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 carin.andren_aronsson@med.lu.se
Clinical Trial Registry: https://clinicaltrials.gov/ct2/show/NCT04014660
Discussion
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 d5894@mail.cmuh.org.tw
Contact: Hung-chih Lin 886-4-22052121 ext 4640 d0373@mail.cmuh.org.tw
Principal Investigator: Chung-hsing Wang
Clinical Trial Registry: https://www.clinicaltrials.gov/ct2/show/NCT03880760
Discussion
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:
https://www.visbiome.com/pages/about-us
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 t1dinfo@mcw.edu
Clinical Trial Registry: https://www.clinicaltrials.gov/ct2/show/NCT04141761
Earlier Study Clinical Trial Registry: https://www.clinicaltrials.gov/ct2/show/NCT03423589
Discussion
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 hallemj@peds.ufl.edu
Contact: Miriam Cintron 352-273-5580 cintrm@peds.ufl.edu
Clinical Trial Registry: https://www.clinicaltrials.gov/ct2/show/NCT03961854
Clinical Trial Registry: https://www.clinicaltrials.gov/ct2/show/NCT03961347
Discussion
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: https://www.clinicaltrials.gov/ct2/show/NCT03556631
Probiotics in Newly Recognized Type 1 Diabetes
Clinical Trial Registry: https://www.clinicaltrials.gov/ct2/show/NCT03032354
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.
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