Saturday, July 16, 2016

Polyclonal T-Regs Start A Phase-II Trial (T-Rex)

T-Rex is a phase-II study of polyclonal T Regulator ("T-Reg") cells.  It is a follow on study to work done at UCSF and in Poland which I've blogged about in the past:

A quick summary of this treatment is as follows: remove one specific type of T regulator cell (called "CD4(+)CD25(+)CD127(lo)") from a person with type-1 diabetes.  Grow them out so you have about 500 times more, and then put them back in the same person.  Since regulatory T cells naturally regulate the body's immune system, and the patient now has more of them, the hope is that they will prevent the autoimmune attack which causes type-1 diabetes.

The Study

This study will enroll 111 people divided into three groups (low dose, high dose, and placebo). Patients must be between 12 and 17 years old and be honeymooners (within 100 days of diagnosis). They will be followed for two years.  The primary endpoint is C-peptide generation (the body making it's own insulin) after one year, while secondary endpoints are A1C, insulin usage, adverse effects, and C-peptide at two years.

The study started recruiting in February 2016 and is expected to finish in March 2020.

In previous studies, the treatment involves two trips to the clinic (the second being an overnight stay), about two weeks apart.

Currently, this study is recruiting in two locations, but they hope to add more in the future:

Fargo, North Dakota, United States, 58122
    Contact: Kathryn McEvoy    701-234-3722
    Contact: Vicki Oberg    701-234-6722
Sioux Falls, South Dakota, United States, 57104
    Contact: Lynn M Bartholow, BA    800-305-5059
    Contact: Alycia Brantz    605-328-1369


This is a study where speed of recruitment is going to directly impact how long the study takes. This study gathers data for 2 years, so all data will be collected 2 years after the last patient is recruited. However, recruiting 111 teenagers from just two (relatively low population) sites, such as Fargo, North Dakota and Sioux Falls, South Dakota is going to take years.   The sooner they can recruit from more places, and especially higher population cities, the sooner they can finish recruiting, and the sooner we can see if this works.

This study is sponsored by Caladrius Biosciences, Inc. in collaboration with Sanford Health (which is different than Stanford University).  Caladrius Biosciences is a small pharma company specializing in bringing cellular therapies to market.

The term "cellular therapy" refers to treatments that use whole cells.  Cellular therapy itself is a broad topic and can include stem cell therapies, cellular transplants, etc.  In this case it refers to cellular "self transplants" where the patient receives cells that originated inside himself, but have been processed (in this case, grown out) outside his body.

The Company's web site:
Newspaper Article:
Clinical Trial Registery:

The same group of researchers are planning to start a another trial, which will combine Polyclonal Tregs and IL-2.  I'll blog on that trial when it starts recruiting.

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.

Monday, July 4, 2016

Research In The News (July)

This is a combination of updates from the last month or two.

DILfrequency Completes Data Collection

In late may, the DILfrequency research team announced that they had finished collecting data, and were now starting to analyse that data.  Of course, that's great news, because it implies that results will be published in the next year or two.  (In my experience successful results are published within a year, unsuccessful results often take longer, if they are published at all.)

This study is testing Aldesleukin (also called Proleukin or IL-2) by giving it to adults within 5 years of diagnosis.  IL-2 is a component of the immune system, and they hope that more it will either improve or cure type-1 diabetes.  Are are looking for changes in the immune system which occurs quickly (ie. in a few weeks), or changes in insulin, A1c numbers, or C-peptide over a three month period.

I previously blogged on this study here:

These researchers seem to be months ahead of schedule.  Previously, they expected to finish data collection by October 2016, but they have actually finished in May 2016, which is a testament to their ability to recruit people with type-1 diabetes.  Even better, they enrolled more people than expected: 36 expected vs. 41 actual, that's 14% bigger than planned for.  This group is very media-savvy, with lots of tweeting, facebook posting, a pinterest page, etc.  I suspect that this media focus helped them recruit, and I hope it represents the future of clinical trial recruiting techniques.

New To Me: Cord Stem Cells In A Phase-II Clinical Trial

This trial started in 2009, but it registered with the US FDA's clinical trial registry in April 2016, and I did not know about it before then.  The basic plan is to give a total of 30 people a transplant of 3rd party umbilical cord stem cells (called allogeneic umbilical cord mesenchymal stem cells).  The people treated will be honeymooners (within 12 months of diagnosis), and must have had DKA when diagnosed.  There is no control group; everyone will get the treatment.  People will be followed for three years after transplant.  Primary outcome will be insulin usage, and secondary outcomes will be C-peptide, A1c, and autoantibody counts.  The researchers hope to finish collecting data in Dec 2019.

They are recruiting at one site:
Nanjing Drum Tower Hospital of Nanjing University Medical School. Nanjing, Jiangsu, China, 210008
Contact: Dalong Zhu, MD.PhD.    86-25-83106666 ext 61430  
Contact: Jing Lu, PhD.    86-25-83106666 ext 61431  

Clinical Trial Registry:


This research is similar to Haller's work at the University of Florida, which completed a phase-I and started a phase-II clinical trial also in 2009.  I've blogged on that research here:

Unfortunately, the phase-II study (which included a control group) completed in 2012 and was published in 2013, but was unsuccessful.  Exact quote was "Autologous UCB infusion followed by daily supplementation with vitamin D and DHA was safe but failed to preserve C-peptide.".

ATG Is Unsuccessful in a Phase-II Trial

58 people recently diagnosed with type-1 diabetes were given antithymocyte globulin (ATG) in the hopes that it would modulate the autoimmune attack on the pancreas's own beta cells.    The primary end point was C-peptide generation after 2 years (a measure of the body's ability to generate it's own insulin).  People who got the treatment did no better than people who did not.

Trial Registration:


Although there was no improvement if the researchers looked at everyone in the study, if the researchers only looked at older patients (between 22 and 35 years old), then they did see a statistically significant improvement in C-peptide levels as compared to untreated patients of the same age.  The researchers were hopeful that future testing might show that ATG is helpful for older patients.

Diabetes Care Has A Section On Artificial Pancreas Papers

You can read 9 AP papers in one place:
Diabetes Care is published by the ADA.

Losing Autoantibodies: Does It Happen And What Does It Mean?

It is now well established that people test positive for autoantibodies before they are diagnosed with type-1 diabetes, and (statistically) more autoantibodies are detected over time as people move closer to diagnosis.  Also, there is a big difference between having one autoantibody and having more than one.  I'm sometimes asked: can someone lose an autoantibody that they previously had?  Put another way, are autoantibodies a one way progression to type-1 diabetes? Or can people move closer or farther away from diagnosis (at least as measured by number of autoantibodies).

The answer, according to this paper:
is "its complicated".  Basically, some people do lose an autoantibody that they previously had and therefore, at least on paper, move away from type-1 diabetes.  However, in real life, most of the people who lose an autoantibody only had one to start with, and therefore were unlikely to ever be diagnosed with type-1 diabetes.  The people with more than one autoantibody (and who are likely to be diagnosed) rarely lose an autoantibody.

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.