Friday, February 15, 2013

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/

7 comments:

Wendy Rose said...

As always, thank you for providen such current, relevant information in language I can understand!

Any thoughts on the recent dog news?
http://www.the-scientist.com/?articles.view/articleNo/34394/title/Dogs-Cured-of-Type-1-Diabetes/

And, my daughter doesn't care either. Nor do I. "She has brown eyes." "She is brown-eyed." Whatever ;)

Joshua Levy said...

My comments on cures which have worked in animals always start out the same:
1. Very few cures in animals are ever even tried on people. They don't translate.
2. Of the cures that are tried in people, most fail.
3. Human clinical trials take 10-15 years, so if they start human trials tomorrow, and they work (both unlikely), then we will need to wait 10-15 years.

Basically, these researchers used two different gene therapies (given at the same time), to cause the body to regenerate cells that generate insulin in response to sugar in the blood.

With that in mind, this research does look promising, but it does have two weaknesses that will need to be addressed:

First, the dogs they used were not "naturally" diabetic, and did not have autoimmune diabetes of any kind. They were made diabetic by poisoning their beta cells, so that the cells died. My single biggest worry is that the autoimmune attack in type-1 diabetes would turn around and attack these newly genetically-changed cells.

Second, they used gene therapy. No gene therapy has ever been approved for use in the US. Obviously, that's a big problem, because it is always hardest to be first, when it comes to government approvals. Of course, we've got 10+ years of clinical trials in front of us, so hopefully some gene therapies will be approved in that time. But at the moment: zero is zero. The situation is better in the European Union where one gene therapy has been approved (in 2012). Note that although approved, this therapy is not yet generally available, even in Europe. They are hoping for late 2013.

One sentence summary: Might be fun to follow, but don't hold your breath!

Stalina Dsouza said...
This comment has been removed by a blog administrator.
Phuong Hoang said...

Thank you so much for updating the trial! I check your blog everyday because my daughter was diagnosed with type 1 since November. Your hard work is appreciated.

Valentin ANDREI said...

"The situation is better in the European Union where one gene therapy has been approved (in 2012)."

Please, could you tell me what therapy your are talking about?

off this topic: yesterday I saw an article about "Pancreate", a product bought by Sanofi from CureDM, for 365 mil Eur in 2009 (http://en.sanofi.com/Images/13732_20100410_curedm_agreement_en.pdf)

In 2009 everybody was talking about this product as it cured all type 1&2. Sanofi bought it for a lot of money, and since 2009...no article, no news, nothing about this product. Do you know something about this?
Thank you!

mylene sai said...
This comment has been removed by a blog administrator.
Valentin ANDREI said...

@bellefire, could you tell us please what it means "rapidly"?
Relating to your hope I do not think there will be a cure for healing because it is not desired (the business is much higher. If someone will find something they will be bought and forgotten. All injections will probably be replaced with other gadgets, but that does not mean healing, but the prosperity of the business, called diabetes. Am I wrong?