Thursday, August 8, 2019

Personal Note

I've been very busy this summer, and so I only published one blog posting in May, one in June, and none in July or August.  I do plan to restart my normal publishing schedule in September, which means 2 or 3 postings per month.

Also, when I do post in September, I'll be removing the "In my day job, I work in software for Bigfoot Biomedical." since that is no longer true.  I wish them all the best success.

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, JDCA, or Bigfoot Biomedical news, views, policies or opinions. In my day job, I work in software for Bigfoot Biomedical. 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.

Tuesday, June 18, 2019

MER3101 Starts a Phase-I Clinical Trial

MER3101 is vaccine-like formulation of Insulin Beta Chain (IBC) and MAS-1, an adjuvant.   That makes more sense when you read it back to front, and go through it word by word:
  • An adjuvant is something that stimulates the immune system, so that the immune system reacts more strongly to a vaccine.  Think of it as a turbocharger for vaccines.
  • MAS-1 is a specific adjuvant which was developed by Nova Immunotherapeutics Ltd, and which they have already tested in another formulation (MER4101) targeting the flu.
  • Insulin B-Chain (IBC) is part of an insulin molecule.  Insulin is normally composed of an A-chain and a B-chain connected in two places.  
The idea behind this trial is to expose the immune system to part of the insulin molecule in order to train the immune system not to attack beta cells which generate that insulin.  This is vaguely similar to giving people with a peanut allergy peanut proteins in the hopes their body will learn to accept peanuts.  But remember that is a crude analogy, and type-1 diabetes is not a classic allergy!

We know that type-1 diabetes involves at least five different autoantibodies: islet cells (ICA), insulin (IAA), GADA, IA2 (also called ICA512), and ZnT8A.  Of these, the insulin autoantibody (IAA) often shows up first, so several researchers have tried to cure or prevent type-1 diabetes by teaching the immune system not to generate these autoantibodies.  This clinical trial is another in this line of research.

This study can be thought of as a follow on to this previous work:
https://cureresearch4type1diabetes.blogspot.com/2011/05/orbans-phase-i-results.html

This Study

The study design is more complex than usual.  It's clear they are trying to get as much out of this study as they can:
  • The study is divided into 4 groups.  Each group has 5 people getting the treatment, and 2 people serving as controls for that group.  
  • The first three groups will each test different doses of IBC, but the same dose of MAS-1.
  • The fourth group will test whichever IBC dose was most successful, but with a higher dose of MAS-1 that was previously used.
The primary results are safety and immune effect, which are important to running more studies in the future, and learning about the vaccine.  The secondary results are measuring success for both a cure and a treatment: C-peptide, A1c, and insulin use.

People in this study must be between 18 and 45 years old, and within 2 years of diagnosis.

The study started recruiting in August 2018, they hope to finish in April 2022, and was funded by the Helmsley Charitable Trust.

They are recruiting in one place:
    University of Colorado, Denver:  Aurora, Colorado, United States, 80045
    Contact: Mara Kinney    303-724-8272    mara.kinney@ucdenver.edu 
    Contact: Hali Broncucia    303-724-7526    hali.broncucia@ucdenver.edu 
    Principal Investigator: Peter Gottlieb, MD 

Clinical Trial Registry: https://clinicaltrials.gov/ct2/show/NCT03624062

The History

I usually don't discuss the corporate history of the treatments I cover, because all I really care about is the results of clinical trials, and it doesn't really matter what companies sold what technology to what other companies.  However, I'm describing the history here, because I think it shows the convoluted path that a lot of these smaller companies take in order to get their treatments to market.  And it helps explain why things take so long for less established companies.

Dr. Tihamer Orban has been working on curing / preventing type-1 diabetes using vaccines based on the Insulin B-Chain for at least 10 years.

The earliest human trials that I know of were done at the Joslin center and reported in 2010, on an IBC based formulation called IBC-VS01.  This is how I summarized the results back then:

In terms of safety, the results were fine: nothing bad happened, and this is a new treatment, so safety was an important question.  But in terms of effectiveness, the results are mixed.  The vaccine did result in a specific immune system change that looks promising. ... But no effectiveness was seen during the trial.  Their was no improvement in C-peptide generation of the treated group compared to the non-treated group.
You can read more in my previous post:
https://cureresearch4type1diabetes.blogspot.com/2011/05/orbans-phase-i-results.html

After this trial, Dr. Orban created his own company Orban Biotech to pursue this research which was issued patents in the 2012 to 2014 time frame, but is not operating now.

On the adjuvant side, a company called Mercia licenced an adjuvant technology from another company called Aphton and developed it into MAS-1.  They then started a group of research projects, collectively called MERIT, to combine MAS-1 with different vaccine parts (called "antigens") to create vaccine-like treatments for four different diseases (Type-1 Diabetes, Influenza, Alzheimer's, and Asthma).

The type-1 diabetes branch of this research was to work with Dr. Orban to combine his IBC-VS01 antigen with their MAS-1 adjuvant to create MER3101 which Mercia is now testing.  In order to show the history of MER3101, the Mercia web page shows some of Dr. Orban's previous IBC-VS01 results, renaming it MER3001.  In the world of fictional fandoms, this would be called retroactive continuity ("retconning" for short) to make it look like Mercia has been involved since before 2010.

Some Discussion
  • While I think 28 people in a phase-I trial is a solid number, in this case, they are divided into four groups.  Each group is 7 people, 5 people are actually getting the treatment and 2 are controls for that group.  Each group is pretty small, even for a phase-I trial.  My gut feeling is that if they see a small effect in only one group, that likely is a mistake.  However, if they see a reasonable effect in more than one group, that signals they are on the right track.
  • I don't think it is a good idea to recruit people within 2 years of diagnosis, because I view those people as two very different subgroups.  Some will be in their honeymoon phase, and therefore generating some of their own insulin from their own beta cells, while others will be passed that, and have almost no natural insulin generation.   I think mixing them in one study is dangerous, especially where each group only has 2 in the control group, and 5 in the treatment group.  I'm specifically worried that if both control members come from one subgroup, while the treatment group is split between both subgroups, that could cause differences that are not real.

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, JDCA, or Bigfoot Biomedical news, views, policies or opinions. In my day job, I work in software for Bigfoot Biomedical. 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.

Wednesday, May 1, 2019

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

This blog posting contains two different new items, with a short note on each:

The One That Got Away

The first article covers some work in Multiple Sclerosis (another autoimmune disease):
https://www.painnewsnetwork.org/stories/2019/1/16/experimental-stem-cell-therapy-reverses-ms-in-some-patients
The article reports on a promising phase-II study on an incurable disease.

The reason I'm discussing it here, is because this researcher was involved in very similar clinical trials on people with type-1 diabetes, many years ago.  Those trials were the most successful ever done.  People did not use injected insulin for years.  You can read my previous blogging here:
https://cureresearch4type1diabetes.blogspot.com/2010/11/snarski-confirms-burts-phase-i-results.html
or more generally here:
https://cureresearch4type1diabetes.blogspot.com/search/label/Burt

But years ago, this researcher switched from Type-1 Diabetes to Multiple Sclerosis.  Why?  Because of safety trade offs.  One researcher told me that the T1D version of this treatment would likely have an expected death rate of 1%.  In actual studies (on people!) the death rate was about 1 in 65.  For a disease like Type-1, that is not acceptable.  But for a disease like Multiple Sclerosis (which can lead to death after 10-30 years, and which often has a much bigger quality-of-life impact), maybe it is acceptable.

So, while I'm sad that the type-1 world will not benefit from this research (at least not in the short term), I am happy that our disease is not so dire that a treatment like this is viable.

Phase-II T-Rex Trial Reports Unsuccessful Primary Results

On a completely different note, the T-Rex Trial reported its primary end point.  For background,
you can read my previous blogging about this research here:
https://cureresearch4type1diabetes.blogspot.com/search/label/Polyclonal%20Tregs

A quick summary of this treatment is as follows: remove one specific type of T regulator cell (called "CD4(+)CD25(+)CD127(lo)") from a person with type-1 diabetes.  Grow them out so you have about 500 times more, and then put them back in the same person.  Since regulatory T cells naturally regulate the body's immune system, and the patient now has more of them, the hope is that they will prevent the autoimmune attack which causes type-1 diabetes.

In February, the T-Rex trial reported its primary end point results at 1 year, and they were unsuccessful.  The exact quote was:
no improvement in the primary endpoint of preservation of C-peptide levels vs. placebo at 1 year was observed at the group level (using the standard mixed meal tolerance test)
Of course, the company is hopeful that they can find some good news by reanalyzing the data, looking at subgroups, etc.  but I'm very dubious about this.  In the type-1 diabetes research that I follow, I have yet to see this kind of reanalysis yield a success after the primary analysis was unsuccessful.  The trial is scheduled to collect data for two years, so there should be another update in about a year.

This information all comes from a corporate press release.  There was no mention of a research paper.

Press Release: https://www.caladrius.com/press-release/caladrius-biosciences-reports-top-line-data-for-the-phase-2a-sanford-project-t-rex-trial-of-clbs03-for-recent-onset-type-1-diabetes/
News coverage: http://www.evaluate.com/vantage/articles/interviews/caladrius-refuses-give-tregs-diabetes

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, JDCA, or Bigfoot Biomedical news, views, policies or opinions. In my day job, I work in software for Bigfoot Biomedical. 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.

Wednesday, April 17, 2019

Can A Rotavirus Vaccine Prevent Type 1 Diabetes In Some People?

In this blog posting I'm discussion an observational study, that is, a study where different groups of people are observed to see if their differences cause more or less disease.  This is quite different than the intervention studies that I usually cover.  Intervention studies are much better controlled and their results are more likely to be supported by future research.   However, I though this study was interesting enough to discuss even as an observational study.

This is the Reuters headline:
Rotavirus vaccination tied to lower rates of type 1 diabetes

For comparison, this is the headline from The Scientist:
"Results from an observational study find that the introduction of a routine vaccine in Australia coincided with a fall in the incidence of the autoimmune condition."

So what data did they look at, and what did they see?

They looked at people diagnosed with type-1 diabetes in Australia, and compared the 8 years before 2007 to the 8 years afterwards.  That was the year the Rotavirus vaccine was universally introduced to Australia.  This analysis covered about 16,000 children who were diagnosed with T1D.  What they saw was that the number had been stable up until 2007, at 8.7 per 100,000 kids [d1].  However, after they started giving the vaccine to all babies, the rate dropped to 7.8 per 100,000, a drop of 14%.
Graph is from the published paper, and is presented
 for educational purposes only.


Discussion

Rotavirus or 2007?
For me the big, obvious question is: did the type-1 diabetes rate drop because of the Rotavirus vaccine or because of something else that happened in 2007?  In a sense, this is the only question that really matters.  If you only look at this study, there is no way to tell.  However, this research group has been studying the connection between Rotavirus and T1D for many years, and they do think the two are related, and it's not just some random 2007 thing.

I did a very quick literature search, and found several studies (including some done previously by this group), which showed a connection between rotavirus infection and type-1 diabetes.  There were also some computer simulation studies, and some "mechanistic" studies (showing how a Rotavirus infection might cause or speed up the development of type-1 diabetes).  So the idea that the two are linked is not far-fetched.

Just One Study? / What about other research?
Another question is: Are there other studies showing that a Rotavirus vaccine might lower type-1 rates?  Or, is this the only one? 

In my literature search,  I only found one similar study done in people.  The researchers compared type-1 diabetes rates in children who had been vaccinated against Rotavirus to children who had not (all born in the same year).  Rotavirus vaccination did not lower type-1 rates in this study [d3], and that is not promising.

I very much hope that these researchers perform similar analysis in other countries which introduced universal Rotavirus vaccination.  If they see that county X introduced the vaccine in 2010, and saw a drop in type-1 in 2010, that does two things at once: it confirms this study, and it suggests that the vaccine is important, rather than the year.

Does Prevention Matter? / Does 14% Matter?
I know many people touched by type-1 diabetes don't care about prevention.  And I understand that; after all, in a sense prevention is too late for them.  But I will continue to care about prevention, even though it will not help my daughter.  First, because I think we might learn something from a prevention that might lead to a cure in the future.  That is not always true, of course, but it certainly is possible.  Second, because someday my daughter may have kids of her own, and a prevention for my grandchildren would be worth a lot to me.  Third, just in general, I want the world to be a better place even if my family doesn't personally benefit.  And prevention will surely help many people in the future.  (Of course, there is a counter argument: that prevention will cause research money aimed at a cure to "dry up", because there will be less and less need of it in the future.)

Finally, some people will belittle the 14% drop.  They will point out, that's not a lot, and many people will still get type-1.  That is true, but for me, it's besides the point.  Right now, we have nothing that lowers the chance of type-1 diabetes after a person is born [d2].  So going from nothing to one thing, and going from 0% to 14% are both big improvements.  I don't think we should let the perfect become the enemy of the good when it comes to solutions.  A drop of 14% (if confirmed by future research) is an important first step.

More Reading
Details

[d1] I assume those numbers are just for people diagnosed between 0 and 4 years old.  They are much too small to be everyone diagnosed with type-1 diabetes.  Total type-1 rates in the US are generally between 1 in 250 and 1 in 500.

[d2] Universal Rubella (German Measles) vaccination is thought to lower the rate of type-1 diagnosis in the population (but no where near 14%).  However, it is generally believed that this is caused by preventing measles in pregnant women since contracting Rubella during pregnancy significantly raises the chance that the child will (eventually) be diagnosed with type-1.  So this is a pre-birth intervention.
https://www.diapedia.org/type-1-diabetes-mellitus/2104282116/the-congenital-rubella-syndrome-and-diabetes

[d3] The exact quote was: "The adjusted relative risks (with 95% confidence intervals) were 0.91 (0.69-1.20) for T1D ... in vaccinated children compared with unvaccinated, suggesting that oral rotavirus vaccination does not alter the risk ... T1D during 4-6 years follow-up after vaccination."
This study covered 500 children.
https://www.ncbi.nlm.nih.gov/pubmed/28399059

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, JDCA, or Bigfoot Biomedical news, views, policies or opinions. In my day job, I work in software for Bigfoot Biomedical. 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.

Friday, March 29, 2019

My Theranos Story


I'm listening to the book "Bad Blood" by Carreyrou.  It is a fun read, and I think it is very valuable for me.  I'm a big cheerleader of Silicon Valley; a strong proponent of the risk-taking culture found here.  And I also follow a lot of medical research (obviously).  Therefore it is even more important for me to be reminded of the weaknesses both of Silicon Valley specifically and medical research in general.  This book is all about those weaknesses.

My Theranos Story

I'm on a mailing list of parents of kids who have type-1 diabetes.  It is a great resource, and I recommend everyone connected to type-1 diabetes join some sort of support and information sharing group.  In Dec 2013 there was a posting about a Silicon Valley blood testing start up called Theranos, that was going to make cheap, quick blood tests available which used only a few drops of blood.  Their first site was a Walgreens in Palo Alto.  They had a price list online (as I remember) and C-peptide tests were just a couple of bucks.  Less than the cost of a sandwich.  I had this idea to invite a bunch of parents and children from the email group to meet at the Walgreens one weekend morning.  We could all get tested, get the results, and maybe afterwards go out for ice cream later and talk about type-1 diabetes.  Since the parents would mostly have normal C-peptide numbers, and the kids (with type-1) would have nearly zero C-peptide numbers, it would immediately be obvious if the test worked or not.

However, based on many years of blogging about research, before I suggested this to the group, I figured I'd look up the research on their new testing machine.  So I did some of my standard queries on Pubmed (a US government database of publications), and scholar.google.com (Google's big research database), and clinicaltrials.gov (the FDA's clinical trials registry), and a few other places.  Nothing.  Not one paper.  I was really shocked.  Normally, you can't sell a treatment until it has gone through at least four human trials, so I was really surprised that I could find nothing for this new testing system.  (I did not know at the time that tests were regulated by a completely different US government agency, and in a completely different way, than treatments.)

Anyway, desperate for information, I looked online for the company's organization and basic balance sheet.  At that time, I had worked for Silicon Valley start ups for over 20 years, and I knew how to read a balance sheet, and how stock worked.  But there was none of that.  The only information that I found was Theranos's board of directors.  My years of working for start ups had given me experience with many different boards of directors, so I knew what to expect.  Or I thought I did.

The first name was George Schultz.  A guy famous for lying, and for being a Secretary of State (ie. foreign relations).  The next name I noticed was Henry Kissinger.  Another guy famous for lying, and foreign affairs.  [Note: I'm telling this story from my point of view.  I realize that other people may consider these two famous for other things.]  There was some long time senator (Sam Nunn, I think), and a big time general (Mattis?).  I was flabbergasted.  Why were these guys on the board of directors for a medical device company?  Where was the medical expertise?  Where were the expert venture capitalists (VCs) who funded medical devices?  Where were the people who had actually run a company before?  It was like a Saturday Night Live skit.

I thought about this for a while.  Should I judge a company based on its board of directors?  Maybe there was some reason all these guys were there.  Shouldn't I be deferential to all these famous, important people?  Maybe I could imagine some good reason for this.  But then I caught myself.  The only reason I was even looking at their board of directors was because there was no actual/published clinical trials showing the testing system worked.  There is no excuse for that.  If a treatment for type-1 diabetes had zero clinical trials, I would ignore it.  Well, I would wait until they started a clinical trial, and then evaluate it based on the results.  I should have the same standard for testing companies;  I would not evaluate their board of directors.

So I dropped the idea of getting a crew together to get tested by Theranos.  I decided to wait until they published results showing their tests worked.  They never did.  Years later Carreyrou published a series of newspaper articles describing what a fraudulent house of cards it was.

Learning From Theranos

After reading the book, and reflecting on my own experience with Theranos, a question popped into my head: why was it that in a couple of hours on a weekend morning, with no special insider data, and making a minor decision about how to spend a morning, I decided Theranos was not worth even a little time.  Compared to the venture capitalists (VCs) who spent weeks researching Theranos, could ask for insider information, had direct contact with the CEO/founder of the company, and were making million dollar decisions, and yet they decided Theranos was worth it.

Was I just lucky? Maybe.  But I do think I was helped by two things: (1) when I was making the decision, and (2) that I did not have direct contact with Theranos.

When Decisions Get Made
I had a big advantage over most of the investors, in that I was making my decision relatively late in the game, and therefore it was completely reasonable for me to expect public results.  When those were not available, I realized there was a problem.  Most of the investors made their decisions much earlier in the process, when less data was expected to be available.  Therefore, the lack of data did not make them suspicious.  How do we avoid that problem?   In two ways:

First, be willing to delay your judgement on new research.  The VCs wanted to invest early because they would make more money that way.  We need to invest early to nurture early stage research, but we don't need to decide that one particular line of research is going to be the cure.  That decision, the decision to emotionally commit to the research (to be a cheerleader), we can hold off on.  And we should.  If you think something might be the cure, you can always donate some money initially, but wait a few years, and check on their progress, to see if it really is the cure.  (Type 1 is forever, so waiting a few years is reasonable.)

Second, be willing to change your mind as the situation changes.  Most people have a hard time changing their minds, and this was on display during the whole Theranos saga.  Several VCs who had decided the company was going to revolutionize testing in 2006 still believed it in 2016, by which time they should have known better.  A good scientist changes their mind when new data is available, but that is the easier part.  The harder part is to change your mind when no new data is available, but forward progress should have resulted in new data, but hasn't.  The hard part is to realize when no new data is (in fact) bad data.

Answer The Right Question
The right question is: what is the data available that shows this is working (compared to the data that should be available).  The answer to that question was obvious when I did my web searches.  However, the questions that most of the investors were asking were different: Is what Elizabeth Holmes says is going to happen, really going to happen?  Is she going to revolutionize blood testing?  Is she telling the truth?  Those questions are much harder to answer, much more emotional, much more personal, than the question that I tried to answer.

Asking the right questions is harder than it sounds.  Humans have been making decisions about people and trustworthiness for over 100,000 years.  Our brains are hardwired to do that, because we lived and worked in small groups who knew each other well.  We worked with them every day and for our whole lives.  The scientific method has existed for only a few 100 years.  It is not the go-to method our brain naturally uses.  But the world has changed so that we are now making decisions about people who we fundamentally do not know, not in the way our brains evolved.

I do think that every one of us, when presented with new research, can ask the right question.  The moment we even start to think about "is this person right" or "are they trustworthy" or "are they going to change the world", to just immediately de-personalize the question: do they have the data that they should have at this point in the research?  Ignore excuses; ask about data.

Finally

These are a little off the beaten path, but well worth a read:
https://mondaynote.com/theranos-could-have-been-stopped-9670793e3431
https://www.stanforddaily.com/2019/01/15/theranos-whistleblowers-reflect-on-failure-of-the-silicon-valley-unicorn/
https://www.entrepreneur.com/article/311036
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3275363/
(On March 16 I asked for this paper to be retracted. We'll see how that goes.)

A reminder of how this fraud was presented in the news prior to the "Bad Blood" reporting:
https://www.wired.com/2014/02/elizabeth-holmes-theranos/
http://fortune.com/2014/06/12/theranos-blood-holmes/



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, JDCA, or Bigfoot Biomedical news, views, policies or opinions. In my day job, I work in software for Bigfoot Biomedical. 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.

Saturday, March 23, 2019

Azithromycin Starts A Phase-II? Clinical Trial (AIDIT)

Azithromycin is an antibiotic which has been available since 1988, and is widely prescribed, with a good safety record.  Antibiotics are effective in curing bacterial diseases, but not viral diseases.  This trial is the first I've covered where an antibiotic was tested to treat, prevent, or cure type-1 diabetes, so it represents a new treatment path.

Why Azithromycin?

There are several different theories about what causes type-1 diabetes, one of which is that bacteria moving from the duodenum to the pancreatic duct causes type-1 diabetes.  The duodenum is the part of the small intestine closest to the stomach.  This is one of the "stomach flora" or "gut bacteria" theories which have been in the news recently.

If the cause is bad bacteria in the pancreatic duct, then (these researchers theorize), maybe the cure is to give the patient a dose of antibiotics to kill the bacteria, extra insulin to lower the stress on the remaining beta cells, and dietary guidance to prevent excess bacteria from moving from the duodenum to the pancreatic duct in the future.  All this would be done very quickly after diagnoses of type-1 diabetes.  That is the quick summary of the rationale behind this clinical trial.

This Clinical Trial

This trial is called the "Azithromycin Insulin Diet Intervention Trial in Type 1 Diabetes (AIDIT)" to include all three of the interventions being used.  This trial will enroll people between 6 and 16 years old, who have been diagnosed within the last 10 days, so only "just diagnosed" people can participate. 

The plan is to recruit 60 people, half of whom will get the treatment, and half will not.  The study is not blinded.  It started in Sept-2018 and they expect to finish in Dec-2021.

People will get three doses of Azithromycin per week, which is based on a protocol which has been used for years to treat people with cystic fibrosis.  On a monthly basis, they will be given extra insulin via an IV, which is designed to give beta cells a rest and help them regrow.  Finally, they will also be given dietary advice designed to have them drink less at meals, and eat meals more slowly, which is designed to prevent bacterial migration.

The study will run for a year, with C-peptide numbers being the primary end point.  There are a total of 21 different secondary end points, including time within BG range, A1c, several measures of diet, quality of life, etc.

They are recruiting at one site in Sweden:
The Queen Silvia Children's Hospital / Sahlgrenska University Hospital, Gothenburg, Sweden
Contact: Gun Forsander   
Contact: Olle Korsgren, MD, PhD +46176114187 olle.korsgren@igp.uu.se

Funding is from Barndiabetesfondens (Child Diabetes Foundation) in Sweden.

US Clincial Trial Record: https://clinicaltrials.gov/ct2/show/NCT03682640
EU Clinical Trial Record: https://www.clinicaltrialsregister.eu/ctr-search/trial/2018-002191-41/SE
Wikipedia: https://en.wikipedia.org/wiki/Azithromycin

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, JDCA, or Bigfoot Biomedical news, views, policies or opinions. In my day job, I work in software for Bigfoot Biomedical. 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.

Tuesday, February 5, 2019

How to find a clinical Trial (2019 Update)

The decision to join a clinical trial is a personal one, which I believe is best made between the person with type-1 diabetes (or parents) and their doctor.  However, I know that some type-1s don't have regular endocrinologists, and also some doctors don't tell their patients about available trials.  Therefore, I've put together this blog on how to find clinical trials, so that people with type-1 diabetes, who want to, can find trials to discuss with their medical team.

The web pages discussed below have a wide range of goals, so you will find trials aimed at curing, preventing, and treating type-1 diabetes, and also the complications caused by type-1 diabetes.  These trials also include many different methods: new drugs, new devices, diets, psychological treatments, surgeries, etc.

If you know of any web site useful to finding T1D studies, which is not on this list: please send it to me, so I can add it!

Web Sites That Search For Clinical Trials

JDRF has a good web page to find clinical trails based on age and location: https://www.jdrf.org/research/clinical-trials/
(This tool finds all type-1 diabetes studies, not just those funded by JDRF.)

There is also a blog created by Jennifer Schneider which has a great map to help you find type-1 clinical trials: https://type1trials.blogspot.com/ 
The map by itself is here:
https://www.google.com/maps/d/viewer?mid=1OL5RWPz-D1FiViGpxhAjqEEv2Q2Ck_n3&ll=45.137952951318496%2C-102.69609393571398&z=5

Using This Blog

When I blog about a new clinical trial, I usually link to their recruitment page, and include the names, emails, and phone numbers of the recruiters.  This information is usually with the first posting announcing that they have started recruiting.  I also include a link to the Clinical Trial Registry (often an "NCT" or "ISRCTN" number.  By following this link, you can often find even more information on the trial.  So you can search through this blog to find interesting clinical trials near you.

Other Organizations To Search

If you want to do more searching on your own, then you can check out the following web sites:

https://www.immunetolerance.org/patients/autoimmune-disease
The Immune Tolerance Network (ITN) is a very interesting organization, which I view as part of the "infrastructure" of diabetes research.  They help researchers organize and run clinical trials aimed at stopping autoimmune attack, and similar subjects within the immune system.  They cover research into type-1 diabetes, and also related autoimmune diseases.  At any one time, they usually have a dozen or so studies going on, and a couple are recruiting all the time.

Because ITN runs a network of doctors who cooperate in clinical trials, their trials often recruit at many different sites all over the US (and sometimes the world), so you have more chances to enroll.  Their studies are more likely to be available near you.

The ITN's Home Page: https://www.immunetolerance.org/

Official Clinical Trial Registries

All clinical trials should be registered at some official web site, so these are the largest and most diverse places to look for a study.  In general they contain a lot of information, but are clunky to use. They are more designed for research professionals, than random people looking for a trial.

You can search for phrases like "type-1" and "diabetes" and limit your search to studies that are recruiting right now, and even by location where they are recruiting.   Personally, I've found the JDRF site has the same information and is much easier for a patient or parent to use.  But the FDA site has more info, so if you find a trial using the JDRF site, you can look up the same trial on this site, and learn more about it.

http://www.clinicaltrials.gov
This is the official US FDA registration site for clinical trials.  It covers just about everything in the US, and many trials not done in the US are registered here as well.

http://www.who.int/trialsearch/
This is the United Nations's official registration site for clinical trials which covers the whole world.  Searching here will find trials registered in individual country's registry databases (all the sites listed in this section, plus many more).

https://www.clinicaltrialsregister.eu/ctr-search/search
This is the European Union's official registration site.

http://www.anzctr.org.au/BasicSearch.aspx
Australia and New Zealand

https://upload.umin.ac.jp/cgi-open-bin/ctr_e/index.cgi
Japan's clinical trial registry (in English).

Note: China has a clinical trial registry in English as well, but I could not get it to work:
http://chictr.org.cn/enIndex.aspx

Looking Near You

If you are near a major university or diabetes research center, you might want to "reach out" to them.  I know that UC San Francisco, Stanford, The Barbara Davis center at University of Denver, DRI (in Miami), University of Florida at Gainsville, the Joslin center and Harvard (both in Boston) are all doing multiple studies.

Google can help you find the recruiting web pages for these studies, by searching for the name of the University and following it with "endocrinology clinical trials".

Everyone Is Near The Web

Finally, If you are more a "do it yourself" person you might want to look at the Facebook group "Prevent Autoimmune Disorders".
https://www.facebook.com/groups/preventautoimmunedisorders/
This group is crowd sourcing a test of Vitamin-D and Fish Oils as a preventative.  You can read the information in this group, and decide weather or not to participate.

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, JDCA, or Bigfoot Biomedical news, views, policies or opinions. In my day job, I work in software for Bigfoot Biomedical. 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.