be completed in Sept. 2016.  They are recruiting in Paris, France.
Clinical Trial Record: http://clinicaltrials.gov/ct2/show/NCT01935765

There is another small study at the University of Arizona, where students with type-1 will be asked to extend their sleeping hours.
Clinical Trial Record: http://clinicaltrials.gov/ct2/show/NCT01739712

My Summary

My basic conclusion from all this, is that there is very little research in this area.  Based on what we have, it looks like OSA is much more common in people who have type-1 diabetes than in others, and maybe even more common in people with type-1 than type-2 diabetes.   This is a major change in perspective, since OSA is traditionally associated (in people's minds) with type-2 diabetes. Unfortunately, almost nothing else is known about the causality or effects of OSA in people who have type-1 diabetes.

References

[r1] http://en.wikipedia.org/wiki/Obstructive_sleep_apnea
[r2] http://www.webmd.com/sleep-disorders/guide/understanding-obstructive-sleep-apnea-syndrome
[r3] http://www.ncbi.nlm.nih.gov/pubmed/21679352
[r4] http://www.ncbi.nlm.nih.gov/pubmed/21573904
[r5] http://www.ncbi.nlm.nih.gov/pubmed/10907113 (this study uses the term "insulin dependant diabetes", but they are clearly studying children, so I'm assuming they are type-1)
[r6] http://www.ncbi.nlm.nih.gov/pubmed/4004160
[r7] http://www.ncbi.nlm.nih.gov/pubmed/22215921  mass media report here:
http://www.medpagetoday.com/Endocrinology/Diabetes/30460 and clinical trial record here:
http://clinicaltrials.gov/ct2/show/NCT00848822
[r8] http://www.endocrinology.dk/index.php/spor-24-blandet-endokrinologi/488-96-prevalence-of-sleep-apnea-in-danish-type-1-diabetes-patients



Joshua Levy 
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, JDCA, or Tidepool 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.

Thursday, October 16, 2014

Three Unsuccessful Trials


This blog posting summarizes several clinical trials aimed at curing type-1 diabetes which have failed.  These are never fun, happy blog postings, but they are important.  One of the big problems with trying to understand research based on mass media reporting is that failures are rarely covered at all.  The soundtrack for this posting is "Down" by Melissa Lambert:
http://grooveshark.com/#!/s/Down/4BHhwn

Sitagliptin and Lansoprazole Unsuccessful in Phase-II Trial

This was a combination therapy.  The researchers were attempting to combine a drug to stop the autoimmune attack and another drug to trigger beta cell growth.  Both drugs were approved for other purposes, and commonly used.  Unfortunately, it didn't work.  Summary from abstract:
At 12 months, the mean change in C-peptide area under curve was −229 pmol/L for the treatment group and −253 pmol/L for the placebo group; this difference was not significant (p=0·77).
Abstract: http://www.sciencedirect.com/science/article/pii/S2213858714701159
Blog at start of trial: http://cureresearch4type1diabetes.blogspot.com/2010/08/possible-cures-for-type-1-in-news-mid.html

Pioglitazone Unsuccessful in Phase-I Trial

Pioglitazone has been approved for use in type-2 diabetes for over 10 years. It is part of a larger drug family called thiazolidinediones which have been shown to preserve beta cells in animals with type-1 diabetes, and to reduce death of beta cells in petri dishes.  It was being tested as a honeymoon cure, but did not pan out:
Conclusion: In this pilot study, pioglitazone did not preserve β cell function when compared to placebo.
Article: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3890222/
Previous blogging: http://cureresearch4type1diabetes.blogspot.com/search/label/Pioglitazone

Stop Covering Lisofylline

As far as I can tell, no one has done human trials of this treatment for over two years, so I'm going to stop considering it as a possible cure, unless something new comes to light.  Lisofylline is an anti-inflammatory.

Previous coverage (one blog posting) is here:
http://cureresearch4type1diabetes.blogspot.com/search/label/Lisofylline


Joshua Levy
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, JDCA, or Tidepool 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.

Thursday, September 25, 2014

VC-01 by ViaCyte Starts a Phase-I Clinical Trial

Some people are horrified at the idea of curing diseases by using embryonic stem cells.  If you are one of those people, stop reading now!  This posting is all about curing type-1 diabetes using human embryonic stem cells.  In the future, you should skip over all my blog postings with the tag VC-01 or ViaCyte.

ViaCyte (previously known as Novocell) has started a phase-I clinical trial for their encapsulated beta cell product, which is called VC-01.  This device is designed to cure type-1 diabetes.  The encapsulation coating allows blood sugar in, and insulin out, but does not allow the body's immune system to attack the beta cells. It also allows nutrients in and waste products out. This allows the beta cells to naturally grow and to react to the body's sugar by generating insulin which goes into the body's blood system. Meanwhile, the body's autoimmune attack can not target these beta cells, and you don't need to take any immunosuppressive drugs (as you would for a normal beta cell transplantation).  The cells inside the coating are human beta cells, grown from human embryonic stem cells.   Here is the company's official diagram:



This Trial

This trial will enroll 40 adults who have had type-1 diabetes for over 3 years.  There is no control group, but some people will get two implants while others will get 4 or 6 implants.  C-peptide will be measured after 6 months, and safety issues will be tracked for 2 years.  They hope to finish in August 2017.

Patients are being recruited now in San Diego, California, USA, and they plan to add more locations in the future.

Clinical Trial Record: http://clinicaltrials.gov/ct2/show/NCT02239354
ViaCyte Page: http://viacyte.com/products/vc-01-diabetes-therapy/
Twitter Traffic: https://twitter.com/hashtag/viacyte

Discussion and Opinions

Encapsulated beta cells seem like a straight forward cure for type-1 diabetes, but companies have been working on them since the 1990s, without creating a cure.  There appear to be several difficult problems to solve, especially getting oxygen to the new cells.   Bottom line is this: while encapsulated beta cells sound like a "just needs engineering" cure for type-1 diabetes, decades of work has not led to a cure yet, so it is obviously harder than it looks.

Finally, ViaCyte is very well funded.  In the last few months, they have gotten over $16 million from CIRM, $20 million from Johnson and Johnson, $5 million in venture capital, and half a million from JDRF.

Similar Work

LCT's Diabcell is similar to ViaCyte's VC-01, in that they are both encapsulated beta cell devices. They do use different encapsulation coatings, and Diabcell uses pig beta cells, while VC-01 uses beta cells grown from human embryonic stem cells.  LCT has been tested in people for over 6 years, and is currently in phase-II trials.  (At one time it had approval to be sold in Russia, but it never was sold there.) There is also a device being tested at the University Clinical Hospital Saint-Luc in Belgium, which uses human beta cells (from cadavers) and a different encapsulation coating. 

Several organizations are doing animal tests on various encapsulated beta cell devices.  These include Cerco Medical, Beta-O2, DRI, and several more.

Finally, several organizations are doing human tests on beta cell devices which are not (yet) encapsulated, but they hope to encapsulate in the future.  DRI is doing work like this, as is Serova.  If beta cells are not encapsulated, then you must take immunosuppressives for the rest of your life, so I don't consider those a cure, yet. However, if they then progress to the point where immunosuppressives are not needed, then they would be a cure.

Terminology Note

Some of the news coverage refers to VC-01 as an "artificial pancreas", however I only use that term for electro-mechanical devices.  I use the term "encapsulated beta cells" for devices like VC-01.  You might also hear people refer to it as a "bioartificial pancreas".

If you care about the stem cell production method, here is the company's diagram:


Joshua Levy 
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, JDCA, or Tidepool 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.

Wednesday, September 17, 2014

JDRF Funding for a Cure 2014

In the US, we are in the "Walking Season" when JDRF asks us to walk to raise money for a cure. So I'd like to do my part, by reminding you all of how important JDRF is to the human trials of potential cures for type-1 diabetes, which I track.

Let me give you the punch line up front: 70% of the treatments currently in human trials have been funded by JDRF. (And the number is 71% for the later phase trials) This is a strong impact; one that any non-profit should be proud of.  This summary does not include Artificial Pancreas research or stem cell growth trials, because there are so many of those that it would be hard to include them all. For a recent summary of some (not not all) AP research, please read this blog posting: http://cureresearch4type1diabetes.blogspot.com/2014/07/ada-2014-type-1-diabetes-cure-research.html

Below is a list of all the potential cures, grouped by phase of trial that they are currently in, and separated into potential cures that JDRF has funded, and potential cures that JDRF has never funded.

This list is a list of treatments, and many of these are being tested in more than one clinical trial.  For example, the "ATG and autotransplant" treatment is actually running three trials, but since they are all testing the same treatment, it is only one item in the list.  The list below uses the following marks to show the nature of the treatments:
    (Established) One or more trials are open to people who have had type-1 diabetes for over a year.
    (Prevention) This treatment is aimed at preventing type-1 diabetes, not curing it.

Also remember that I give an organization credit for funding a treatment if they funded it at any point in development; I don't limit it to the current trial.  For example, JDRF is not funding the current trials for AAT, but they did fund earlier research into it, which helped it grow into human trials.  I include indirect funding of various kinds.  For example, the JDRF funds nPOD and helps to fund ITN and several other organizations, so I include research done by these other groups as well, as being indirectly JDRF funded.

Cures in Phase-III Human Trials
Summary: currently there are no treatments aimed at curing type-1 diabetes which are in phase-III trials (under the definition of cure that I use).  This is the second year in a row there have been no phase-III trials underway, and it's not a good thing.  Even worse, I don't see a phase-III study starting even next year.  However, phase-III trials grow out of phase-II trials, and there was big growth in the number of phase-II trials this year.  I'm very hopeful that in a few years, these will naturally result in a number of phase-III trials.

Cures in Phase-II Human Trials
Summary: there are 21 trials in phsae-II, and 15 of them have been funded by JDRF, while 6 have not. Here are the treatments that have been funded by JDRF:
  • AAT (Alpha-1 Antitrypsin) by Grifols Therapeutics and also Kamada 
  • Abatacept by Orban at Joslin Diabetes Center
  • Abatacept by Skyler at University of Miami (Prevention)
  • Aldesleukin (Proleukin) at Addenbrooke’s Hospital, Cambridge, UK
  • Diabecell by Living Cell Technologies  (Established)
  • Diamyd, Ibuprofen ("Advil") and Vitamin D by Ludvigsson at Linköping University
  • Gleevec by Gitelman at UCSF
  • Oral Insulin (Preventative)  
  • Rituximab by Pescovitz at Indiana
  • Stem Cell Educator by Zhao (Established)
  • Teplizumab (AbATE study team)
  • Teplizumab by Herold/Skyler/Rafkin (Preventative)
  • Umbilical Cord Blood Infusion by Haller at University of Florida
  • Ustekinumab by University of British Columbia
  • Xoma 52 by Xoma Corp  (Established)
Not funded by JDRF:
  • ATG and autotransplant by Burt, and also Snarski, and also Li
  • Atorvastatin (Lipitor) by Willi at Children's Hospital of Philadelphia
  • BCG by Faustman at MGH  (Established)
  • Brod at University of Texas-Health Science Center
  • Secukinumab by Novartis Pharmaceuticals
  • Vitamin D by Stephens at Nationwide Children's Hospital  (Prevention)
Cures in Phase-I Human Trials
Summary: there are 19 trials in phase-I, and 13 of them are funded by JDRF, while 6 are not. Here is the list funded by JDRF:
  • Alefacept by TrialNet
  • ATG and GCSF by Haller at University of Florida  (Established)
  • ßAir bio-artificial pancreas by Beta-O2's at Uppsala University Hospital in Sweden (Established)
  • TOL-3021 by Bayhill Theraputics   (Established)
  • CGSF by Haller at University of Florida
  • Trucco at Children’s Hospital of Pitt / Dendritic Cells (DV-0100) by DiaVacs   (Established)
  • IBC-VS01 by Orban at Joslin Diabetes Center
  • Leptin by Garg at University of Texas
  • Lisofylline by DiaKine
  • Nasal insulin by Harrison at Melbourne Health  (Prevention)
  • Polyclonal Tregs by both Trzonkowski and Gitelman 
  • Pro insulin peptide by Dayan at Cardiff University
  • VC-01 by Viacyte (Established)
Not funded by JDRF:
  • CGSF and autotransplant by Esmatjes at Hospital Clinic of Barcelona  (Established)
  • Encapsulated Islets at University clinical Hospital Saint-Luc   (Established)
  • Etanercept (ENBREL) by Quattrin at University at Buffalo School of Medicine
  • Monolayer Cellular Device  (Established)
  • Rilonacept by White at University of Texas
  • The Sydney Project, Encapsulated Stem Cells  (Established) 
Summary of all Trials
40 in total
28 funded by JDRF
So 70% of the human trials currently underway are funded (either directly or indirectly) by JDRF. Everyone who donates to JDRF should be proud of this huge impact; and everyone who works for JDRF or volunteers for it, should be doubly proud.

Just Looking at Trials on Established Type-1 Diabetics
13 of these treatments (33%) are being tested on established type-1 diabetics.
Of these, 8 are funded by JDRF
So 62% of the trials recruiting established type-1 diabetics are funded by JDRF.

Compared to Last Year
In 2013 there were 37 treatments in clinical trials, in 2014 there are 40 (growth of 8%)
In 2013 there were no treatments in Phase-III trials, in 2014 there are none (no change).
In 2013 there were 15 treatments in Phase-II trials, in 2014 there are 21 (growth of 40%).
In 2013 there were 22 treatments in Phase-I trials, in 2014 there are 19 (drop of 14%).

How I Count Trials for This Comparison
  • I give an organization credit for funding a cure if it funded that cure at any point in it's development cycle.
  • I mark the start of a research trial when the researchers start recruiting patients (and if there is any uncertainty, when the first patient is dosed).  Some researchers talk about starting a trial when they submit the paper work, which is usually months earlier.
  • If there are different clinical trials aimed at proving effectiveness as a cure and as a preventative, or effectiveness in honeymooners and established diabetics, then those are counted separately.
  • For trials which use combinations of two or more different treatments, I give funding credit, if the organization in the past funded any component of a combination treatment, or if they are funding the current combined treatment. Also, I list experiments separately if they use at least one different drug.
  • The ITN (Immune Tolerance Network) has JDRF as a major funder, so I count ITN as indirect JDRF funding.
  • I have made no attempt to find out how much funding different organizations gave to different research. This would be next to impossible for long research programs, anyway.
  • Funding of research is not my primary interest, so I don't spend a lot of time tracking down details in this area. I might be wrong on details.
  • I use the term "US Gov" for all the different branches and organizations within the United States of America's federal government (so includes NIDDK, NIAID, NICHD, etc.)
  • I don't work for the US Gov, JDRF, or any of the other organizations discussed here.  I have a more complete non-conflict of interest statement on my web site.
Some Specific Notes:
  • The FDA's clinical trials web site lists two studies being done on Cyclosporine and Lansoprazole ("Prevacid") as a combination treatment.  These trials were listed over 18 months ago but not started recruiting patients.  I have not included them in my list of clinical trials. 
  • LX4211: This drug is a SLGT2, and I don't think it is likely to be a cure.  It might turn into a treatment that can be paired with insulin for better results, but not a cure.
  • Serova's Cell Pouch and DRI's BioHub: These two clinical trials are both testing one piece of infrastructure which might be used later in a cure.  They are testing a part of a potential cure.  However, in both cases, the clinical trials being run now require immunosuppression for the rest of the patient's life, so I'm not counting them as testing a cure.
  • INGAP: This treatment was in human trials twice, but long in the past.  The current testing is being done by a high school student, and I'm not counting it as cure research until I see better results than were seen before (and which previously led nowhere).
  • GABA
This is an update and extension to blog postings that I've made for the previous five years:
http://cureresearch4type1diabetes.blogspot.com/2013/10/jdrf-funding-for-cure-2013.html
http://cureresearch4type1diabetes.blogspot.com/2012/09/jdrf-funding-for-cure-2012.html
http://cureresearch4type1diabetes.blogspot.com/2011/10/jdrf-funding-research-for-cure-2011.html
http://cureresearch4type1diabetes.blogspot.com/2010/09/jdrf-funding-research-for-cure-2010.html
http://cureresearch4type1diabetes.blogspot.com/2009/09/jdrf-funding-research-for-cure.html
http://cureresearch4type1diabetes.blogspot.com/2008/10/jdrf-funding-of-cure-research-phases-ii.html

Finally, please remember that my blog (and therefore this posting) covers research aimed at curing or preventing type-1 diabetes that is currently being tested in humans.  There is a lot more research going on, not covered here.

Please think of this posting as being my personal  "thank you" note to all the JDRF staff, volunteers, and everyone who donates money to research a cure for type-1 diabetes:
Thank You!

Finally, if you see any mistakes or oversights in this posting, please tell me!  There is a lot of information packed into this small posting, and I've made mistakes in the past.

Joshua Levy
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, JDCA, or Tidepool 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.