Sunday, December 22, 2019

Clinical Trials Using Probiotics For Type-1 Diabetes

Some people believe that the gut microbiome (bacteria in your digestive system) can impact type-1 diabetes.  If true, that would mean that type-1 diabetes might be cured, prevented or delayed by changing your gut microbiome, and one way to do this is to give people probiotics in the hope that it will improve their gut microbiome.

This blog posting is a general update on all the probiotic clinical trials aimed at curing, preventing, or delaying Type-1 Diabetes that I know of.  The research included here uses several different bacteria.  If you know of any more, please tell me, so I can update this posting.

An important part of all the trials that I discuss below, is that they have a control group so we can compare what happens to people who get probiotics to those who don't.   This is important because right now, a lot of people eat probiotics (foods which contain these bacteria), so it is hard to know what effects these have.  By comparing groups that got them to control groups that did not, these studies should provide better information than the anecdotes (personal stories) we have now.

Five Trials Currently Underway

Trial #1: Prevention of Autoimmunity With Lactobacilli

Patients will get a daily pill containing two "good" bacteria: Lactobacilli plantarum and Lactobacilli paracasei in the hope that it will delay or prevent the onset of type-1 diabetes.

This trial is open to anyone who tests positive to one autoantibody associated with type-1 diabetes, celiac disease, or thyroid disease.  They will recruit 200 people.  Half will get treatment and half will get a placebo and be a control group.  The trial is randomized and blinded.

Each person will be followed for one year.  The primary end point is the number of autoantibodies they are positive for at the end of the study.  Remember, everyone starts with at least one to enter the trial, so the question is, how many more do they accumulate in a year?  They started recruiting in Oct-2019 and hope to finish in Dec-2021. 

This trial is being done at one location in Sweden:
Clinical Research Center, Malmö, Sweden, 20502
Contact: Carin Andrén Aronsson, PhD    +46 40 391113    

Clinical Trial Registry:


This is a prevention/delay study (not a cure or a treatment study).  That is why it is measuring number of autoantibodies as an end point.  It is the quickest measurement which might give a signal that T1D has been avoided or delayed.  Furthermore, it is now well established that just about everyone who has two autoantibodies will eventually get T1D.  People in this study start out with one, so even those who gain only one more, end up at two, and are almost certain to eventually be diagnosed with T1D.

For me, the open question is, how many people in this study will have type-1 diabetes?  Because they are recruiting people with autoantibodies from any one of three different diseases, it is not clear to me how many people will be in the T1D part of the trial.  Given the short time period (just 1 year), and unknown number of people in the T1D part of this trial, I'm worried they will not have enough data to answer the question.

For comparison, the Teplizumab study which also tested to see if T1D could be delayed or prevented, included 76 people (all had T1D) and ran for 5 years, which means the whole study was about 380 person-years.  The maximum this study could possibly have is 200 person-years, and that is assuming everyone has T1D (no one has celiac disease or thyroid disease).  If the three diseases are recruited evenly, then there will only be about 66 person-years in the T1D arm, making it about 1/6 as big as the Teplizumab study.

Trial #2: The Effect of Probiotics on Type 1 Diabetes Mellitus in Children

This study is giving children with established type-1 diabetes three probiotics: Lactobacillus salivarius, Lactobacillus johnsonii, and Bifidobacterium lactis for six months.  This is a phase-II study from my point of view, enrolling 80 people with randomization and a control group.  Primary outcome measurements are A1c and fasting BG measurements.  Secondary outcomes include measures of inflammation and internal immune response.

They started in Aug-2018 and hope to finish in July-2021.

This study is being done in Taiwan:
    China Medical University Hospital, Taichung, Taiwan, 40447
    Contact: Chung-hsing Wang    886-4-22052121 ext 4640  
    Contact: Hung-chih Lin    886-4-22052121 ext 4640  
    Principal Investigator: Chung-hsing Wang   

Clinical Trial Registry: 


Because this study does not measure C-peptide as a primary or secondary outcome, I don't consider it cure focused, and so won't follow it long term, unless the immune results suggest that it might be a path to a cure.  However, it will tell us if probiotics can help people who have T1D better manage their blood sugars and A1c numbers, and I know many people are interested in that.

Trial #3: Probiotics in Newly Diagnosed T1D

This is the follow-on study to a previous phase-I/pilot study.  Unfortunately, that previous study was tested on people who did not have T1D.  So I would describe this study as a phase-II? study: it is the size of a phase-II trial, but does not have T1D results from a phase-I trial behind it.  The probiotic being studied is a commercial product called Visbiome made by ExeGi Pharma.  You can read more here:

This study will enroll 60 honeymooners and follow them for 3 years.  The study is blinded and 40 will get the treatment while 20 get a placebo and be a control group.  The primary end point is a measure of inflammation, while the secondary end points include C-peptides, gut bacteria measures, and more measures of inflammation.

They started in April-2019 and hope to finish in Jan-2025.

This study is recruiting now at one site:
    Medical College of Wisconsin, Milwaukee, Wisconsin, United States, 53226
    Contact: Susanne Cabrera, MD    414-955-4903    

Clinical Trial Registry:
Earlier Study Clinical Trial Registry:


This is the only study that has C-peptide as a end point, so it is the only one that can be said to focus on finding a cure to T1D.

Trials #4 and $5: Lactobacillus Johnsonii 

These two studies are identical, except that one enrolls adults who have had T1D for less than 3 years, while the other enrolls children and adolescents who have had T1D between 4 months and 2 years.  Both studies will enroll about 60 people in a randomized and blinded study lasting just under a year.

Unfortunately, the only primary outcome is a measure of side effects, and there are no secondary outcomes listed in the clinical trial registry. 

Both studies start in Oct-2019 and should end in July-2020.

Both of these trials are recruiting at one site:

UF Clinical Research Center, Gainesville, Florida, United States, 32610
    Contact: Michael Haller, MD     352-273-9264    
    Contact: Miriam Cintron     352-273-5580

Clinical Trial Registry:
Clinical Trial Registry:


Because these studies do not measure C-peptides, autoantibodies, A1c, or BG numbers, by themselves, they are not going to provide information on a cure, prevention, delay or even a treatment of T1D.  The best they can do is clear the way for a follow-on trial(s) with cure focused end points.

Trials In The Future:

There are two more studies which are listed in the Clinical Trials registry but have not yet started recruitment.  Both are getting old, and I'm worried that they might never start, or conversely that they have already started, but the researchers have not updated the Clinical Trials registry:

Effect of Live Combined Bifidobacterium and Lactobacillus on Glycemic Control and Other Outcomes in Type 1 Diabetes
Clinical Trial Registry:

Probiotics in Newly Recognized Type 1 Diabetes
Clinical Trial Registry:

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.

Tuesday, December 3, 2019

Avotres's AVT001 Starts A Phase-I Trial

AVT001 is an "autologous dendritic cell therapy" meaning that a person's own dendritic immune cells are taken out, processed in some way, and then put back.  Dendritic cells can be thought of as the immune systems "sensors".  They detect foreign invaders and then communicate that knowledge to other types of immune cells (especially T cells).

This trial flows out of some work done at Columbia University.  Basically, researchers there found a defect in a specific type of immune cell called a HLA-E–restricted CD8+ T cells.  They believe that this defect leads to the immune system attacking the beta cells in the pancreas and causing type-1 diabetes.  The researchers found this defect in many (but not quite all) people with type-1 diabetes, but not in people who did not have the disease.  They also found a way to fix the defect in the immune cells.

The basic technique being tested here is to take out dendritic cells from the patient and treat those cells so that when they are put back into the patient, they (in turn) fix the defect in the HLA-E–restricted CD8+ T cells, which leads to type-1 diabetes.

This Study

The trial will enroll 24 people in two groups, treatment and control.  Everyone will be in their honeymoon (diagnosis within the last year), and everyone will be tested to make sure they have the immune cell defect the researchers are targeting.  The treatment group will get three dendritic cell treatments.  Everyone will be followed for 5 months, and they hope to have primary results by Nov-2020, which is quick for a human trial.  However, they will continue to gather data until June-2022.

There are three primary end points for this trial, and all are safety related.  Two are measures of adverse effects and the third checks for changes in blood chemistry.  They also have three secondary endpoints.  These include C-peptide and A1c numbers, which will give an indication if the treatment is working, and an immune measurement, which will give some insight into the mechanism by which it works.   

They are recruiting at the Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, USA.  Contact information is:
Jason Gaglia, MD 888-813-8669

Trial Registration:
Trial Site Web Page:
Paper describing the basis for this trial:
Commentary on that paper:


Although both treatments involve dendritic cells, this research is not related to Dr. Trucco's previous work, which I have blogged about in the past.

This trial is sponsored by Avotes Inc.  However, I can not find any useful information on the company or their technology.  So I'm vague on the details.  As far as I can tell, Avotes does not have a corporate web page, and there are no web pages which describe in any detail what the treatment involves, which is very unusual for a clinical trial.

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.