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

Here are some "bits and pieces" updates for December.

Update on Dr. Faustman's Phase-II Trial of BCG

Dr. Faustman's lab has published their Fall 2017 newsletter, which you can read here:
http://www.faustmanlab.org/docs/newsletters/DrFaustmanUpdateFall2017.pdf
This newsletter includes more information on her research, especially from the 3rd International BCG conference, The BCG Working Group, and the 2nd edition of the BCG and Autoimmunity book she edited.

There are three pieces of new news there:

1. The phase-II trial was fully enrolled in Summer of 2017. This is important because we now  know when the trial will end.  Since this is a five year study, they should finish collecting data in Summer of 2022 and publish before Summer of 2023. 
2. They have given BCG to the three untreated patients from their phase-I trial, so they will have data from six people to report in the future. 
3. The lab is going to be recruiting for more studies in the future, so would like to hear from anyone who is interested in participating.  No details on future trials were provided.

Another piece of news is that Dr. Faustman is branching out, and trying to apply BCG treatment to Fibromyalgia.  This research is being done in collaboration with EpicGenetics, and they hope to start the trial in early 2018.  If anything applicable to the type-1 world comes up in this research, I'll report it.  Since Fibromyalgia is not generally considered an autoimmune disease, I'm not sure how much "cross pollination" of results there will be.  You can read more about it here:
http://www.prohealth.com/library/showarticle.cfm?libid=30644
http://www.businesswire.com/news/home/20170419005324/en/EpicGenetics-Assistance-Leading-Medical-Centers-Expands-Clinical

DILfrequency Trial Completed

There is a lot of research ongoing on IL-2 which is part of the immune system.  About 18 months ago, I summarized all this research here:
http://cureresearch4type1diabetes.blogspot.com/2016/05/general-update-on-il-2-research.html
with an update here:
http://cureresearch4type1diabetes.blogspot.com/2017/01/possible-cures-for-type-1-in-news.html

One of those clinical trials was called "DILfrequency" and that trial has finished, and the results published.  The purpose of that trial was to develop the best dosing method of IL-2 which could then be used in future trials.  ("Best" in this case, meant a stable and known change in the immune system, which the researchers wanted.)  It was successful in terms of telling the researchers what they wanted to know to prepare for future clinical studies.

There are several IL-2 research projects either ongoing or planned to start (including by this group), so I think we'll get a stronger signal in the next few years.

Journal Article: https://www.biorxiv.org/content/early/2017/11/28/223958

Clinical Trial Record: https://clinicaltrials.gov/ct2/show/NCT02265809

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.

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

Catching Up With NNC0114­-0006 (Anti IL-21)

Back in 2015 Novo-Norsk started a clinical trial into a combo treatment of NNC0114-0006 and Liraglutide (which is more commonly known as Victoza).  I ignored this trial, because I thought that NNC0114-0006 was a new form of insulin, and they were testing a treatment for type-1 diabetes. However, I have since found out that NNC0114-0006 targets IL-21 and that Liraglutide may stimulate beta cell growth.  Therefore, this combination could have the effect of stopping the autoimmune attack while at the same time regrowing beta cells, and that would be a path to a cure.

Liraglutide is approved for use in type-2 diabetes and works by increasing insulin production. Recently, experiments in mice have suggested that it works (at least partly) by helping the body grow more beta cells, and preventing the death of beta cells:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4418765/

NNC0114-0006 is an anti IL-21 treatment.  IL-21 is a chemical that the immune system uses for communication, and several experiments have suggested that too much IL-21 is important to creating type-1 diabetes:
https://www.ncbi.nlm.nih.gov/pubmed/18779574
https://www.ncbi.nlm.nih.gov/pubmed/19208913
https://link.springer.com/article/10.1007/s00125-015-3509-8
(and there are many more such studies.)

So combining these two treatments provides a possible path to a cure.

The Current Study

The study that started in 2015 is a phase-II? trial (the question mark means that it is a phase-II trial, but there has never been a phase-I trial for this combination of treatments).  The basic study design is four groups: one group gets both treatments, one group gets two placebos, one group gets NNC0114-0006 and placebo, and one group gets Liraglutide and a placebo.  So they have all their bases covered. The study is large: 304 people recruited from 100+ sites all over the US and Europe.

The clinical trial record says that this study is recruiting patients.  However, when I look at the list of locations, every one is marked "Active, not recruiting", "Completed", or "Suspended", so I'm very hopeful that they have recruited all the patients that they need.  That is important, because they expect to collect data for 80 weeks.  Their target completion date is April 2019.

This is actually the fifth study of NNC0114­-0006.  You can see the list here:
https://www.clinicaltrials.gov/ct2/results?cond=&term=NNC0114%C2%AD-0006
The four previous studies were smaller (between 10 and 65 people), and were done on other autoimmune diseases: Rheumatoid Arthritis, Crohn's Disease, and Systemic Lupus Erythematosus.

Clinical Trial Registry: https://www.clinicaltrials.gov/ct2/show/NCT02443155
Other Study ID Numbers: NN9828-4150
2014-001215-39 ( EudraCT Number )
U1111-1154-7172 ( Other Identifier: WHO )
REec-2015-1768 ( Registry Identifier: Spanish registry )

Metreleptin Fails A Phase-I Trial

Back in the 2008-2010 timeframe there was some hope that Leptin would cure type-1 diabetes, and a clinical trial was started in 2010.  Then in 2015 the trial was canceled by one of the sponsors.  Finally, now in 2017 the results have been published, and the conclusions are:

Metreleptin is safe but may not be efficacious in improving glycemic control in patients with T1DM, although it reduces body weight and daily insulin dose modestly.

You can read my previous blogging here:
http://cureresearch4type1diabetes.blogspot.com/search/label/Leptin
The abstract is here: http://care.diabetesjournals.org/content/40/5/694?etoc
Clinical Trial Record: http://www.clinicaltrials.gov/ct2/show/NCT01268644

Interesting Treatment for Multiple Sclerosis

I usually do not blog on cures or treatments for other diseases.  However, MS, type-1 diabetes and several other diseases are all from the same family of "autoimmune diseases".  They are all caused by the body's immune system attacking a different organ or internal system.  So in theory, research into curing one of these diseases might help cure the others.

So with that in mind, I thought this study was interesting:
Multiple Sclerosis Therapy NKTR-358 Begins Phase 1 Clinical Trial:

Basically, this company has a treatment which causes a person to generate more Treg cells.  Since Treg cells regulate the immune system, having more of them might prevent the immune system from attacking the wrong cells.  In type-1 diabetes, we have several research programs aimed at increasing Treg counts, but usually by growing more Tregs outside the body, and then infusing them into the body (T-Rex, Stem Cell Educator, and Stem Cells of Arabia are all working on similar ideas). NKTR-358 is a treatment which (they hope) will cause the body to generate more Treg cells, itself.

Also, NKTR-358 works at least partially, by targeting the IL-2 receptor in the immune system, and this receptor is also an active target of research in type-1:
http://cureresearch4type1diabetes.blogspot.com/2016/05/general-update-on-il-2-research.html
(and the IL-2 targeted by NKTR-358 is different than the IL-21 targeted by NNC0114-0006 above.)

Company Information: http://www.nektar.com/pipeline/rd-pipeline/nktr-358
Some animal data: http://www.nektar.com/application/files/6514/9970/7031/Langowski_NKTR-358_WCI2017.pdf

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.

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

Trial of Intranasal Insulin To Prevent Type 1 Diabetes (INITII) Is Fully Enrolled

The official title is "Trial of Intranasal Insulin in Children and Young Adults at Risk of Type 1 Diabetes (INITII)" and it is now fully enrolled.  Since people will be followed for a total of 10 years, results will be ready in 2026.  However, the primary end point is after 5 years, so it's possible that those results would be published sometime after 2021.

Previous blogging is here: http://cureresearch4type1diabetes.blogspot.com/2012/09/possible-cures-for-type-1-in-news-early.html (but it's not much).  The important information is this:

Several different groups are experimenting with using insulin to prevent or cure type-1 diabetes.  This is similar to giving people with food allergies the food they are allergic to in tiny doses, gradually building up the dose over years until they are no longer allergic.  (Although the truth is a little more complex than that: type-1 diabetes is not a simple allergy to insulin.)  Because insulin is basically a protein, it gets digested, so you can't take pills of insulin.  These researchers are experimenting with inhaled insulin, given to people who are at risk of developing type-1, but have not yet developed the disease.

Clinical Trial Record: https://clinicaltrials.gov/ct2/show/NCT00336674

Results from IL-2 (the DLIT1D study)
Several groups of researchers are trying to cure type-1 diabetes by using IL-2 (Aldesleukin).  I've blogged on this before:
http://cureresearch4type1diabetes.blogspot.com/2016/05/general-update-on-il-2-research.html
The basic idea is that giving Aldesleukin raises the level of T-reg cells, and those cells kill off the bad T-killer cells, and that's good for people with type-1 diabetes.

This particular trial was aimed at finding the dose of Aldesleukin which would cause a 10%-20% increase in T-reg cells.  The technique was to give a dose of Aldesleukin to a small number of people, monitor them closely, and then based on those results, give a different dose to another small group, and so on.  After a couple of repetitions, they narrow in on the perfect dose.  This is not as easy as it sounds because Aldesleukin causes T-reg numbers to drop in the short term (which is bad), but go up in the longer term (which is good), so you need to evaluate these two effects by dose and frequency.

The researchers are happy with their results: they now know what Aldesleukin dose to use in future research, and they understand why some previous IL-2 research was unsuccessful.  Unfortunately, from my point of view, there was no improvement in C-peptide numbers or A1c numbers.  As an optimist, I'm hopeful that was because they were only testing a single dose in this trial, and improved numbers will be seen in studies with more doses over a longer period of time.

This research should lay the foundation for future clinical trials of Aldesleukin.

Abstract and Paper: http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1002139
European Trial Registry: http://www.isrctn.com/ISRCTN27852285
American Trial Registry: https://clinicaltrials.gov/ct2/show/NCT01827735

Combining Diamyd Data
(My summary: "if you combine several smaller failures, you end up with one larger failure".)

This study is a testament to the optimism of researchers.  Diamyd ("GAD Vaccine") has been tested for over 10 years.  None of these trials has been particularly successful.  They culminated in an unsuccessful Phase-III trial years ago.  You can read my previous blogging on Diamyd here:
http://cureresearch4type1diabetes.blogspot.com/search/label/Diamyd

However, researchers are natural optimists.  And it is important that they are.  Society needs optimistic researchers so that they will repeatedly attack problems, and not give up, even in the face of adversity.  In October, researchers published this paper, which basically pooled all the Diamyd data from several previous studies, and reported that it had a very small effect.  The researchers present this as a success, but the effect is so small that I consider it confirmation of failure.

People with type-1 diabetes are expected to lose insulin production during their honeymoon phase. This summary found that those given Diamyd lost 80% as much as those who were not treated.  In the last few years, several treatments have shown better results in clinical trials, and none of those have progressed to a cure, or even a treatment, so I'm not expecting this news to push Diamyd forward.  (By "better results" I mean that, when given during the honeymoon, they end up slowing beta cell destruction more than Diamyd slowed this destruction.)

Abstract: https://www.ncbi.nlm.nih.gov/pubmed/27704166


Polio Virus Trial Finished
The researchers finished gathering data in Nov-2016 so they should publish results in the next year (if successful) or two (if not).  This is an unusual trial.

The trial started in 1999, and was run by Dr. Hanna Viskari out of the University of Tampere in Finland.  These researchers believe that infection with an enterovirus would have an impact in later development of type-1 diabetes.  (It is unclear to me if they thought it would raise or lower the chance of getting type-1.)  To study this, they are following a group of 315 children who are at heightened risk of getting type-1 diabetes, because they are genetically predisposed to it.  Some of these children were given the OPV polio vaccine, which contained weakened, but still live, polio virus, while others got the IPV polio vaccine, which contains dead polio virus.  These children will be followed for 10 years to see if one group has a lower type-1 diabetes rate than the other group.

This trial is a "natural history" type trial, not an intervention trial.  Finland changed it's method of Polio vaccination, so these researchers followed children who got the "old" vaccination (OPV) to children who got the "new" vaccination (IPV).  The researchers did not randomize children to get one or the other vaccine, they merely tracked children who were already getting one or the other vaccine.

Polio is the most famous  (infamous?) enterovirus, but the family contains about 70 viruses including the Coxsackie viruses and the virus that causes Hand, Foot, and Mouth Disease.  More modern viruses in the family get numbers, rather than names, so viruses called EV-71 and EV-D68 are recently discovered enteroviruses.

Discussion
I think this study might provide general information on the relationship between enteroviruses and type-1 diabetes, but I don't think it will change people's behavior.   If the IPV polio vaccine group has a lower type-1 rate: that is already the polio vaccine that people in the US get normally.   On the other hand, if the OPV polio vaccine group has the lower type-1 rate, that vaccine has a tiny (but non-zero) chance of causing paralysis, so I don't see people switching to it in order to prevent type-1 diabetes.

Clinical trial record: https://clinicaltrials.gov/ct2/show/NCT02961595
Discussion of OPV vs. IPV: http://www.virology.ws/2015/09/10/why-do-we-still-use-sabin-poliovirus-vaccine/


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.

Research In The News (July)

This is a combination of updates from the last month or two.

DILfrequency Completes Data Collection

In late may, the DILfrequency research team announced that they had finished collecting data, and were now starting to analyse that data.  Of course, that's great news, because it implies that results will be published in the next year or two.  (In my experience successful results are published within a year, unsuccessful results often take longer, if they are published at all.)

This study is testing Aldesleukin (also called Proleukin or IL-2) by giving it to adults within 5 years of diagnosis.  IL-2 is a component of the immune system, and they hope that more it will either improve or cure type-1 diabetes.  Are are looking for changes in the immune system which occurs quickly (ie. in a few weeks), or changes in insulin, A1c numbers, or C-peptide over a three month period.

I previously blogged on this study here:
http://cureresearch4type1diabetes.blogspot.com/2016/05/general-update-on-il-2-research.html

These researchers seem to be months ahead of schedule.  Previously, they expected to finish data collection by October 2016, but they have actually finished in May 2016, which is a testament to their ability to recruit people with type-1 diabetes.  Even better, they enrolled more people than expected: 36 expected vs. 41 actual, that's 14% bigger than planned for.  This group is very media-savvy, with lots of tweeting, facebook posting, a pinterest page, etc.  I suspect that this media focus helped them recruit, and I hope it represents the future of clinical trial recruiting techniques.

https://www.facebook.com/ClinicalTrialsType1Diabetes/?fref=nf
https://twitter.com/t1diabetestrial/status/735832240513515520/photo/1

New To Me: Cord Stem Cells In A Phase-II Clinical Trial

This trial started in 2009, but it registered with the US FDA's clinical trial registry in April 2016, and I did not know about it before then.  The basic plan is to give a total of 30 people a transplant of 3rd party umbilical cord stem cells (called allogeneic umbilical cord mesenchymal stem cells).  The people treated will be honeymooners (within 12 months of diagnosis), and must have had DKA when diagnosed.  There is no control group; everyone will get the treatment.  People will be followed for three years after transplant.  Primary outcome will be insulin usage, and secondary outcomes will be C-peptide, A1c, and autoantibody counts.  The researchers hope to finish collecting data in Dec 2019.

They are recruiting at one site:
Nanjing Drum Tower Hospital of Nanjing University Medical School. Nanjing, Jiangsu, China, 210008
Contact: Dalong Zhu, MD.PhD.    86-25-83106666 ext 61430    zhudalong@nju.edu.cn  
Contact: Jing Lu, PhD.    86-25-83106666 ext 61431    qiusnow16@hotmail.com  

Clinical Trial Registry: https://clinicaltrials.gov/ct2/show/NCT02763423

Discussion

This research is similar to Haller's work at the University of Florida, which completed a phase-I and started a phase-II clinical trial also in 2009.  I've blogged on that research here:
http://cureresearch4type1diabetes.blogspot.com/2009/05/haller-cord-blood-trial-results-from.html

Unfortunately, the phase-II study (which included a control group) completed in 2012 and was published in 2013, but was unsuccessful.  Exact quote was "Autologous UCB infusion followed by daily supplementation with vitamin D and DHA was safe but failed to preserve C-peptide.".

ATG Is Unsuccessful in a Phase-II Trial

58 people recently diagnosed with type-1 diabetes were given antithymocyte globulin (ATG) in the hopes that it would modulate the autoimmune attack on the pancreas's own beta cells.    The primary end point was C-peptide generation after 2 years (a measure of the body's ability to generate it's own insulin).  People who got the treatment did no better than people who did not.

Abstract: https://www.ncbi.nlm.nih.gov/pubmed/27053235
Trial Registration: https://clinicaltrials.gov/show/NCT00515099

Discussion

Although there was no improvement if the researchers looked at everyone in the study, if the researchers only looked at older patients (between 22 and 35 years old), then they did see a statistically significant improvement in C-peptide levels as compared to untreated patients of the same age.  The researchers were hopeful that future testing might show that ATG is helpful for older patients.

Diabetes Care Has A Section On Artificial Pancreas Papers

You can read 9 AP papers in one place:
http://care.diabetesjournals.org/content/39/7?etoc
Diabetes Care is published by the ADA.

Losing Autoantibodies: Does It Happen And What Does It Mean?

It is now well established that people test positive for autoantibodies before they are diagnosed with type-1 diabetes, and (statistically) more autoantibodies are detected over time as people move closer to diagnosis.  Also, there is a big difference between having one autoantibody and having more than one.  I'm sometimes asked: can someone lose an autoantibody that they previously had?  Put another way, are autoantibodies a one way progression to type-1 diabetes? Or can people move closer or farther away from diagnosis (at least as measured by number of autoantibodies).

The answer, according to this paper:
http://care.diabetesjournals.org/content/early/2016/06/13/dc16-0181?papetoc
is "its complicated".  Basically, some people do lose an autoantibody that they previously had and therefore, at least on paper, move away from type-1 diabetes.  However, in real life, most of the people who lose an autoantibody only had one to start with, and therefore were unlikely to ever be diagnosed with type-1 diabetes.  The people with more than one autoantibody (and who are likely to be diagnosed) rarely lose an autoantibody.

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.

General Update on IL-2 Research

This is a long blog posting, because I'm attempting to summarize all the current research which attempts to cure type-1 diabetes using Interleukin-2 (IL-2).

IL-2 is a protein that the body's immune system uses for communications.  It is part of the system that helps the immune system identify the body's own cells from foreign cells.  Since the root cause of type-1 diabetes is a failure in this process, IL-2 is a possible cure.  Several different groups are testing it (or have tested it).  More information is on Wikipedia:
http://en.wikipedia.org/wiki/Interleukin_2

Of course, IL-2 cures type-1 diabetes in NOD mice:
http://jem.rupress.org/content/207/9/1871.short

Overview Of IL-2 Research

Many of these clinical trials have similar names and some of them are being run by the same researchers in the same organization.  So in the list below, I've included their FDA registration number (starting with NCT), to help me keep track of which trial is which.

Three studies have been completed:

• DF-IL2 (NCT01353833)
• DILT1D (NCT01827735)
• Combo (NCT00525889)

And three more are recruiting now:

• DFIL2-Child (NCT01862120)
• DILfrequency (NCT02265809)
• DIABIL-2 (NCT02411253)

Completed Clinical Trials

DF-IL2 (NCT01353833)

This was a "mechanistic" trial, meaning that it's goal was to show that IL-2 would increase the number and activity of good immune cells (T-reg cells).  T-reg cells regulate the immune system so that it does not self attack, and many researchers believe that getting the body to generate more T-reg cells, and making them more active, is a key to stopping the autoimmune attack.  This trial involved 25 people within two years of diagnosis.  They were divided into four groups: three getting different IL-2 doses, and a placebo group.

This first trial was successful because the researchers saw changes in the T-reg cells.  However, they did not measure C-peptide, A1c, insulin usage or any other "patient impacting" parameters, so we don't know if the T-reg changes that they saw actually resulted more natural insulin, better A1c number, etc.

This same group of researchers has started a follow on trial, called DFIL2-Child (NCT01862120) and described later.

Abstract: http://www.sciencedirect.com/science/article/pii/S0896841115000025
Abstract: http://www.sciencedirect.com/science/article/pii/S221385871370113X

DILT1D (NCT01827735)

This trial completed in May 2014, but results have not been published.  However, the researchers involved have started a follow on trial, called DILfrequency (NCT02265809) which is described later.  This trial included 40 people, within 2 years of diagnosis.  It was not blinded, and had no control group.

US Registration: https://clinicaltrials.gov/ct2/show/NCT01827735
European Registration: http://www.isrctn.com/ISRCTN27852285

Combo (NCT00525889)

This trial combined two treatments: Rapamycin and IL-2.  Rapamycin suppresses the immune system.  It enrolled 9 patients with no control group.  These people had been diagnosed less than 4 years ago, but more than 3 months ago.

This trial was not successful (in terms of moving us towards a cure).  Although it did result in more regulatory T cells, yet C-peptide numbers (a measure of the body's ability to create it's own insulin) dropped at the same time.  

Abstract: http://www.ncbi.nlm.nih.gov/pubmed/22721971?dopt=Abstract

Full paper: http://diabetes.diabetesjournals.org/content/61/9/2340.long

(Thanks to the ADA for making this paper freely available.)

Clinical Trials Currently Underway

DFIL2-Child (NCT01862120) 

This is a 24 person phase-II study, where different groups will get three different doses of IL-2, and a fourth group will get placebo.  The primary end point is a CD4 measurement 22 days after dosing. The secondary measures are more clinically useful: C-peptide numbers (which show insulin production) and A1c number.  They are also measuring changes in T-regs, to give insight into the mechanism of how IL-2 works.  The study will gather data for each participant for about 15 months.  This trial started in June 2013.  Since they completed enrollment in April-2016, they should finish collecting data by mid-2017

This trial in France and is open to children aged 7 to 14, who are in the honeymoon phase (treated with insulin for less than 3 months). Here is the contact information for this trial:
David Klatzmann, MD, PhD   Phone: +33(0) 1 42 17 74 61   Email: David.klatzmann@upmc.fr

This study is recruiting at many different hospitals:
Service d'Endocrinologie Pédiatrique -- Le Kremlin Bicetre, France, 94275
Service de Pédiatrie - CHU de Nîmes -- Nimes, France, 30029 cedex 9
CIC pédiatrique - CHU de Necker -- Paris, France, 75015
Service d'endocrinologie pédiatrique - CHU de Necker  -- Paris, France, 75015
CIC 9202 CHU Rober Débré -- Paris, France, 75019
Service d'endocrinologie Diabétologie pédiatrique CHU Robert Débré -- Paris, France, 75019

Clinical Trial Registry: https://clinicaltrials.gov/ct2/show/NCT01862120


The DILfrequency Trial (NCT02265809)

This study is testing Aldesleukin (also called Proleukin or IL-2), and uses "adaptive design". Basically, they give the early participants many small doses of the drug they are testing, and based on how and when they react to those doses, the later people in the trial get "better" doses.  (The engineering term for this is "fast feedback loop" and the software term is "agile development".)

This trial is for adults (18-70) who are within 5 years of diagnosis, so not just honeymooners.

If you really want to keep up with these researchers, they are all over twitter and facebook:
https://twitter.com/t1diabetestrial
https://www.facebook.com/ClinicalTrialsType1Diabetes

Update

Since January, this study is enrolling the last group of patients needed for completion.  There is no control group so everyone is getting the drug.  One patient has completed all follow up visits.  But the big news from my point of view, is that they are well past their "learning" phase, and are now testing doses based on the data from the earlier phases.

Once they have recruited all their patients, it will take them less than 4 months to collect their data. They hope to finish by October 2016.

I'm wondering if this clinical trial represents the future of clinical trials in an internet world.  Take a look at their list of URLs:

Web Page: http://www.clinical-trials-type1-diabetes.com/
Facebook: https://www.facebook.com/ClinicalTrialsType1Diabetes
Twitter: https://twitter.com/t1diabetestrial
Pinterest: https://www.pinterest.com/t1diabetestrial/
Clinical Trial Registery: https://clinicaltrials.gov/ct2/show/NCT02265809

Pretty soon, they will need a web page to keep track of their web pages.   From my point of view, all this information gives me a great view into the process of running the clinical trial.  Especially, it tells me when various internal milestones were reached.   Usually, I don't have any knowledge of those milestones, so it is great to see them.

DIABIL-2 (NCT02411253)

This trial is being run by the same researcher (Dr. David Klatzmann) who is running the DFIL2-Child study discussed above.  This trial is much larger (185 person), and is open to honeymooners (ie. within 2 months of diagnosis) between 12 and 35 years old.  It started in March 2015 and plans to finish in June 2018.

This trial is already recruiting in Germany, and many places in France.  It is planning to add Belgium, The Netherlands, Sweden, and Switzerland, too.

Service d'endocrinologie, diabétologie, maladies métaboliques, et nutrition, CHU de Bordeaux, Hôpital Haut Levêque Recruiting
Pessac, Aquitaine, France, 33604
Contact: Vincent RIGALLEAU, Pr.    06 63 24 45 51    vincent.rigalleau@chu-bordeaux.fr
Service d' Endocrinologie HOPITAL CAVALE BLANCHE Recruiting
Brest, Brittany, France, 29609
Contact: Emmanuel SONNET, Pr    02 98 34 71 19    emmanuel.sonnet@chu-brest.fr
Service de Pédiatrie, HOPITAL MORVAN Recruiting
Brest, Brittany, France, 29609
Contact: Chantal METZ, MD    00 33 2 29 02 00 04    chantal.metz@chu-brest.fr
Médecine pédiatrique, CHU Jean Minjoz Recruiting
Besançon, Franche-Compté, France, 59037
Contact: Anne-Marie Bertrand, Dr.    03 81 21 81 34    bertrand.anne-marie@wanadoo.fr
Service Diabétologie -Endocrinologie, CHU Jean Minjoz Recruiting
Besançon, Franche-Comté, France, 59037
Contact: Sophie Borot, Dr.    06 89 16 22 46    sophie.borot@gmail.com
Endocrinologie gynécologie diabétologie pédiatriques, Hôpital Universitaire Necker Enfants Malades. Recruiting
Paris, Ile De France, France, 75015
Contact: Michel Polak, Pr    +33 (0)1 44 49 48 02    michel.polak@nck.aphp.fr
Institut E3M, Hôpital Pitié-Salpêtrière Recruiting
Paris, Ile-de France, France, 75013
Contact: Agnés Hartemann, Pr.    01 42 17 81 18 ext 80 70    agnes.hartemann@psl.aphp.fr
Service d'Endocrinologie Pédiatrique, Hôpital d'enfants Robert Debré Recruiting
Paris, Ile-de France, France, 75019
Contact: Jean-Claude CAREL, Pr    01 40 03 53 03    jean-claude.carel@inserm.fr
Service Pédiatrie - Pôle femmes enfants, CHU de Nîmes, Hôpital Universitaire Carémeau Recruiting
Nïmes, Languedoc-Roussillon, France, 30029 Cédex 9
Contact: Tu Anh TRAN, Pr.    04 66 68 32 84 ext 32 85    tu.anh.tran@chu-nimes.fr
CHRU de Lille, Hôpital Claude Huriez Service d'endocrinologie Recruiting
Lille, Nord-Pas-de-Calais, France, 59037
Contact: Pierre FONTAINE    03 20 44 45 13    pierre.fontaine@chru-lille.fr
Service d'endocrinologie-diabétologie gynécologie pédiatriques, CHRU de Lille, Hôpital Jeanne de Flandre, Recruiting
Lille, Nord-Pas-de-Calais, France, 59037
Contact: Jacques WEILL, Pr.    03 20 44 46 95    Jacques.WEILL@CHRU-LILLE.FR
Institute of Diabetes Research, Helmholtz Zentrum München Recruiting
München, Bayern, Germany, D 80804
Contact: Annette G ZIEGLER, Pr    00 49 089 3187 2896    anette-g.ziegler@helmholtz-muenchen.de

General Discussion of IL-2 As A Cure For Type-1 Diabetes

Unfortunately, IL-2 does not have a strong history of success in previous trials aimed at type-1 diabetes.  If you look at the three completed trials: two saw some changes to T-regs, but not to "patient visible" results like C-peptides, A1C numbers, or insulin use; the other has not been published.

Of the trials currently underway, two are aimed at honeymooners, and one at long term type-1 diabetics, and all will have results in the next two years.  The trials currently underway are all gathering C-peptide data, which I consider the most important measure of progress in curing type-1 diabetes.  And they are also gathering information on A1c and insulin usage, plus various data which should show what is happening "inside" the immune system.  So I'm optimistic that with that data, it will be clear if IL-2 is worth further research or not.  Of course, when the results are reported, I'll be focusing on the results which directly impact people with type-1 diabetes: C-peptide, A1c, and insulin usage.

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 Tidepool 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.

Possible Cures for Type-1 in the News (early Sept-2012)

Phase-II Trial to Test Intranasal Insulin for Type-1 Prevention

Several different groups are experimenting with using insulin to prevent or cure type-1 diabetes.  This is similar to giving people with food allergies the food they are allergic to in tiny doses, gradually building up the dose over years until they are no longer allergic.  Because insulin is basically a protein, it gets digested, so you can't take pills of insulin.  Different groups are experimenting with different methods of getting insulin into a person, in the hopes that it will result in a cure.

This particular group is using a nasal spray.  They want to enroll 120 people, and started back in 2006, but I've not previously blogged on it.  They are now hoping to finish in late 2016.  Obviously, it's been going on for a long time.  Because it is being done in Australia (with it's lower population), I'm sure it is taking them longer than they would like to fully enroll it.

News: http://au.news.yahoo.com/today-tonight/health/article/-/14475192/diabetes-vaccine-trial
Web site: http://www.stopdiabetes.com.au/
Clinical Trial Record: http://www.clinicaltrials.gov/ct2/show/NCT00336674


IL-2 and Sirolimus Fail in Phase-I

This clinical trial failed in phase-I, in a pretty obvious way.  Here's the quote from the researchers:

Rapamycin/IL-2 therapy, as given in this phase 1 study, resulted in transient β-cell dysfunction despite an increase in Tregs.

So it hurt the patients (although only temporarily) and did not help them.   Plus they threw in this (which should really go in my "Cured in Mice" blog:

Such results highlight the difficulties in translating therapies to the clinic and emphasize the importance of broadly interrogating the immune system to evaluate the effects of therapy.

They sure do!

News: http://medicalxpress.com/news/2012-08-experimental-combo-treatment-worsens-diabetes.html
Abstract: http://diabetes.diabetesjournals.org/content/early/2012/06/15/db12-0049.abstract?sid=2b59c310-a735-4fc8-a3e1-f14f9678c935
Clinical Trial Record: http://www.clinicaltrials.gov/ct2/show/NCT00525889


Phase-I Clinical Trial of IL-2 is Complete

This is the other IL-2 clinical trial.  It involves 25 people who have had type-1 for less than 2 years.  It is complete, meaning they have gathered all the data needed, but have not yet published the results.  Since they were complete in April, if they have a positive result, I would expect publication by April 2013, and if they have a neutral, negative, or hard to interpret result, publication after that.

Clinical Trial Record: http://www.clinicaltrials.gov/ct2/show/NCT01353833

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: http://cureresearch4type1diabetes.blogspot.com
Cured in Mice Blog: http://t1dcuredinmice.blogspot.com/

New Phase-I Clinical Trial: IL-2 and sirolimus

This trial is open to people diagnosed between 3 months and 4 years ago, so it's not a classic "honeymoon only" study, but it is limited. Patients will be given two drugs over a three month period. The hope is to preserve some beta cells. This is a classic phase-I trial, looking only at safety in a small number of patients.

US Government Clinical Trials Record: http://clinicaltrials.gov/ct2/show/NCT00525889 (NCT00525889)
Immune Tolerance Network Trial Record: http://www.immunetolerance.org/studies/a-phase-i-trial-il-2-and-sirolimus-recent-onset-type-1-diabetes-mellitus (ITN018AI)
Info for patients: http://www.benaroyaresearch.org/files/webfm/diabetes/web_il2_rapa_intervention.doc
General info on Sirolimus: http://en.wikipedia.org/wiki/Rapamycin
General info on IL-2: http://en.wikipedia.org/wiki/Interleukin_2

Estimated Enrollment:	10
Study Start Date:	August 2007
Estimated Study Completion Date:	January 2012
Estimated Primary Completion Date:	January 2010 (Final data collection date for primary outcome measure)

This study is being done in Seattle Washington, and is sponsored by NIAID.

Joshua