Tuesday, May 26, 2015

Mesenchymal Stromal Cell Results From a Phase-I Trial

Mesenchymal Stromal Cells (MSC) are the stem cells in your bone marrow.  Stems cells can grow into beta cells, and some researchers think they can modulate the immune system (they generate one or more chemicals that cause the immune system to stop attacking beta cells).  So it's possible that stem cells might resolve both cure issues at once.  They might be able to regenerate beta cells and stop the autoimmune attack.  That is what these researchers hope.

Results From a Phase-I Trial

These researchers, at Uppsala University Hospital in Sweden, ran a phase-I trial, randomized and with a control group, but not blinded.  There were 10 people in the treated group, and 10 in the control group.  MSCs were harvested from a patient, treated externally, and then put back in that same patient.  No immunosuppression was used, and I don't think the people were ever hospitalized (the work was done in a clinic).  Data was collected on insulin usage, A1c, fasting C-peptide, and post meal C-peptide, among other measures.

Fasting C-peptide measures how much insulin your body is generating as background. It's measured while fasting, usually first thing in the morning.  This is your natural basal insulin. Post meal C-peptide measures how much insulin your body is generating in response to carbohydrates.  It's measured after eating a meal with a known carbohydrate content. This is a body's natural insulin bolus.

My summary of the results are as follows. In all cases the paper is comparing data measured 10 weeks after the treatment (which the paper considers starting or baseline data) to data measured 1 year after treatment (which the paper considers resulting data):
  1. Fasting C-peptide, A1c, and insulin usage did not significantly change for either group, and there was no significant differences between the groups.
  2. Post meal C-peptide levels for the untreated group dropped about 12%.  Dropping is bad, but it's also normal during the honeymoon phase.  In the treated group, C-peptide numbers rose 5-10%, and that represents improvement.  The difference between the two groups was statistically significant.
  3. There were no safety issues.
Discussion and Opinions

Confirming that the procedure was safe is a good thing, of course, and is the official goal of a phase-I trial.  But this is a procedure that's been done for decades to treat other diseases (especially cancer), so no surprise that it is safe.

I was a little surprised at how consistent the insulin usage, A1c numbers, and fasting C-peptide numbers were.  I assumed that A1c would still be high from diagnosis and would drop, and that insulin usage would rise to the end of the honeymoon, and that fasting C-peptide would drop.  None of that happened during the course of the honeymoon.

The important results are the post meal C-peptides.  For this data, higher numbers are good, because they mean the body is generating more of it's own insulin.  In untreated people those numbers dropped about 15%, which is normal for the first year after diagnosis.  The treated people saw a rise in their C-peptide.  There is no doubt that is good news, but it did not have an impact on the treated people. Specifically, they were still injecting the same amount of insulin, and their A1Cs did not improve.  So it's a small effect.

My memory is that I've seen this level of result several times, for several different drugs, over the last two years or so.  I think I was much more excited about them in the past.  Part of my lack of excitement is that the treatments with these results that I saw a few years ago have not progressed. They don't give better results in more recent studies.  That might be because the research is taking longer than expected, or it might be that getting a small result is much easier than getting a useful (to patients) result.  But in any case: I haven't seen forward progress in other treatments with similar initial results, so I've become less excited about these kinds of results, in general.

So in general, these results go in my "good start, but more is needed" category of results.

This study was published on line Sept-2014 and on paper in Jan-2015:

Clinical trial record: https://clinicaltrials.gov/ct2/show/NCT01068951

Joshua Levy
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, May 8, 2015

Artificial Pancreas Update (May 2015)

I have decided, for 2015 at least, to do quarterly updates for Artificial Pancreas research. The area is moving forward so quickly that I think that quarterly updates are warranted.

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. Most people do not consider this a cure, but I follow AP research because some people do consider it a cure.  There is no doubt that such technology would be a huge step forward in treatment, and would largely prevent "dead in bed" due to low blood glucose events.

An earlier version of this blog had the wrong dates for future Medtronic product releases.  I'm sorry about that.  This posting has the correct dates.  Thanks to Tamar Sofer-Geri for finding the mistake.

Artificial Pancreas Update for April 2015

The JDRF uses a 6 step model to describe milestones on the way to the fully featured artificial pancreas that we all want.  You can read about those milestones here: http://jdrf.org/research/treat/artificial-pancreas-project/.
So when I refer to "step 1" and "step 4" and so on in this blog, I'm referring to the steps described by JDRF.

Corporate News from Medtronic

Back in January, Medtronic made the following product announcements:
  • The 640G (predictive low glucose suspend) will ship in Europe in April 2015.
  • The 640G will ship in the United States in April 2016.
  • The 670G will ship in the United States in April 2017.
  • The 670G will ship in Europe in April 2018.
News (from Close Concerns / diaTribe): https://www.closeconcerns.com/knowledgebase/r/ce9abf26

There are three pieces of good news included in those predictions.

First, the 640G is a step 2 Artificial Pancreas, so it will predict and avoid low blood glucose events.

Second, the 670G (depending on exactly how it turns out) could be a step 3 or 4 device.  That means it will predict and avoid both low BGs and high BGs, but not cover meals automatically.

Third, it means that Medtronics believes that the FDA's previous approval delays will stop:

  • There was a 2.5 year delay (from European approval to US approval) for the 530G.
  • Medtronics expects a 1 year delay for the 640G.
  • Medtronics expects a 1 year advantage (US before Europe) for the 670G.

I hope they are right about this!  FDA's delays in earlier AP approvals are one of the major reasons AP development has been slow, and European availability is ahead of us. If the FDA is able to fix this problem over the next few years, that is a huge piece of good news for all AP companies and ultimately, all AP users.

MD-Logic Goes Commercial

MD-Logic is one of the artificial pancreas projects which has been in phase-II clinical trials.  I previously blogged on it in Nov-2014: http://cureresearch4type1diabetes.blogspot.com/2014/11/artificial-pancreas-update.html
In the past, it has been a research project, but a company called DreaMed Diabetes was founded to commercialize it, and they recently signed an agreement with Medtronic.  According to diaTribe:
Medtronic plans to use this technology in their artificial pancreases after the 670G.  The 670G will be a step 4 AP (automatic except for meals), while the MD-Logic based follow on will be a step 5 AP (automatic including meals).

Also, MD-Logic's blood glucose control algorithm got a "CE" mark in Europe (which is their "approval to sell" symbol).  You can read about it here:
However, I'm not sure what that means from a practical point of view.  You cannot use an algorithm by itself.  It has to be part of a piece of software or hardware, and right now no one is selling any product which uses the algorithm.  Maybe this CE mark will speed Medtronic's approval in Europe when the time comes?

Artificial Pancreas News From Tandem (makers of t:slim)

I slogged through a Tandem analyst's call in Feburary, which you can read here:

There are only a few paragraphs on AP research, and my rough translation of them is this:

Tandem is currently experimenting internally, and not on people, with both predictive low glucose suspend (step 2 AP) and predictive high glucose dosing (step 3 AP).  In the second half of 2015 they will start the paperwork to run a clinical trial testing predictive low glucose suspend.  Based on discussions with the FDA at that time, they will have  better idea of how many clinical trials will be required for approval (and therefore how long it will take).  Also they will have a better idea about testing both the predictive low suspend and high dosing at the same time, or release one and then the other.

Bihormonal AP Update from CarbDM's Diabetes Summit

I attended CarbDM's "Diabetes Summit" in Silicon Valley last month.  It was wonderful, even though I could not stay to the end.  Listening to the morning speakers was very informative, but in this blog I'm going to limit myself to discussing  Dr. Ed Damiano's talk.

Dr. Damiano is working on a bihormonal (insulin and glucagon) AP, called the "Bionic Pancreas". The key piece of information from his talk was that they will finish the current round of phase-II trials on April 27th (that's the last day of data collection).   Another round of studies is planned for the second half of 2015.  For next year, the plan is to create a device that can be sold and spend the rest of 2016 and 2017 testing it.

Dr Damiano reported on results from several clinical trials (adults and children who use the AP under different circumstances).  For all these studies, the numbers were great (in my opinion).  They averaged in the low 140s or high 130s in different trials.

There were some other interesting tidbits: the daily dose of glucagon used by people on this bihormonal AP was between 1% and 3% of the dose used in a single "rescue" injection, so a relatively small amount.   Also, the amount of insulin used by people on the AP was about the same as people in the control group.  So it's clear that the bihormonal AP is using insulin more efficiently, not just using more insulin.

CarbDM's: http://carbdm.org/
The Diabetes Summit: http://carbdm.org/summit/

International Conference on Advanced Technologies & Treatments for Diabetes (ATTD 2015) 

This was a conference held in Feburary in Europe that had dozens of papers, many of which covered artificial pancreas research, continuous glucose monitoring techniques, and related areas.

You can see all of their posters here:
Abstracts for a huge number of papers are here:

Joshua Levy 
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.