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.
Showing posts with label Aldesleukin. Show all posts
Showing posts with label Aldesleukin. Show all posts
Wednesday, January 25, 2017
Sunday, May 1, 2016
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:
Clinical Trials Currently Underway
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)
- DFIL2-Child (NCT01862120)
- DILfrequency (NCT02265809)
- DIABIL-2 (NCT02411253)
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 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
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
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.
(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.
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
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.
Wednesday, June 26, 2013
Possible Cures for Type-1 in the News (June)
Aldesleukin (Proleukin) Starts a Phase-II Clinical Trial
Called DILD1T, this is a 40 person clinical trial. It started in March 2013, and is expected to finish in January 2015. It is enrolling adults who have had type-1 diabetes for 3-24 months (so not just honeymooners) in Addenbrooke’s Hospital, Cambridge, UK. Currently, it is only 12% enrolled, so they have a ways to go. I'm treating this as a phase-II trial, because of it's size and because Proleukin has already been tested twice in type-1 diabetics (that I know of).
I think that this study involves only one subcutaneous injection (like an insulin injection).
Here is the justification for the study. The quote is from the researchers, but I've removed some of the medical language:
Here are links for this new research:
Web sites: http://www.clinical-trials-type1-diabetes.com http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=13846
News: http://www.wellcome.ac.uk/News/Media-office/Press-releases/2013/WTP052844.htm
Facebook: https://www.facebook.com/ClinicalTrialsType1Diabetes
Twitter: https://twitter.com/t1diabetestrial
WHO Registration: http://www.controlled-trials.com/ISRCTN27852285/
US Registration: http://www.clinicaltrials.gov/ct2/show/NCT01827735
Wikipedia on IL-2: http://en.wikipedia.org/wiki/Interleukin_2
I also think it is important to remember that IL-2 has been tested in humans twice before, and has failed both times. I previously blogged on those trials:
http://cureresearch4type1diabetes.blogspot.com/search/label/IL-2
Clinical Trial Records:
http://www.clinicaltrials.gov/ct2/show/NCT00336674
http://www.clinicaltrials.gov/ct2/show/NCT00525889
DiaPep 277's Results from an Extended Phase-III Trial:
No Longer a Cure?
I've been following DiaPep 277 for as long as I've been following type-1 diabetes cures. When I started, it was already in phase-II trials. Recently Andromeda Biotech Ltd, the company developing it, has published some phase-III results, and (most recently) some extended phase-III results. These extended results are from people who were in the phase-III trial for two years, and then continued with the treatment for an additional two years. The two year extension was "open label", meaning that the patients and doctors knew they were getting the treatment; it was not blinded.
Unfortunately, the results are decidedly mild. People's A1C numbers dropped by 0.6 (from an average of 7.6 to an average of 7.0. In terms of improvement of treatment, that's not bad. I think there is a market for a drug that would lower A1C numbers that amount, but it is not a cure. There is always hope that future improvements in the treatment will lead to even better A1C improvements (which I think is likely), or even improvements so great they lead to a cure (which I think is very unlikely). But currently, this is an adjunct treatment, not a cure. So I expect to stop covering DiaPep 277, unless I see results much larger than are seen here.
news: http://www.globenewswire.com/news-release/2013/06/05/552188/10035325/en/Andromeda-Announces-the-Results-of-an-Extension-to-Its-Phase-III-Study.html
The previously announced results from one of their phase-III trials, which I blogged about here:
http://cureresearch4type1diabetes.blogspot.com/2011/11/andromedas-diapep277-succeeds-in-phase.html
were similarly mild, and much more like a treatment than like a cure.
Phase-I Trial Resets the Immune System in MS Patients
This news comes from a human trial in multiple sclerosis (MS) patients. Basically, researchers were able to "reset" the body's immune system, to lower the autoimmunity reaction (the body's attacking it's own cells) by 50%.-75%. This was in a 9 person phase-I trial in Germany.
To understand why that is important, a little background is needed. Most researchers believe that MS and Type-1 are related diseases. In both cases the immune system mistakenly attacks the body's own cells. In Type-1, it attacks beta cells in the pancreas, and in MS it attacks the myelin sheaths of nerve cells, however the underlying autoimmunity reaction is similar.
Prior to testing on people, this method was tested in mice who had MS and in mice who had type-1 diabetes, and worked on both groups of mice. However, the human trials were MS only. But obviously, trials in type-1 diabetic people could be done as well. In my opinion, should be done.
The idea of resetting (or rebooting) the body's immune system has been tried on type-1 diabetics, and it was successful. Some of the treated type-1 diabetics did not have to inject insulin for years afterwards. However, the risk involved is high enough, that these treatments have never moved forward. At least three different teams (in Brazil, Poland, and China) have run similar trials and gotten similar results. I have blogged about them before:
http://cureresearch4type1diabetes.blogspot.com/search/label/Burt
Although it is hard to draw a direct comparison, it sounds like the procedure being tested here is much safer, but slightly less effective than the procedure used by Burt, Snarski, Li, etc. Of course, it might be refined over time to make it more effective or safer, or both.
news: http://scienceblog.com/63715/big-multiple-sclerosis-breakthrough/
Personal Note
In the past, I've posted on my blog what I call a "non-conflict of interest statement" which is this:
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 daughter has type-1 diabetes and participates in clinical trials. 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/
Called DILD1T, this is a 40 person clinical trial. It started in March 2013, and is expected to finish in January 2015. It is enrolling adults who have had type-1 diabetes for 3-24 months (so not just honeymooners) in Addenbrooke’s Hospital, Cambridge, UK. Currently, it is only 12% enrolled, so they have a ways to go. I'm treating this as a phase-II trial, because of it's size and because Proleukin has already been tested twice in type-1 diabetics (that I know of).
I think that this study involves only one subcutaneous injection (like an insulin injection).
Here is the justification for the study. The quote is from the researchers, but I've removed some of the medical language:
The vast majority of genes that contribute to susceptibility to type 1 diabetes [are related to] immune regulation and function. In particular, ... the interleukin 2 (IL-2) pathway that regulates T cell activation .... Aldesleukin (Proleukin) is a human recombinant IL-2 product .... There is substantial [research data in tissues/petri dishes, animals, and humans] that ultra low dose IL-2 (aldesleukin) therapy can arrest the autoimmune mediated destruction of pancreatic beta cells by [encouraging] functional T regulatory cells.The researchers view this study as looking for the optimal dose as a prelude to doing a large phase-III trial. This is a classic goal of many phase-II trials. This trial is funded by the Welcome Trust (a big UK operation), JDRF, and the NHS Foundation Trust (which I think is the UK government).
Here are links for this new research:
Web sites: http://www.clinical-trials-type1-diabetes.com http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=13846
News: http://www.wellcome.ac.uk/News/Media-office/Press-releases/2013/WTP052844.htm
Facebook: https://www.facebook.com/ClinicalTrialsType1Diabetes
Twitter: https://twitter.com/t1diabetestrial
WHO Registration: http://www.controlled-trials.com/ISRCTN27852285/
US Registration: http://www.clinicaltrials.gov/ct2/show/NCT01827735
Wikipedia on IL-2: http://en.wikipedia.org/wiki/Interleukin_2
I also think it is important to remember that IL-2 has been tested in humans twice before, and has failed both times. I previously blogged on those trials:
http://cureresearch4type1diabetes.blogspot.com/search/label/IL-2
Clinical Trial Records:
http://www.clinicaltrials.gov/ct2/show/NCT00336674
http://www.clinicaltrials.gov/ct2/show/NCT00525889
DiaPep 277's Results from an Extended Phase-III Trial:
No Longer a Cure?
I've been following DiaPep 277 for as long as I've been following type-1 diabetes cures. When I started, it was already in phase-II trials. Recently Andromeda Biotech Ltd, the company developing it, has published some phase-III results, and (most recently) some extended phase-III results. These extended results are from people who were in the phase-III trial for two years, and then continued with the treatment for an additional two years. The two year extension was "open label", meaning that the patients and doctors knew they were getting the treatment; it was not blinded.
Unfortunately, the results are decidedly mild. People's A1C numbers dropped by 0.6 (from an average of 7.6 to an average of 7.0. In terms of improvement of treatment, that's not bad. I think there is a market for a drug that would lower A1C numbers that amount, but it is not a cure. There is always hope that future improvements in the treatment will lead to even better A1C improvements (which I think is likely), or even improvements so great they lead to a cure (which I think is very unlikely). But currently, this is an adjunct treatment, not a cure. So I expect to stop covering DiaPep 277, unless I see results much larger than are seen here.
news: http://www.globenewswire.com/news-release/2013/06/05/552188/10035325/en/Andromeda-Announces-the-Results-of-an-Extension-to-Its-Phase-III-Study.html
The previously announced results from one of their phase-III trials, which I blogged about here:
http://cureresearch4type1diabetes.blogspot.com/2011/11/andromedas-diapep277-succeeds-in-phase.html
were similarly mild, and much more like a treatment than like a cure.
Phase-I Trial Resets the Immune System in MS Patients
This news comes from a human trial in multiple sclerosis (MS) patients. Basically, researchers were able to "reset" the body's immune system, to lower the autoimmunity reaction (the body's attacking it's own cells) by 50%.-75%. This was in a 9 person phase-I trial in Germany.
To understand why that is important, a little background is needed. Most researchers believe that MS and Type-1 are related diseases. In both cases the immune system mistakenly attacks the body's own cells. In Type-1, it attacks beta cells in the pancreas, and in MS it attacks the myelin sheaths of nerve cells, however the underlying autoimmunity reaction is similar.
Prior to testing on people, this method was tested in mice who had MS and in mice who had type-1 diabetes, and worked on both groups of mice. However, the human trials were MS only. But obviously, trials in type-1 diabetic people could be done as well. In my opinion, should be done.
The idea of resetting (or rebooting) the body's immune system has been tried on type-1 diabetics, and it was successful. Some of the treated type-1 diabetics did not have to inject insulin for years afterwards. However, the risk involved is high enough, that these treatments have never moved forward. At least three different teams (in Brazil, Poland, and China) have run similar trials and gotten similar results. I have blogged about them before:
http://cureresearch4type1diabetes.blogspot.com/search/label/Burt
Although it is hard to draw a direct comparison, it sounds like the procedure being tested here is much safer, but slightly less effective than the procedure used by Burt, Snarski, Li, etc. Of course, it might be refined over time to make it more effective or safer, or both.
news: http://scienceblog.com/63715/big-multiple-sclerosis-breakthrough/
Personal Note
In the past, I've posted on my blog what I call a "non-conflict of interest statement" which is this:
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 daughter has type-1 diabetes and participates in clinical trials. 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/
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