Possible Cures for Type-1 in the News (Mid Feburary)

Clinical Trial of Diamyd, Ibuprofen ("Advil") and Vitamin D

Diamyd (GAD65) is a protein which is one of the targets of the autoimmune attack that starts off type-1 diabetes. It was developed with the idea that giving it to people with type-1 diabetes would teach their immune systems to not attack their own beta cells. It would be like giving someone who is allergic to peanuts, just a tiny amount of the peanut protein that triggered their allergy, in the hopes that they would build up tolerance.

Unfortunately, although it worked in mice and (to some degree) in phase-II studies in people, it failed in phase-III studies in newly diagnosed type-1 diabetics.   There are still a couple of smaller on going studies.  For example, to see if Diamyd will help prevent type-1 in high risk people who have not yet been diagnosed with the disease.

So that brings us to this study. The idea behind it is:

1. Give more Diamyd vaccine than was given in the past. About twice as much.
2. The Vitamin D is supposed to stimulate the part of the immune system that reacts to the Diamyd vaccine, so it makes for a more powerful vaccination effect.
3. The Ibuprofen ("Advil") lowers the inflammation in the pancreas, which may help save beta cells, and may help the vaccine work better, and may do both.

The study will include 60 children (aged 10 to 18) in the honeymoon phase. They will be followed for 30 months, but expect some results after only 6 months. The participants will be divided into 4 groups of 15. One will be a placebo group, and the other three will each get different combinations of the three treatments.  Since they hope to start in February 2013, I think it is reasonable to expect the 6 month results in the second half of 2015 and the 30 month results by the end of 2017.  That's assuming it takes them 2 years to recruit 60 people.  I have not yet seen a clinical trials record for this, yet.

Press release: http://www.diamyd.com/docs/pressClip.aspx?section=investor&ClipID=738266

More About Diamyd

This is a full PhD thesis that was written based on data from Diamyd's phase-II clinical trial.
http://liu.diva-portal.org/smash/record.jsf?pid=diva2:562438
http://liu.diva-portal.org/smash/get/diva2:562438/FULLTEXT01

Imatinib ("Gleevec" / "Glivec") Starts a Phase-II Clinical Trial

This study has not yet started recruiting, but when it does, it will be a 66 person trial.  It is double blind and placebo controlled.   It is open to honeymooners (first 100 days), including children.  They hope to start in April 2013 and end by April 2017.  I"m not sure of the details, but I think patients will take a pill daily for the first year.  They will have clinic visits monthly for the first year, and twice a year thereafter.

Imatinib is a relatively new cancer drug, which is popular because it targets an enzyme that only cancer cells have, so it is relatively non-toxic to non-cancer cells.  (The buzzword is "targeted".)  The obvious question is why would it be expected to work on type-1 diabetes.   The work done so far in mice suggests that it is a different pathway entirely, which leads to it's effect against type-1.

Some background on why this might work (in order, earliest to most recent):
   Animal models 2007: http://www.fasebj.org/content/21/2/618.abstract
   More mice 2008: http://www.ncbi.nlm.nih.gov/pubmed?term=19015530
   Press release: http://www.ucsf.edu/news/2008/11/4166/cancer-drugs-type-1-diabetes
   Human tissue 2011: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0024831

Notice the progression, and the speed:  First tested in animals in 2007.  First tested in people in 2013.  And remember: this is for a drug that is already approved, for another disease!

Wikipedia: http://en.wikipedia.org/wiki/Imatinib
Clinical Trial Record: http://www.clinicaltrials.gov/ct2/show/NCT01781975

Vitamin D Starts a Phase-II Clinical Trial

So far, there is no evidence that Vitamin D can cure or treat type-1 diabetes, and only a little evidence that it can prevent the disease.  This trial is trying to cure or treat type-1 diabetes by giving Vitamin D during the honeymoon phase.

The trial is being done in Nationwide Children's Hospital (Columbus, Ohio, USA) by Dr.Kathryn J Stephens and Dr. Robert P Hoffman.  It has not started enrollment, but they plan to enroll 54 people.  Half will get vitamin D for 9 months, half will get a placebo.  They hope to have results in March 2014.

I had previously reported on a vitamin D trial, but that was a population based trial, not an intervention trial.  This is an intervention trial, which are typically much higher quality. 

Clinical Trial Record: http://www.clinicaltrials.gov/ct2/show/NCT01724190

A Note About Terminology

I know that some people are very emotional about saying "a person who has type-1 diabetes" vs. saying "a type-1 diabetic", as in "they gave the drug to five people with type-1 diabetes" vs. "they gave the drug to five type-1 diabetics".  Some people object strongly to the second form, because they think that it defines the person by the disease; that it signals in some way that the disease is the person or the person is the disease.

Personally, I usually use the first form, because I prefer it and because I know that some people really object to the second form.  But I'm not fanatical about it, and you will occasionally see me refer to "type-1 diabetics".  I'm not trying to insult anyone when I use the second form.

Joshua Levy
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF or JDCA news, views, policies or opinions. My blog contains a more complete non-conflict of interest statement.   Thanks to everyone who helps with the blog.
Clinical Trials Blog: http://cureresearch4type1diabetes.blogspot.com
Cured in Mice Blog: http://t1dcuredinmice.blogspot.com/

DiaKine starts Phase-I clinical trials on Lisofylline (LSF)

DiaKine is about to start it's first clinical trial in a research program aimed at curing type-1 diabetes. Their treatment is Lisofylline (LSF), an anti-inflammatory drug that (in NOD mice) has prevented type-1 diabetes and (when given with exendin-4) cured existing type-1 diabetes.

Previously (in May 2008) DiaKine has formed a joint project with Kinexum Metabolics, to run a human trial (phase-II) using both of their drugs together (LSF and INGAP). The combination had already given good results in NOD mice. That trial was supposed to start in "late 2008". Kinexum Metabolics has since changed it's name to Exsulin (not INsulin, but EXsulin. Get it?) I can't find any record of the LSF+INGAP trial starting, but each company is testing it's own stuff seperately, so maybe after that, they'll test them together. I know a lot of people are interested in an anti-inflammatory and a beta-cell growing combination therapy, and obviously these two companies are interested in that, also. In any case, this trial is LSF only, not the combo they talked about earlier.

The current trial involves 8 people, and is supposed to start in May 2009 and be done by December 2009.

This research is being done in New Jersey.

You can read a news article here:
http://www.earthtimes.org/articles/show/diakine-therapeutics-diabetes-immune-modulator-drug-set-for-human-clinical-trial,821004.shtml

The US FDA's clinical trial record is here:
http://clinicaltrials.gov/ct2/show/NCT00896077

And the official press release is here (and is better than most):
http://www.diakine.com/assets/news20090512.pdf

The press release talking about LSF+INGAP together is here:
http://www.diakine.com/assets/news20080506.pdf

I want to thank the Wainscoat family for bringing this to my attention.

Joshua Levy

Atorvastatin (Lipitor) in New Onset Type 1 Diabetes Mellitus

This is a "new to me" study, that actually started in July 2007 and is expected to end July 2010. It is phase-II and included 54 people, who are within 6 weeks of dx for type-1 (so honeymooners only). 2/3 of the people will get Atorvastatin (Lipitor) and will be compared against the 1/3 who don't get the drug.

The US clinical trial record is here: http://www.clinicaltrials.gov/ct2/show/NCT00529191

Now, for those of you who did a double take, when you saw that Lipitor was involved: Yes, this is the same statin drug which is used to lower cholesterol, and is the best selling drug in pharmaceutical history. There was no phase-I study for this treatment, because they knew the drug was safe, they went straight to phase-II.

Apparently, Atorvastatin (Lipitor) results in lower insulin requirements when give to "rodent models". I assume they are talking about NOD mice. I'm not sure why this drug might work, but it does lower inflamation, so maybe that's it.

I know of one study which gave Atorvastatin (Lipitor) to people with established type-1 diabetes in the hopes it would limit artery damage. It was not successful. However, I don't see that those guys reported A1C, BG, or insulin usage numbers turning the trial:
http://www.freundpublishing.com/Journal_Pediatric_Endocrinology_Metabolism/JPEM22p65.pdf
Of course, the studies are focused on different time frames, honeymoon vs. non-honeymoon so they may well come to different results.

Joshua Levy

Two New Trials to Test Kineret / Anakinra

I recently found out about two clinical trials into the drug Kineret also known as Anakinra (an Anti-Interleukin-1 treatment). A phase-I study which started in March 2008, and a phase-II study which started in January 2009. Last year there was some interest in the idea that inflammation was a causative factor in type-1 diabetes. These are the first human trials that I know of which are based on attacking inflammation to try to cure type-1 diabetes (in honeymooners only, however). This drug is already approved by the US FDA for the treatment of rheumatoid arthritis. It has also already be used in clinical trials focusing on type-2 diabetes and some autoimmune diseases (in addition to RA).

The phase-I study is 15 kids (aged 6 to 18) who are within one week of diagnosis. The trial is scheduled to end in July 2009. It is being done by Soumya Adhikari at Children's Medical Center Dallas, Texas, United States, and is funded by their own foundation. You can read the US Clinical Trail Record here: http://clinicaltrials.gov/ct2/show/NCT00645840. I can find no other information on this trial on the web.

The phase-II study is being done by the Steno Diabetes Center in Denmark is testing using Kineret on newly diagnosed type-1 diabetics. The study is called "AIDA". It is multi-site, all in Europe. You can read more about it here: http://www.aidastudy.org. The study is funded by JDRF, Steno, and Oresund.

This is their description of the drug:

Kineret® is already being used in the treatment of patients suffering from arthritis and studies are now suggesting that it may also be useful for patients with Type 1 diabetes. The active substance in Kineret is interleukin-1 receptor antagonist, a blocker of an immune-signal molecule named interleukin-1. During inflammation this blocker is produced by your body to limit tissue damage caused by inflammation, and kineret is an exact copy of this naturally occurring molecule.

The study will use 160 patients, starting in January 2009 and ending (they hope) in September 2011. Half will get the drug, half placebo. After 80 patients have been followed for 6 months, they will do analysis on the available data, and decide if it is worth continuing the trial, and if it is safe to do so. I don't know if this interim analysis will be published or not. (I hope so!)

Patients will inject themselves once a day, for two years, so this is a pretty big commitment on their part. Since patients must be 18 or over, and with in 12 weeks of diagnosis, I suspect it will take them quite a while to enroll 80 people, even as they have 23 sites participating. Although the fact that it is using an already approved drug should make it easier to recruit.

The US Clinical Trial Record for this is NCT00711503, which you can see here: http://www.clinicaltrials.gov/ct2/show/NCT00711503

There is more information on the Steno center here: http://www.stenodiabetescenter.com/documents/home_page/document/index.asp

If you are newly diagnosed (less than 12 weeks), and in Europe, here is a list of trial sites:
http://www.aidastudy.org/centers/index.htm

A Little Discussion

Everyone knows that type-1 diabetics have a lot of inflammation in their pancreas and especially around their beta cells. Most researchers believe that inflammation is a result of the body's immune attack on it's own cells. That is, the underlying immune problem causes inflammation and also causes beta cells to die (which causes the symptoms of type-1 diabetes). However, some researchers believe that the underlying immune problem causes inflammation, and that this inflammation kills the beta cells, which causes the symptoms of type-1. The difference is that, in the second model, if you stop the inflammation you can stop the symptoms of type-1 diabetes (the high BG numbers and the low numbers). And that is a big difference. But this second model is still a minority opinion.

The treatment being tested should lower inflammation, so if the second model is correct, it will lessen the symptoms of type-1 diabetes, maybe remove the symptoms entirely: the body will naturally produce more insulin. In any case, one of the great things about this research, is that we should have some solid data soon. The phase-I trial should complete mid this year, the early data from the phase-II later this year, and the final data from the phase-II by year after next.

Joshua Levy