Two New Clinical Trials (HCQ and Baby Teeth Stem Cells)

Hydroxychloroquine to Prevent Type 1 Diabetes

Hydroxychloroquine (HCQ) has been in the news recently because of claims that it may treat/cure COVID-19.  However, for this blog, I thought I'd update people on the clinical trials that are testing Hydroxychloroquine as a prevention of T1D.  (Note that HCQ has some T2D applications, which I'm not discussing here.)

Hydroxychloroquine is approved in the US for treatment and prevention of Malaria and some autoimmune diseases, such as Lupus and Rheumatoid Arthritis.  There are two reasons to think it might help with type-1 diabetes.  First, it helps with other autoimmune diseases.  Second, it is an anti-inflammatory and inflammation is seen in the pancreas of people with type-1 diabetes.

A large HCQ  trial started in Aug-2018 and is expected to run until Aug-2024.  The goal is to enroll 201 people who have tested positive for two autoimmune antibodies, but have not shown any symptoms of T1D.  During the study, people will take a pill, either HCQ or a placebo.  They will be followed for years to see how many are diagnosed with type-1 diabetes.  It is being run by the Type 1 Diabetes TrialNet, led by Carla Greenbaum, and JDRF is helping to fund it.

The study is double blinded, so publishing any information prior to completion in 2024 would be very difficult, and (to the best of my knowledge) no interim results have been published.

The study is recruiting people at 40 different sites all over the US.  You can read more about the study here:

https://www.trialnet.org/our-research/prevention-studies/hydroxychloroquine-hcq

the list of recruiting locations is in the Clinical Trial Registry:

https://www.clinicaltrials.gov/ct2/show/NCT03428945

to see the limitations due to COVID-19 read this:

https://www.trialnet.org/events-news/coronavirus

Personal note: I know there is a lot of interest in HCQ as a COVID-19 treatment.  I have not been systematically tracking every study done in that area.  However, I can boil down what I have seen into six bullet items:

1. In order to get a drug approved for use in the US, in normal times, there must be three high quality studies done which show safety and effectiveness (one phase-II study and two phase-III studies).
2. Right now, there are zero high quality studies showing HCQ's impact on COVID-19.  Zero.  And that covers trials which were successful and trials which were unsuccessful.  Every trial I've seen reported, in both the scientific literature and the popular press, has been low quality.  By low quality I mean either no control group, no randomization, or it is not an intervention study at all:  very basic stuff.  I'm not quibbling about size, protocol, or even publication.
   
3. There have been several low quality studies done on HCQ and COVID-19.  These studies show approximately a 1 to 2 to 1 ratio of good to bad to neutral outcomes.  So for each 4 low quality studies done, 1 has shown success (improved outcomes), 2 have shown failure (meaning higher death rates or other bad effects), and 1 has shown no difference.
4. Because high quality research is slower and more expensive than low quality research, under normal circumstances I would never expect anyone to fund a high quality clinical trial based on the terrible results of the low quality studies done so far.  However, these are not normal circumstances, so there might be a high quality study done.  If one is done, those results will carry more weight than the stuff published so far. 
   
5. Because of how clinical trials work, low quality research is far more likely to be positive than high quality research.  If you are getting unsuccessful results 3 out of 4 times with low quality results, you're not going to get successful results in higher quality studies.  That's just not the way it works.
   
6. The last gasp of the true believers in a situation like this is to point at the large number of unsuccessful results, and say that they are all low quality results.  (The same is true of the small number of successful results as well, but they will not dwell on that.)  Therefore the idea is not disproven, because a high quality result would carry the day, if it were done.  Notice the switch where they are requiring mainstream science to prove their idea wrong, rather than the scientific method where new ideas must be proven correct by the proponents.  However, in real life, no one will ever do the high quality study, because the low quality studies are failing.  The true believers will blame a conspiracy, and the matter will die. 
   

Stem Cells From Baby Teeth Starts A Phase-I Study

This study is of personal interest to me.  My daughter was diagnosed when she was 18 months old.  When she started loosing her baby teeth it was known that each one contained a tiny amount of adult stem cells and there were companies that could freeze the teeth for later use.  At the time, little was known about how to get adult stem cells or what they could do.  But since our daughter already had T1D it seemed like something worth doing.  So we had some of her teeth preserved.   However, a few years later, there were many more known sources of adult stem cells, and the uses of adult stem cells were better known and T1D had not shown any successes with these kinds of adult stem cells.  So we stopped paying our storage fees.

Now, many years later, this is the first clinical trial I have seen that attempts to use the adult stem cells in baby teeth.

This study started in January 2019 and is expected to finish in December 2020.  It enrolled 24 people who had either T1D or T2D.  There is no control group.  Each person will get three injections of stem cells from baby teeth and then be followed for a year.  Primary outcomes are insulin usage and C-peptides (which measures how much insulin the person is creating naturally).  Secondary outcomes include A1c, blood sugar numbers, and proinsulin generation (another measure of how much insulin the person is creating naturally).

Clinical Trial Registry: https://www.clinicaltrials.gov/ct2/show/NCT03912480

The clinical trial record contains this note, and I've never seen anything like it before: "Note: at 1 month follow-up (V5) after the last transplantation of several cells, the subjects were still unable to discontinue insulin, and then began the second course of stem cell therapy. After the second course of treatment, the follow-up plan was resumed."

My interpretation of this is that the study is fully enrolled, and that (so far) no one has been cured.  This comment seems to imply that the researchers thought they might see some outright cures in the study, and these seems very optimistic to me.

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.