Saturday, April 14, 2012

Three Months of New Studies

I decided to take a look at all the studies which were reported for the first time in the FDA's Clinical Trials site between January 1st and April 1st of this year.  Registration at this site is required for all studies done on people in the US, or that will be submitted for eventual FDA drug approval, and here I"m looking at all the new ones (not updates to existing ones) for a 3 month time period.  Here is a quick summary:

51 type-1 diabetes studies started, of which:
  2 Were testing new (non-insulin) treatments for type-1
  5 Artificial Pancreas studies
  2 Studies aimed at curing/delaying type-1 during the honeymoon phase.
(none were aimed a curing established type-1 diabetes)

Obviously, I'm going to discuss these nine, and especially the last two more below, but first, I want to give a very quick summary of the other 42 studies.  The largest group (14) were testing different types of insulin (Aspart 30 or 70, Degludec, Levemir, and so on). About 5 studies were aimed at complications, about 5 had psychological targets, 2 involved new ways of giving insulin, and 2 were new BG measuring techniques, 3 involved food or diet, and so on.

If I had to select the silliest study that started in the first quarter of 2012, it would be this one: "The Effect of Guided Imagery in Children With Type 1 Diabetes Mellitus on Glucose Levels and on Glycemic Control" (NCT01567254). Unfortunately, the clinical trial record doesn't say who is funding it.

New Clinical Trial of Proinsulin Peptide on Honeymooners

Proinsulin is made by beta cells, and it is later broken down into insulin and C-peptide.  These researchers hope that giving proinsulin to type-1 diabetics in their honeymoon phase will teach the immune system not to attack itself.  This is similar to how repeated injections of peanut antigens are used over time to stop allergic reactions to peanuts.  (Note that while this trial is on honeymooners, the peanut trick works on people who have been allergic to peanuts for a long time, so it is not clear to me that this general approach is limited to honeymooners.)

There have been several clinical trials aimed at giving insulin or closely related molecules to people at risk of diabetes or in the honeymoon phase to try to train the immune system not to attack the body's own beta cells.  So far, these have not cured or prevented, but a few "rays of hope" have been seen.   So the work is continuing as researchers refine their techniques and try variants that were not tried before.  This type of treatment would likely need to be combined with a beta cell regeneration technique to result in a cure for established type-1s, and maybe for honeymooners as well.

This study will run for 3 years, and will enroll 24 people.   Two groups of eight will get proinsulin at different doses, and one group of 8 will be the placebo group.  This is double blind, placebo controlled.

This trial is being done at Cardiff, Newcastle, and London in the UK, and is part of the research done by the Diabetes Vaccine Development Centre.

Clinical Trial Record:
Patient information:

New Clinical Trial of GABA on Honeymooners

GABA is sold as dietary supplement in the US, but this is the first trial I know of to test for type-1 diabetes in people.  It is being done by Dr. Lunsford at the University of Alabama at Birmingham.  They will measure C-peptides, A1Cs and change in insulin use over a 1 year period.  This study is double blind and placebo controled: A total of 30 people will be enrolled, 20 will get GABA and 10 will get the placebo.  To enroll,  patients must be within 12 weeks of diagnosis, although they haven't started to enroll quite yet.  The paper was filed in March, and said they planned to start in April.

Clinical Trial Record:

Some Discussion of GABA

One obvious question is, why does GABA work?  I'm not exactly sure.  GABA has been studied in relation to type-1 diabetes since at least 1990.  Some work suggests that it is a immunmodulator, so lowers the immune systems attack on the body's beta cells.  Other work suggests that it lowers inflammation, so if inflammation is a trigger of type-1 diabetes, then that is a mechanism for GABA be effective.  GABA and GAD are interrelated chemicals in the body, and GAD is the most common target of autoantibodies in type-1 diabetes, so there might be a mechanism there, as well.

This research provides a strong counter example to the idea that "generic drugs can't get funding for research" or "no one will work with cheap, available drugs, because there is no profit in it" or similar canards.  GABA is widely available "over the counter" (no prescription) right now.  It is not covered by a patient, and there are dozens of companies that sell it.  Yet these researchers are able to fund and run a clinical trial for it.   GABA was reported to have cured type-1 diabetes in mice in June 2011, so it looks like it will move from mice to people in a year, which is quick.  Most treatments take about 2 years to make that transition:

Artificial Pancreas Studies Starting in Q1 of 2012

I'm still trying to find a good way organize these, since there are so many.  My current thinking is to divide them by "stage"  (based on the JDRF's six stages of AP development), and then further divide them into commercial development and academic research, and then (finally) list them by research group.  So that is how they are described below.
Background blog posting:

Important note: I've tended to name the research groups after one researcher involved, but I'm not sure that is a good way to do it.  I'm sorry if these groups are named after the wrong person, and I know they are all partnerships, with many people working together, I just don't have a better way to name them right now.  The names below are not designed to slight the many other researchers involved in each project!

All of these studies are recruiting new participants.

Hovorka's Group in Cambridge, UK.  Stage 3 or 5. Academic Research
12 people total, runs from May 2012 to December 2012.  Open label (non-blind, no placebo).
This study is looking specifically at children 2-6 years old, and using deluded insulin to better support them, over a 2 day period.
Clinical Trial Record:

Group in Montreal, Canada.  Stage 4 / Stage 6.  Academic Research.
12 people total, starts in January 2012.  Open label, cross over design.
This study is using a dual-hormone AP and is comparing how well it works when the pump is told about means vs. when it needs to handle meals without being forewarned of them.
Clinical Trial Record:

Hovorka's Group in the UK.  Stage 3 or 5. Academic Research
20 people total, runs from August 2011 to August 2014.  Open Label.
This looks like a long term trial of an AP, lasting 18 months, rather than the 1-3 days as is common in other studies.
Clinical Trial Record:

Montpellier University Hospital, Montpellier, France
10 people total, runs from Feburary 2012 to March 2014. Open label.This study is testing insulin delivery which is Intraperitoneal (injected into the body) rather than just under the skin, which is normal, or into a vein, which has also been done.
Clinical Trial Record:

Dr Ward's group in Oregon, USA.  Stage 6 Academic Research
10 people total, runs from March 2012 to September 2012.  Open label.
Inpatient testing of dual hormone AP.  In previoius studies, these researchers used the same hardware but entered data by hand.  In this test, they are using a truly closed loop, without human intervention.
Clinical Trial Record:

New Treatments for Type-1

One of the studies was testing Sitagliptin as an additional (to insulin) therapy for type-1 diabetes.
This is a 30 person study which is recruiting now and is expected to finish in March 2015.  It is single blind, and is testing 3 different doses of the drug, and one placebo group.  This study is being done at the Albert Einstein College of Medicine in the Bronx, New York City, USA.
Clinical Trial Record:

The other was testing Liraglutide to see if it changes the glucagon response during low BG episodes.  (I'm not sure why this is important.)  This is a 42 person study which is recruiting now and is expected to finish in September 2012.  It is double blind, placebo controlled.  Three different groups which each get a different dose of Liraglutide for some time, and then placebo for some time.  This study is being done by Novo Nordisk in Graz, Austria.
Clinical Trial Record:
Portal to all Novo Nordisk clinical trials:

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.
Clinical Trials Blog:
Cured in Mice Blog:


Anonymous said...

Thank you for all of your research. I'm wondering if there has been any more information on work being done in Geneva with changing alpha cells to beta cells, that I read about over a year ago. Here is a link to a press release on it.

Joshua Levy said...

Anonymous at 15-April 2:01pm:

That research looks very interesting to me, but it is done in animals, not people, so I don't cover it here. The research funding is for "pre-clinical" work, meaning more work in animals. If they start any clinical trials (experiments in people) I'll cover it here.

Joshua Levy