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

Beta Cells Which Hide From The Immune System

This has not progressed to clinical trials, but it is a new approach.  There is a lot of ongoing research into creating beta cells which will generate insulin in response to blood glucose, and many people talk about these as though they were a cure.  But they aren't, at least not by themselves, and for two reasons.  First, as a foreign cell they are properly attacked by the immune system.  Second, type-1 diabetes is caused by the immune system improperly attacking beta cells.  So there are two reasons why the T1D immune system is going to attack and destroy these cells.

However, the Salk Institute has found a recipe which takes stem cells and creates functional beta cells which are invisible to the immune system.  They call them "Immune-evasive".  In theory, this could protect the cells from both kinds of immune system attack, and these cells could, by themselves, cure type-1 diabetes.

Obviously, I'm going to be very interested in the research when/if it moves to human trials.  The press release from Salk makes it clear that these cells are not even ready for human trials, yet.  They need to undergo another round of animal testing, and then they can start the 10-15 years of human trials required for approval.

 

This is exactly the kind of research where human trials are important.  They are trying to create human cells which are hidden from the human immune system, but they must work in mice to start with.  So they are working with a specific kind of mouse called a NOD/SCID mouse.  The NOD refers to mice which have autoimmune diabetes.  NOD mice are the standard mice used to research cures to T1D.  The additional "SCID" refers to mice in which it is possible to experiment with human cells, because their immune systems have been modified to allow it.  So NOD/SCID mice are quite different than NOD mice.  That is a two edged sword.  The researchers must do it, because they can't start out experimenting on people, and yet they need to create human cells.  But SCID is a big change to the mouse immune system, changing three basic types of immune cells.  So this research is not going from mice to humans, it is going from highly modified mice to humans.  For me, this is an even larger jump, so the first human results are even more important. 

News Articles: https://www.sciencedaily.com/releases/2020/08/200819110923.htm

Press Release: https://www.salk.edu/news-release/first-immune-evading-cells-created-to-treat-type-1-diabetes/

Scientific Article:  https://www.nature.com/articles/s41586-020-2631-z

 

No Results from A Phase-I Trial of Ustekinumab

In 2014 a Phase-I clinical trial started to test Ustekinumab on people with honeymoon type-1 diabetes.  They completed enrollment  on May 24, 2016, which means they should have finished gathering data by May 24, 2017 and published results by May 2018.  Successful results are usually published in less than a year after completion.  But now it is well past May 2020, and I can not find any results from the study.

  

From my point of view, this means the study was unsuccessful.

You can read my previous blogging on this treatment here:

https://cureresearch4type1diabetes.blogspot.com/search/label/Ustekinumab

I think there have been a total of  three studies done on Ustekinumab, but only one is still active.  That one is in the UK and expected to finish in Oct-2022.  You can read more about it here:

https://www.type1diabetesresearch.org.uk/current-trials/ustekid/

Clinical Trial Registry: https://clinicaltrials.gov/ct2/show/NCT02117765

 

Reminder: Once Weekly Basal Insulin Under Development

This is not a cure, but I'm sure some people will find it interesting.  Novo Nordisk has finished phase-II trials on an insulin that you use once a week to cover your basal needs.  You still need to take insulin for meals, but it replaces daily (or twice a day) basal insulin injections with just one injection a week.  It is called Insulin Icodec, and still needs to go through phase-III clinical trials before it is approved for use.

Fun Web Article on the History of Clinical Trials

https://getpocket.com/explore/item/the-fascinating-history-of-clinical-trials?utm_source=pocket-newtab

 

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 (June)

This blog posting is a summary of four small updates.  Unfortunately, they include research delay, two unsuccessful trials, and one trial unreported for so long that I'm now assuming that it failed.

Tianhe Delays Phase-II Trial of Stem Cell Educator

You can read my previous blogs on Tianhe's Stem Cell Educator here:

https://cureresearch4type1diabetes.blogspot.com/search/label/Stem%20Cell%20Educator

The quick summary is that the stem cell educator is a machine which takes the immune cells from a person's blood, exposes them to various organic molecules which change their behavior so they learn not to attack beta cells. The cells are then returned to the body.

Unfortunately, the new news is that clinical trials for the Stem Cell Educator have been delayed by three months because of the COVID-19 pandemic.  You can read the announcement here: https://www.facebook.com/tianhecell/posts/1149765802041857

I suspect that some other clinical trials are getting delayed as well, but since there is no central clearing house for these kinds of announcements, it is hard to know for sure.

Also new (to me) is that Dr. Zhao has a fund raising page through the hospital where he does his research.  So if you want to fund his research directly, you can do it here:

https://secure2.convio.net/humc/site/Donation2;jsessionid=00000000.app20058a?4622.donation=form1&DONATION_LEVEL_ID_SELECTED=1&NONCE_TOKEN=F031AB361B3FAE40A58FDBF166E9EE74&df_id=4622&idb=0&mfc_pref=T&fbclid=IwAR0fYn6E7Y--EzfHeoR5rcNLKdQK-3WWUrgywEZH6zPZEVx2EI8N87tg6Xo

Unsuccessful Phase-II? Study of Albiglutide

Albiglutide (tradenames Eperzan and Tanzeum) is a GLP-1 inhibitor, similar to Byetta, Victoza and other drugs commonly used by people with type-2 diabetes.  GlaxoSmithKline tested it in people with type-1 diabetes, to see if it had the potential to delay T1D or cure them.

Unfortunately, it was not successful.  Their conclusion was:

In newly diagnosed patients with type 1 diabetes, Albiglutide 30 to 50 mg weekly for 1 year had no appreciable effect on preserving residual β-cell function versus placebo.

I previously blogged about this research here:

https://cureresearch4type1diabetes.blogspot.com/2016/01/research-in-news-january.html

Clinical Trial Record: https://clinicaltrials.gov/ct2/show/NCT02284009
Wikipedia: http://en.wikipedia.org/wiki/Albiglutide

Unsuccessful Phase-II for Low-dose IL-2

Interleukin 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.

This study enrolled 24 children in their honeymoon phase into 4 different groups: one placebo group and three different treatment groups.  The primary outcome was higher levels of a specific immune cell called a Treg cell.  Higher levels of Tregs are thought to help prevent T1D.  Secondary outcomes included direct measures of T1D: how much insulin the person produced naturally (as measured by C-peptides) and A1c numbers.

The study showed that treated honeymooners did generate more Tregs. This result was statistically significant and was higher in the higher dose treatments.  However, the secondary outcomes (which measured effect on T1D symptoms) were not statistically significant.

In 2016, I published a blog which was a summery of the 6 clinical trials using IL-2 at that time:

https://cureresearch4type1diabetes.blogspot.com/2016/05/general-update-on-il-2-research.html

You can read all my blogging on IL-2 here:

https://cureresearch4type1diabetes.blogspot.com/search/label/IL-2

My informal summary of all this research is that IL-2 causes more Tregs to be generated, but does not cause more insulin to be made, or impact A1c.  The key measure of progress to a cure is how much insulin a person is naturally creating and (so far) IL-2 is not increasing that.

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

Abstract: https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3384899

Whole Paper: https://poseidon01.ssrn.com/delivery.php?ID=292084092121074084075006078065124119003088025016027009096102007033048103037118051096057092059036018012018012106018002009032090052021085105123103112121126100107039085023106102024117103092096081021001102126003094018118025077005022012013064085005024&EXT=pdf

Unsuccessful Phase-I Study of Ustekinumab and INGAP: No Results After Three Years

My policy is that any study which has not published within two years of completion is unsuccessful.  My experience has always been that studies that are successful are published quickly: within one year.  So when a study goes three years, as this one has, without publishing its results, I'm very comfortable assuming that it was unsuccessful.

I have tried, more than once, to contact the researchers involved to get an update, but never got a reply.

Previous Blogging: https://cureresearch4type1diabetes.blogspot.com/2016/01/exsulin-ustekinumab-combo-starts-phase.html

Clinical Trial Registry: https://www.clinicaltrials.gov/ct2/show/NCT02204397

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.

Ustekinumab Starts A Phase II Clinical Trial Called USTEKID

Ustekinumab was approved in the US in 2009 for treating psoriasis, which is an autoimmune disease (where the immune system self attacks skin cells rather than pancreas cells, as with type-1).  It has also been tested on multiple sclerosis, Crohn's disease, and sarcoidosis (also all autoimmune diseases).  Ustekinumab is thought to work by blocking inflammation, and specifically blocking two immune molecules called IL-12 and IL-23.

The USTEKID Trial

This trial will enroll 72 adolescent (aged 12-18) honeymooners (within 100 days of diagnosis).  2/3s of them will get the drug (an infusion of Ustekinumab) once every two months for almost a year, and the other 1/3 will get a placebo, as a control group.  The study will use C-peptide in response to a meal as a primary end point (measured one year after start of treatment).  There are also a bunch of secondary end points.

The first patient started the trial in Dec-2018 and they hope to finish by Oct-2022.

Web site: https://www.type1diabetesresearch.org.uk/current-trials/
European Clinical Trial Registration: http://www.isrctn.com/ISRCTN14274380
EudraCT number: 2018-000015-24

Sites

Primary contact: Dr Kym Thorne
Floor 2, ILS2, Swansea University Medical School
Swansea, SA2 8PP, United Kingdom
+44 (0)1792 606372     k.thorne@swansea.ac.uk

Participating Locations:
(Note that not all sites are recruiting all ages, and not all have opened as yet.)

• Royal Aberdeen Children’s Hospital, Westburn Road, Aberdeen, AB25 2ZG
• Countess of Chester Hospital, Liverpool Road, Chester, CH2 1UL
• Tayside Children's Hospital, Ninewells Hospital, Dundee, DD1 9SY
• Royal Devon and Exeter Hospital, Barrack Road, Exeter, EX2 5DW
• Royal London Hospital (Barts), Whitechapel Road Whitechapel, London, E1 1BB
• University College Hospital London, 250 Euston Road, London, NW1 2PG
• University Hospital of Wales, Heath Park, Cardiff, CF14 4XW
• Noah’s Ark Children’s Hospital of Wales, Heath Park, Cardiff, CF14 4XW
• Evelina Children’s Hospital, St Thomas' Hospital, Westminster Bridge Road, London , SE1 7EH
• St James’ Hospital, Beckett Street, Leeds, LS9 7TF

This study is supported by National Institute for Health Research (NIHR) (UK), and is part of the ADDRESS-2 network, which is funded by JDRF.

Other Ustekinumab Studies
You can read my previous blogging on Ustekinumab here:
https://cureresearch4type1diabetes.blogspot.com/search/label/Ustekinumab

Both of these studies have the same warning signal.  Both completed over a year ago, but have not yet published their results.   My experience is that studies which are successful publish quickly, usually within a year of completion, so the fact that these researchers have not yet published is a bad sign.

Ustekinumab and INGAP
A small combination study of Ustekinumab and INGAP started in November 2015 and ended in March 2017, but the results have not yet been published.
https://clinicaltrials.gov/ct2/show/NCT02204397

Phase-I Clinical Trial For Ustekinumab
A 20 person phase-I trial for Ustekinumab started recruiting in March 2015 and finished recruiting in May 2016 and therefore should have completed after May 2017, but the results have not yet been published.
https://clinicaltrials.gov/ct2/show/NCT02117765


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.

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

Ustekinumab Is Fully Enrolled

Ustekinumab, an immune modulating drug, started a Phase-II? trial in July 2014.  I previously blogged about it here:
http://cureresearch4type1diabetes.blogspot.com/search/label/Ustekinumab

They completed enrollment on May 24, 2016, which means they should finish gathering data by May 24, 2017, because they need to gather data for a year.  Successful results are usually published in less than a year after completion.

This drug was approved in the US in 2009 for treating psoriasis, which is an autoimmune disease (where the immune system self attacks skin cells rather than pancreas cells, as with type-1).  It has also been tested on multiple sclerosis, Crohn's disease, and sarcoidosis (also all autoimmune diseases).  Ustekinumab is thought to work by blocking inflammation, and specifically blocking two immune molecules called IL-12 and IL-23.

Clinical Trial Record: https://clinicaltrials.gov/ct2/show/NCT02117765

In July, A Phase-II? Verapamil Trial Was 20% Enrolled
A research group at the University of Birmingham (Alabama) is testing Verapamil on people in the honeymoon period.  The hope is that Verapamil will cause beta cells to naturally regrow.  I've previously blogged on this research here:
https://cureresearch4type1diabetes.blogspot.com/search/label/Verapamil

They have been recruiting for over a year, but have only enrolled 12 people, out of the 52 they need. At this rate, they will not be fully enrolled within 2 years as they had hoped, and that's a problem.

The drug they are testing is already approved (and pretty widely used) for high blood pressure, so it should not be that hard to recruit for this study.  However, only adults can be recruited (per FDA rules).  Obviously, limiting recruitment to adults still in their honeymoon phase makes this process much more difficult, since most honeymooners are youth, not adults.

Terminated: Leptin by Garg at University of Texas

On June 23, 2015 a Phase-I trial of Leptin being run by Dr. Garg at the University of Texas, was cancelled.  The clinical trial record says terminated at the request of the sponsor.  Since it was being sponsored by JDRF and by Amylin (which makes Leptin), I assume that Amylin shut down the research. You can read my previous blogging here:
http://cureresearch4type1diabetes.blogspot.com/search/label/Leptin

At one time they were going to dose 15 people, but they ended up only dosing 7.   It was a Phase-I, pilot study, so there was no control group.  The researchers do hope to publish results, and I'll blog on them when they come out.

Clinical Trial Record: https://clinicaltrials.gov/ct2/show/NCT01268644


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.

Exsulin / Ustekinumab Combo Starts Phase-I Clinical Trial

Exsulin is a drug designed to trigger beta cell growth and Ustekinumab is designed to modulate the immune system.  These researchers are testing them together as a combination cure for type-1 diabetes.

My previous blogging on Exsulin (previously called INGAP) is here:
    http://cureresearch4type1diabetes.blogspot.com/search/label/INGAP
    http://cureresearch4type1diabetes.blogspot.com/search/label/Exsulin
My previous blogging on Ustekinumab is here:
    http://cureresearch4type1diabetes.blogspot.com/search/label/Ustekinumab

The Trial

The trial is on 5 people with no control group.  It started in Nov-2015 and will finish in June-2017.  It is open to adults who have had type-1 diabetes between 2 and 10 years, so this is for established type-1 diabetes, not honeymooners.  The people in the trial will get two injections of  Ustekinumab (one month apart) and twelve weeks of daily Exulin injections.

Results will be measured after six months.  The primary outcomes are "safety and tolerability" while the secondary outcomes are various C-peptide measures and one A1c measure.

This trial is recruiting at the Montreal General Hospital (Montreal, Quebec, Canada):
Contact: George M. Tsoukas, MD    514 934-8017    g.tsoukas@gmail.com
Contact: Louise Ullyatt, RN    514-934-1934 ext 42115    lullyatt@gmail.com
 

Discussion

Exsulin (INGAP) is a treatment with a history.  It's gone through two major cycles of clinical trials, and neither one panned out.  The researchers think that this was because Exsulin was stimulating beta cell growth, but these new beta cells were destroyed by the autoimmune attack, so even though the Exsulin was working, it was not benefiting the patients.  They are optimistic that by pairing it with an immune modulator (Ustekinumab), patients will see the benefit.

Obviously, five people is a very small trial.  However, since these are established, adult type-1 diabetics, they should have consistently very low C-peptide numbers.  Any increase should be noticeable and would be important.

It will be interesting  to compare these results to the Ustekinumab honeymoon results.  Honeymoon is a time when the body is still naturally producing enough insulin to make a difference, so comparing Ustekinumab+honeymoon to Ustekinumab+Exsulin will tell us something about Exsulin  (or maybe effective Ustekinumab doses).  The Ustekinumab trial is scheduled to finish in March.  However, that study is still listed as recruiting and needs 20 adult honeymooners (which is a tough recruitment goal). So it might take longer than expected.

News Article: http://medicalxpress.com/news/2015-11-clinical-trial-diabetes-jgh-muhc.html
Press Release: http://www.eurekalert.org/pub_releases/2015-11/mu-lct112515.php
Clinical Trials: https://www.clinicaltrials.gov/ct2/show/NCT02204397

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.

Secukinumab and Ustekinumab each start Phase-II Trials

Secukinumab and Ustekinumab have a lot in common, including both starting phase-II trials in the last few months, so I'm covering them together.  Both of these drugs are monoclonal antibodies, meaning they are specifically targeted at one kind of immune cell.  (Approximately 1/3 of all new drugs in the US are monoclonal antibodies, so this is not unusual.)  In both cases the drugs have already done phase-I trials for other diseases, so the phase-II trials described here are the first times these drugs have been tested on type-1 diabetes.

Soundtrack for this blog posting: http://grooveshark.com/#!/s/The+Chain/1Ty1wz

Secukinumab

This drug has been submitted to the FDA for approval for treating moderate-to-severe plaque psoriasis (an autoimmune disease), but has not yet been approved.  It has also been tested for some other autoimmune diseases.   Secukinumab is thought to work by blocking inflammation, specifically blocking IL-17, an immune molecule.  Secukinumab was known as AIN457 during development.

The trial has started recruiting, and is expected to run until April 2019, enrolling 100 people.  Half will get the drug, half will be in a placebo group (randomized, double blind).  The primary end points are safety and C-peptide generation after a meal.  Secondary end points include A1c, insulin usage, etc.  This study is funded by Novartis Pharmaceuticals.  They are recruiting people at least 15+ locations all over the US.  Unfortunately, none of them are in the San Francisco bay area.

Clinical Trial Record: http://clinicaltrials.gov/ct2/show/NCT02044848

Wikipedia: http://en.wikipedia.org/wiki/Secukinumab

Ustekinumab (Stelara)

This drug was approved in the US in 2009 for treating psoriasis, which is an autoimmune disease (where the immune system self attacks skin cells rather than pancreas cells, as with type-1).  It has also been tested on multiple sclerosis, Crohn's disease, and sarcoidosis (also all autoimmune diseases).  Ustekinumab is thought to work by blocking inflammation, and specifically blocking two immune molecules called IL-12 and IL-23.

This trial will run from July 2014 to March 2016, and will enroll 20 people, in 4 groups of 5 people. There is no control group; each group will get a different dose of the drug.  The primary end points are all safety related, the secondary endpoints are all immunology related, but there are "exploratory" endpoints which are the results a person with type-1 would care about: C-peptide measurements, insulin usage, and A1c.  The study is being done at the University of British Columbia, by a professor in their dermatology department.  I assume he has experience with the drug's use on psoriasis. It is funded by JDRF.

Clinical Trial Record: http://clinicaltrials.gov/ct2/show/NCT02117765

Wikipedia: http://en.wikipedia.org/wiki/Ustekinumab

Discussion 

These studies brought up two points for me:

First: They show the power of money and capitalism in getting research done.  The JDRF (a non profit) is funding the Ustekinumab study, and they can only afford to dose 20 people (no placebo group).  On the other hand, the Secukinumab study is funded by industry, and they are dosing 50 people and in addition have a full placebo group.  It is nice to have money.

Second; conspiracy theorists will need to ignore the Secukinumab study, because it doesn't fit with their "corporate America is making too much money to cure type-1" theory.  That study is being funded by Novartis Pharmaceuticals, which makes a huge amount of money off diabetics.  It is a classic "Big Pharma" company, yet here it is funding a drug that might be a cure for type-1.  Why?  Because they think they can make more money faster by curing type-1, than by treating it.  And they are afraid that if they don't, someone else will, and they'll be left with nothing.  The other company will get all the money from the cure, and they will be left with no one to treat.  Die hard conspiracy  theorists will say "they're funding the trial just to bury it", but if that were true, why fund it at all?  Running a human trial in the US right now, requires public disclosure.  If they really wanted to run some secret trial, they'd be doing it in Russia, China, or some country that didn't have public registry requirements.

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.