Possible Cures for Type-1 in the News (May)

Phase-I Study of Of Gluten Free Diet In Honeymoon Type 1 Diabetes (Diabglut)

This trial will recruit 160 children, aged 3 to 18.  It started in December 2015, and is expected to end in December 2020. Half of the people will be put on a gluten free diet within one month of diagnosis, and the other half will not (and will be the control group).

This study is being done in Skanes University Hospital, Lund, Region Skane, Sweden, 22185
Contact: Annelie Carlsson, MD PhD    +46768267170    annelie.carlsson@med.lu.se
Contact: Iren Tiberg, PhD, nurse       iren.tiberg@med.lu.se

Clinical trial registry: https://clinicaltrials.gov/ct2/show/NCT03037190

Discussion

My first thoughts when I saw this study were: "Why do a study like this?  Does anyone really believe that a gluten free diet will cure/improve type-1 diabetes?"

The researchers included four previous studies as references for this work, but I think the one that mattered was this one:
https://www.ncbi.nlm.nih.gov/pubmed/22729336
This is the case study of a single patient (a five year old boy).  He was was put on a gluten free diet a few weeks after diagnosis, and remained off insulin for 20+ months.  That's an unusually strong honeymoon, and I think it is reasonable to say that the researchers are hoping that they can create that kind of honeymoon in other newly diagnosed people.

For me, case studies (like this one) represent a middle ground between anecdotes and scientific studies.  I don't think they are very strong by themselves, but I do think that following them up with a research study is a good way to proceed.

The other three studies cited by the researchers as background for this research were much less dramatic. One study tried delaying introduction of gluten in the diet of babies: no effect. Another tried putting people with two antibodies on a gluten free diet before diagnosis: no effect on eventual diagnosis, but might have a small effect on beta cell survival after diagnosis. The third study was population based, and suggested that introducing gluten earlier (at 4 months, rather than later) might lower the rate of celiac diagnosed at 12 years. As a population study, I don't put a lot of weight on it, and the impact was to celiac and not type-1, in any case.

Minimal Islet Transplant at Diabetes Onset (MITO)

This is mostly a transplant trial, so I don't expect to follow it moving forward, but it is a different type of transplant, so I'm describing it here.

Most transplants are done on the most seriously impacted people with type-1 diabetes.  These people often have a lot of trouble controlling their type-1, they are often already having serious complications, and are generally on the worst side of the type-1 spectrum.  These are the people who often volunteer for transplantation.

This study is targeting the opposite: people who within 6 months of type-1 diagnoses, and are still generating some residual insulin.  The idea is to transplant some islet cells in combination with ATG, G-CSF, and Rapamycin treatments. It's a "kitchen sink" approach.  All of those treatments are in active clinical trials right now, but none of them has been shown effective so far.

I do think that it will be valuable to get data from people who are not so extremely sick when they get their transplant, although I doubt this will lead to a cure in the short term.

They are recruiting 6 people in Italy:
IRCCS San Raffaele Scientific Institute   Milan, Italy, 20132
Contact: Lorenzo Piemonti, MD   0226432706 ext 39    piemonti.lorenzo@hsr.it
Contact: Paola Maffi, MD       paola.maffi@hsr.it
Contact: Emauele Bosi, MD 0226432818 ext 39 emanuele.bosi@hsr.it

Clinical trial registry: https://clinicaltrials.gov/ct2/show/NCT02505893

T-Rex Now Can Enroll People 8 Years Old, and Older

Previously, they could enroll people as young as 12, but they have enough safe results with those kids, so that the FDA will now allow kids as young as 8 to enroll. You can read all about the technique they are using and who is eligible in my previous blogging:http://cureresearch4type1diabetes.blogspot.com/search?q=T-Rex

Also, the last time I blogged, this study was only recruiting in two locations, but now they are recruiting all over the US, from Oregon to Connecticut to Florida to UCSF, not to mention Tennessee, Missouri, Massachusetts, Indiana, and that is not a complete list.  (See the Clinical Trial Record, link below, to get a complete list.)

This is a phase-II trial which is a follow on to the previous "Polyclonal T-Reg" study, which I also blogged about here:
http://cureresearch4type1diabetes.blogspot.com/search/label/Polyclonal%20Tregs
(Look at all the postings in this link, except the first one, in order to see the history of this treatment.)

Clinical Trial Record: https://clinicaltrials.gov/ct2/show/NCT02691247

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.

Gluten Free Diets To Prevent or Cure Type-1 Diabetes

One of my policies in blogging has been that I don't "play favorites".  I don't blog on something because I think it is a good idea, nor do I refuse to blog on something because I think it is a bad idea. I try to blog on all clinical trials which are aimed at curing type-1 diabetes no matter if I personally think they will be successful or not.  That is why I'm writing this blog on various researchers trying to cure type-1 diabetes with a gluten free diet.

Introduction

There is general consensus that celiac disease and type-1 diabetes are related conditions, in that people having one are noticeably more likely to get the other.  Many researchers think that both are autoimmune diseases and that they share some genetic susceptibility, so that that someone genetically more likely to get one is also more likely to get the other.

The standard treatment for celiac disease is a gluten free diet.  Since many of the bad effects of celiac disease are triggered by gluten in the diet, reducing or eliminating gluten can dramatically reduce symptoms.

Therefore, some researchers have looked at the possibility that a gluten free diet might help type-1 diabetics as well.  The rest of this blog discusses this research, divided into two sections: Completed Studies (everything until about 2012) and Underway Studies (basically 2013 - on).

My discussion is at the end.

Completed Studies

From 1999: Gluten-free diet prevents diabetes in NOD mice.

NOD mice (the standard animal model of type-1 diabetes) were given either gluten-free or normal diets.  The diabetes rate in the normal diet was about four times higher than in the gluten-free mice, and the if they did get diabetes, the gluten-free mice got it later in life.  Both effects were statistically significant.

Abstract: http://www.ncbi.nlm.nih.gov/pubmed/10585617

From 2011: Gluten Free First Year Does Not Prevent Type-1 Diabetes

This study involved 150 babies.  Half started eating gluten normally (at 6 months).  The other half delayed gluten until 12 months.  All of the babies had a family history of type-1 diabetes and a genotype (called HLA) which raised their chances of getting type-1 diabetes.

These children had their autoantibodies measured at 3 years and their type-1 diabetes status measured at 10 years.  The results were the same in both groups, so a gluten free first year did not prevent or delay either autoantibodies or actual onset of type-1.

Abstract: https://www.ncbi.nlm.nih.gov/pubmed/21515839

Clinical Trial Record: https://clinicaltrials.gov/ct2/show/NCT01115621

From 2012: Remission without insulin therapy on gluten-free diet in a 6-year old boy with type 1 diabetes mellitus.

This is a single case study (not a clinical trial), but it generated the interest in gluten free diets reflected in the clinical trials currently underway.  These doctors reported on the case of one newly diagnosed type-1 diabetic who immediately went on a gluten free diet, and did not need to inject insulin after that.  This patient was followed for 20 months, and did not need to use insulin during that time.  The doctors in this case were of the opinion that the gluten free diet had extended the length and strength of his honeymoon remission.  The patient was a 5 year old boy, and tested positive for the GAD autoantibody.

Abstract: http://www.ncbi.nlm.nih.gov/pubmed/22729336

Underway Studies

Gluten Free Diet Starts a Phase-I Honeymoon Trial

This trial will enroll 20 people between 2 and 18 years old within 3 months of diagnosis.  All will eat a gluten free diet; there is no control group. C-peptides and insulin usage will be measured after 1 year to see if a gluten free diet results in slower or less loss of beta cells or less need for injected insulin.

This study is being run by Jannet Svensson, PhD at the Copenhagen University Hospital in Herlev, but is already fully enrolled.  She was one of the authors of the case study listed above.  This study started in March 2012 and has already finished.  It has been submitted for publication, but I have no news yet on when it will be published.

Clinical Trial Record: https://clinicaltrials.gov/ct2/show/NCT02284815

Gluten Free Diet Starts a Phase-II Prevention Trial

This trial will enroll 60 people between 2 and 50 years old who have one or more autoantibodies, but are not showing other symptoms of type-1 diabetes.  Half will eat a gluten free diet and half will eat a normal diet, while both groups will get Vitamin D, Omega 3 fatty acids, and probiotics. C-peptides will be measured throughout the trial to see if a gluten free diet results in slower or less loss of beta cells.

If you are interested in enrolling, you can contact  Dr. Helena Elding Larsson at Lund University, Department of Clinical Sciences Malmö, Sweden, 20502

Clinical Trial Record: https://clinicaltrials.gov/ct2/show/NCT02605148

Gluten Free Diet Starts a Phase-II Honeymoon Trial

This trial will enroll 60 people between 1 and 17 years old within 4 months of diagnosis.  Half will eat a gluten free diet and half will eat a normal diet. C-peptides will be measured after 1 year to see if a gluten free diet results in slower or less loss of beta cells.

The trial started in March 2015 and should end in March 2017 (meaning they should be finished with enrollment right about now: March 2016).  If you are interested in this study you can contact  Dr. Eba Hathout at Loma Linda University, California.

Clinical Trial Record: https://clinicaltrials.gov/ct2/show/NCT02605564

Discussion


Somehow I think that if gluten free diets could prevent or cure type-1 diabetes, someone would have noticed before now.  There are human populations, such as Inuit (Eskimos) and Masai, who have naturally gluten free diets.  If this theory were correct, these populations would have low or nonexistent rates of type-1 diabetes, and that would have been noticed by now.  Also, in the early 1900s (prior to the discovery of insulin) one of the common type-1 life prolonging diets was essentially gluten free, but it did not cure type-1 diabetes, either.

My basic summary is that right now, if you look at clinical trials (and ignore case studies and animal research), there is one published study, and it was unsuccessful.  In the next few months we will get one more, and two additional results in the next two years or so.  That will be a total of four studies, and should be enough to answer the question (or at least show a strong trend).

Obviously, the optimism about gluten free diets is generated from the case study.  It does appear that the child had type-1 diabetes (and was not a misdiagnosis).  I say that because they detected GAD antibodies, a marker for type-1 diabetes, and also because the researchers involved were (and are) heavily involved in type-1 research.  I just don't see them making a misdiagnosis error.  Going insulin free for 20 months after diagnosis is certainly very unusual.  Going insulin free for a short period of time after diagnosis does happen.  And we do not know how long the longest honeymoon period is. However, even taken together, 20 months insulin free is highly unusual.  Of course, the gluten free diet could just be random chance.  (That is, not causation, not correlation, but just lucky chance.)  But it is exactly the kind of coincidence that should be followed up on, and these four studies are a strong follow up.

One final point I want to make: often times I hear proponents of alternate medicine complain that their theories are ignored by mainstream medicine. Specifically they say that drug based treatments are pushed in preference to diet based treatments, so that drug companies profit.  The research described here is a strong counter example.  Given a single case study showing a diet based therapy might work, mainstream researchers have launched three clinical trials in an attempt reproduce the result.  The results will speak for themselves.

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.