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	Yes	5 days	24 Hours/Day
Cambridge	II	3	146 6.7	17	No	8 days	24 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.