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.

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.

Three Months Of New Clinical Trials (end of 2012)

This is a quick summary of all of the new clinical trials into type-1 that started between October 1st, 2012 and January 1st, 2013. These are trials which were entered into the FDA's clinical trial database for the first time during these three months. You can see the database here: www.clinicaltrials.com

Summary table for the last three months in 2012:

48 Total Clinical Trials
-- ----- -------- ------
 9 Artificial Pancreas  Research into systems that automatically dose based on CGM data. 
 5 CGM                  Research into Continuous (ie. Real Time) Glucose Monitoring.
 2 Transplantation      Research in "classic" transplantation (with immune suppression).
 1 Infrastructure       Research that helps or speeds up future research.  
 1 Prevention           Research aimed at lowering the number of type-1 diagnosis.
 2 Complications        Research aimed at preventing or curing type-1 complications.
10 Treatment            Research into improved BG control technology.
    3 New Test Kits
    2 Delivery
    5 New Insulin
16 Improved Control     Research that lessens the need for BG control technology.
    8 drug
    4 behavioral
    2 nutrient
    1 diet
 2 Cure                 Research aimed at curing type-1 diabetes.

So that means that 4% of new clinical trials were targeted at curing type-1 diabetes.
Both clinical trials aimed at curing type-1 were started by LCT, which I've blogged on before:
http://cureresearch4type1diabetes.blogspot.com/search/label/LCT

Below are some of my comments on some of these clinical trials:

Liraglutide (Victoza) is the Biggest Hot Spot
(but as a treatment, not a cure)

Liraglutide is a drug already approved for type-2 diabetes, however recently there has been a lot of interest in it's ability to help type-1 diabetics control their blood glucose levels.  Five of the clinical trials started in the last quarter of 2012 were testing Liraglutide on type-1 diabetics, and this is in addition to at least four trials which had previously started.

You can read more about the drug here:
http://en.wikipedia.org/wiki/Liraglutide

And my previous blogging on it here:
http://cureresearch4type1diabetes.blogspot.com/search/label/Liraglutide

Effects of Chromium Supplementation on Type-1 Diabetes

This study apparently started in 2007, but was first registered in late 2012, and they expect to finish in 2013. It will enroll 150 people. They are recruiting patients in the Shreveport, Louisiana, USA area, and it is open to people aged 8-21.

Clinical Trial Record: http://www.clinicaltrials.gov/ct2/show/NCT01709123

Exsulin (INGAP) Trial is Officially Suspended

Exsulin corporation has officially suspended their phase-II trial of INGAP (also called Exsulin).  There has not been any new news or scietific papers listed on their web site for 2 years, so I think this potential cure is pretty near to death.

My Previous Blogging: http://cureresearch4type1diabetes.blogspot.com/search/label/INGAP
Clinical Trial Record: http://www.clinicaltrials.gov/ct2/show/NCT00995540

Pet Fish for Better BG Control

One clinical trial is studying the effects of having a pet fish on blood glucose levels in teenagers. (I'm not making this up, and it's not April 1st!) Half the kids enrolled will get a picture of a fish, the other half will get an actual fish, which they are expected to take care of. A1c levels will be compared.  Here is a quote from the researchers:

There is a lack of studies assessing the impact of pet ownership on the health and well-being of adolescents. The process of caring for, loving and being loved by a companion animal could offer direct and/or indirect benefits to the HRQoL [health related quality of life] in children with T1DM. To the investigators' knowledge, there are no studies examining the impact of pet ownership on glycemic control and HRQoL in youth with T1DM.

They are recruiting in Dallas, Texas, USA.

Clinical Trial Record: http://www.clinicaltrials.gov/ct2/show/NCT01733524

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. Thanks to everyone who helps with the blog. 
Clinical Trials Blog: http://cureresearch4type1diabetes.blogspot.com
Cured in Mice Blog: http://t1dcuredinmice.blogspot.com/

History of Exsulin and AAT

Based on my last couple of posts, I got the two following questions:

How is the phase-II Exsulin study that is currently underway, different from the phase-II Exsulin study that was reported on in 2009?

The first trial gave one day's dose in one injection.  In the current trial, one day's dose is spread over three injections over the course of the day.  On one hand, the researchers think this will lead to better results, because they think that Exsulin does not stay in the system very long, so putting it in repeatedly over the day should lead to better results.  The drug will be more consistently in the system the whole day through.  On the other hand, they also think this will lead to fewer "injection site side effects".  In the earlier trial, some patients complained about pain, redness, itching, and other problems right around the injection site.  Since the second trial will only be injecting 1/3 of the dose at once, they are hoping there will be far fewer of these side effects.  They are also changing the exact formulation to try to minimize this discomfort.

Also, the first study lists the doses as 600 and 300, while the second lists them as 200 and 100.  I'm assuming that is per injection, and the daily dose was the same for each study.  But it is possible that is not true and the second trial is using a much lower dose.  If so, this would be another big difference.

The purpose of most phase-II studies is to find the best dose, the best format for that dose, and to test the treatment on a larger population than in phase-I.  So this study is testing improvements to the dosing and formulation; just what you would expect in phase-II studies.

What is AAT used for today?  Is that disease like type-1 diabetes?

AAT (Alpha 1-antitrypsin) which is also sometimes called A1AT, is approved for treating Alpha 1-antitrypsin deficiency.  Makes sense: your body doesn't produce enough AAT, so AAT is approved as a treatment.  This disease is not an autoimmune disease, and is nothing like type-1 diabetes.  It is genetic, and comes in different severities depending on if you have one or two of the bad genes .  It is estimated to affects 1 out every 2,500 people in the US, although only about 10% of the people affected are actually diagnosed.  Here is a note on the most common symptoms from the Alpha-1 Association:

The most common indicators of Alpha-1 include shortness of breath, a chronic cough, and abnormal liver test results. If you have any of these symptoms there is a simple blood test that can detect alpha-1 antitrypsin levels. This test is also recommended if you have relatives, especially siblings, who have been diagnosed with alpha-1, or if there is a family history of early emphysema, with or without smoking.

You can read about it here:
http://en.wikipedia.org/wiki/Alpha_1-antitrypsin_deficiency

And here are some support groups:
http://www.alpha1.org
http://www.alpha-1foundation.org


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.
Blog: http://cureresearch4type1diabetes.blogspot.com
To Get as Email Join here: http://groups.google.com/group/type-1-diabetes-clinical-trials-news

Possible Cures for Type-1 in the News (mid April)

Exsulin's Phase-II Trial is Data Complete 

The exact update I got on the Exsulin phase-II trial is this: "We have finished recruitment for this trial. We are still in the process of finalizing the results".  I interpret this to mean, not only have the finished recruting all their patients, but they have all their data, and are now working on the data analysis / paper writing part of the research.  This is great news, because I'm hopeful that we will hear the results in a few months.

Rituximab Starts another Phase-II Trial

Rituximab targets the CD20 part of the immune system's B cells (different from the pancreas's beta cells) to try to prevent the autoimmune attack. B cells are part of the body's immune system and communicate with the T cells, which actually attack the body's beta cells in the pancreas. By targeting the B cells, it is hoped this treatment will stop or lower the attack of the T cells.

Comment: Most treatments aimed at stopping the autoimmune attack are very focused on stopping the "bad" T cells which directly attack the beta cells in the pancreas. This treatment (if successful) opens up a whole 'nother way to stop the attack: by targeting the immune systems communication and support system, the B cells.

The current research (which I consider phase-II, although the researchers list it as phase-IV) is very similar to the a previous trial which I blogged on before (link below).  The current trial has already started enrolling 50 people at First Affiliated Hospital, Nanjing Medical University (Nanjing, Jiangsu, China). If you are interested in enrolling, contact Tao Yang, PhD at phone 86-25-83718836 ext 6466 or email yangt@njmu.edu.cn.  There is no placebo group in this trial: everyone is treated.  They started in July 2010, and hope to complete it by December 2013.  This is for people with type-1 diabetes for less than one year.

clinical trial record: http://www.clinicaltrials.gov/ct2/show/NCT01280682

A Sad Note to the Previous CD20 Research
The previous Rituximab research was led by Dr. Mark Pescovitz who died in a car crash at the end of last year.  That work was published by the prestigious New England Journal of Medicine, and was just one part of a distinguished research career.
http://www.boingboing.net/2010/12/13/mark-pescovitz-1955-.html
http://www.jdrf.org/index.cfm?page_id=114825

My previous blogging on Rituximab is here: http://cureresearch4type1diabetes.blogspot.com/search/label/Rituximab

Sitagliptin Completes Enrollment on a Phase-II Trail (as a Treatment)

This is a large (140 person) trial which started in late 2010 and is the follow on to a trial which I've blogged about before.  The goal of this is to lower A1Cs for type-1 diabetics by about 0.3, by lowering BG levels more quickly after a mean than is done now.  The 0.3 number is pretty close to what they did in an earlier, smaller trial. Sitagliptin is already approved for type-2 diabetes.  It's trade name is Januvia.

They completed enrollment in February 2011, I think.  The record is not 100% clear, and it might have been earlier.  If they did complete enrollment in February, then they will finish collecting data about June.  The clinical record says the trial will complete in July 2011, so I think it is reasonable to see results by the end of this year for this research.  This same group published their previous results very quickly after the study was done.

Clinical trial: http://www.clinicaltrials.gov/ct2/show/NCT01227460
Previous trial: http://www.clinicaltrials.gov/ct2/show/NCT00978796
Results from related trial: http://cureresearch4type1diabetes.blogspot.com/2011/02/possible-cures-for-type-1-in-news-late.html (but this was combining this drug with another)

Extra Reading

Dr. Skyler has written a wonderful summary of some of the more interesting clinical trials in type-1 diabetes done between June 2009 and July 2010:
http://onlinelibrary.wiley.com/doi/10.1111/j.1742-1241.2010.02580.x/full
One of the things I particularly liked about this paper, is that for each clinical trial, there is a summary of the abstract and then Dr. Skyler's comments.  These comments often put the research into context, discuss next steps, or give his opinions on it.  That perspective is missing from the raw scientific papers.  (Although he wrote this before the two anti-CD3 treatments had failed in phase-III trials, so those are discussed here, although they are already dead as cures.)

Here is part of his summary of the whole year:

That negative studies continue to dominate the field, and that the positive ones still show decline in β-cell function over time, has led to more calls for combination approaches. When I [Dr. Skyler] have advanced such prospects at meetings of paediatric diabetologists, I hear groans. Yet when I have advanced these prospects at meetings of immunologists and transplant surgeons, I hear cheers.

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.
Blog: http://cureresearch4type1diabetes.blogspot.com
To Get as Email Join here: http://groups.google.com/group/type-1-diabetes-clinical-trials-news

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

Diamyd Finishes Enrollment of their European Phase-III Trial

Diamyd has finished enrolling patients in their 300 person, phase-III European trial. Diamyd is a vaccine like treatment designed to train the body's immune system not to attack itself and is focused on GAD65, which is the most common antibody marker carried by people with type-1 diabetes. Several human trials have already completed, and several more are in process. This trial is newly diagnosed type-1 diabetics, only.

Why is finishing enrollment important? For a couple of reasons:

1. Once a trial is fully enrolled, everyone knows when it will end, or at least when they will finish gathering the required data. So in a very real sense, we can see the end of the tunnel now. This trial lasts 15 months, so the last person who enrolls in Nov-2009 will finish with the protocol in Feb-2011.
   
2. Phase-III is the last phase before marketing approval of a new drug, so these guys are now the treatment second closest to general availability. (DiaPep227 Phase-III fully enrolled a few months ago.)

These guys also have a similar, large phase-III trial going on in the US, and they are still recruiting for that one. Plus, there are other clinical trials by different people using the same drug.

More info:
http://www.pipelinereview.com/index.php/2009111230708/Vaccines/Diamyds-European-Phase-III-Study-Fully-Recruited.html

Exsulin Update: Vague Results and Another Phase-II Trial Starting

This news is actually from the Summer, but I haven't blogged about it before, so here it is:
Here is the highlight of the results from their last batch of clinical trials:

In the T1DM study (SPIRIT 1), Arginine-stimulated C-peptide (AUC0-30) significantly increased from baseline in the 600 mg group (p = 0.0058 versus placebo)

My translation: the treatment caused people to generate more of their own insulin in response to a meal, when given 600mg. There was a second group that got 300mg, but they did not see any benefit. The full paper includes more detail one what was seen, but it looked pretty small to me.

Of course, the good news, is that this clinical trial only took them a few months to run, so they could easily make improvements to their process, and try it again. And that is what they are going to do:

The new phase-II trial is already recruiting it's 30 participants and they are hoping to have results by Q2 2010. Because INGAP does not stay in a person's system for very long, in this trial they will give smaller doses three times a day (rather than larger doses once a day), and therefore hope to have better effects and fewer side effects. They have also changed the formulation to have less irritation at the injection site. In their previous study, 25% of the people who got the higher dose, dropped out of the trial because of "adverse effects" (often this irritation), so that is a problem they want to address.

Abstract of research of completed phase-II trail:
http://www3.interscience.wiley.com/journal/122518238/abstract

Press release:
http://www.medicalnewstoday.com/articles/161069.php

Clinical Trial record for new phase-II trial:
http://www.clinicaltrials.gov/ct2/show/NCT00995540

I want to particularly thank fellow BraveBuddy Ricardo Dolmetsch for providing a lot of of the information that I used to report results from the previous trial and for providing some useful insight. Also thanks to ChildrenWithDiabetes member Ellen for pointing out the second phase-II study.

Phase-II Results from DiaPep227

DiaPep227 entered phase-III trials before I started to track clinical trials, so I've never blogged about their Phase-II results. However, since they're phase-III was the first to be fully enrolled, I thought it might be interesting to look at their previous results. Here is the quote from their abstract:

At 18 months, stimulated C-peptide concentrations had fallen in the placebo group (p = 0.0005) but were maintained in the DiaPep277 group. The need for exogenous insulin was higher in the placebo group than in the DiaPep277 group. Mean HbA_1c concentrations were similar in both groups. After extension of the study, patients continuing treatment with DiaPep277 and those switched from placebo to DiaPep277 manifested a trend towards a greater preservation of beta-cell function compared to patients maintained on or switched to placebo. The safety profile of DiaPep277 was similar between the treatment and placebo groups, and no drug-related adverse events occurred.

When I look at that summary, the first thing that I notice is that there are no numbers in the results (except a p value, which isn't a result, its a measurement of a result). It talks about C-peptide and A1C numbers, but does not give them. For me that is a big red flag. Vague qualitative statements ("need for exogenous insulin was higher") don't give me confidence. I want to know how much more insulin? And I don't see that data here. Exsulin's abstract in the news item above had the same problem, and reading the whole paper just reinforced by belief that no numbers in the abstract does not bode well for the strength of the results.

The complete paper is pay-per-view, so I'm just working off the abstract.

Abstract of research:
http://www3.interscience.wiley.com/journal/113488533/abstract

All the views expressed here are those of Joshua Levy, and nothing here is official JDRF news, views, policies or opinions.

Exsulin: New Phase-I Research Almost Ready to Start (for Non-Honeymoon Type-1 Diabetes)

The Exsulin company is hoping to start Phase-I human trials in June 2009 (so right soon now). They are testing a new formulation of INGAP called Exsulin, a drug designed to regrow beta cells in the pancreas.

Their Phase-I clinical trial is small, short, and open to people who have had type-1 diabetes for more than 2 years, so we should have some results soon. It is a three group design. One group gets nothing, one gets a full dose, the other gets a half dose. They are checking for all the right stuff: C-peptide, fasting glucagon, fasting glucose, total daily insulin dose, and HbA1c. They are using two sites Montreal and Rochester.

This is described on their web site:
http://www.exsulin.com/underway.html

INGAP (now renamed Exsulin) has a 12 year history of research. NOD mice trials worked well, but human trials didn't show much success (sound familiar?) The phase-I study is described here: http://www.clinicaltrials.gov/ct2/show/NCT00034255. The phase-II study is described here: http://www.clinicaltrials.gov/ct2/show/NCT00071409. It was funded by Proctor and Gamble but the results were not good enough to move forward.

The original developers of INGAP got back rights to it after P&G didn't like the phase-II results. Their analysis of the results convinced them that INGAP was helping grow new beta cells, but that those new cells were being killed off too quickly to help the patient. (Maybe because of the body's immune system, or maybe because of inflammation, or maybe for some other reason.) So it is natural for them to pair Exsulin with another drug to treat the other problem, and see if both together can cure type-1 diabetes. But the research they are starting now is just Exsulin, not paired with anything.

Joshua Levy

DiaKine starts Phase-I clinical trials on Lisofylline (LSF)

DiaKine is about to start it's first clinical trial in a research program aimed at curing type-1 diabetes. Their treatment is Lisofylline (LSF), an anti-inflammatory drug that (in NOD mice) has prevented type-1 diabetes and (when given with exendin-4) cured existing type-1 diabetes.

Previously (in May 2008) DiaKine has formed a joint project with Kinexum Metabolics, to run a human trial (phase-II) using both of their drugs together (LSF and INGAP). The combination had already given good results in NOD mice. That trial was supposed to start in "late 2008". Kinexum Metabolics has since changed it's name to Exsulin (not INsulin, but EXsulin. Get it?) I can't find any record of the LSF+INGAP trial starting, but each company is testing it's own stuff seperately, so maybe after that, they'll test them together. I know a lot of people are interested in an anti-inflammatory and a beta-cell growing combination therapy, and obviously these two companies are interested in that, also. In any case, this trial is LSF only, not the combo they talked about earlier.

The current trial involves 8 people, and is supposed to start in May 2009 and be done by December 2009.

This research is being done in New Jersey.

You can read a news article here:
http://www.earthtimes.org/articles/show/diakine-therapeutics-diabetes-immune-modulator-drug-set-for-human-clinical-trial,821004.shtml

The US FDA's clinical trial record is here:
http://clinicaltrials.gov/ct2/show/NCT00896077

And the official press release is here (and is better than most):
http://www.diakine.com/assets/news20090512.pdf

The press release talking about LSF+INGAP together is here:
http://www.diakine.com/assets/news20080506.pdf

I want to thank the Wainscoat family for bringing this to my attention.

Joshua Levy