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:
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:
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.)
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.
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/
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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.