/---> causes --> beta cells to die
\---> causes --> inflammation
However, some researchers believe that the underlying immune problem causes inflammation, and that this inflammation kills the beta cells, which then causes the symptoms of type-1:
Autoimmunity -causes-> inflammation -causes-> beta cells to die
The difference is that, in the second model, if you stop the inflammation you can stop the symptoms of type-1 diabetes (the high BG numbers and the low numbers). And that is a big difference. But this second model is still a minority opinion.
OmniBio Starts a Phase-I Trial on Established Type-1 Diabetics and Expands their Honeymoon Phase-I Trial
Alpha-1 Antitrypsin (AAT) is an anti-inflammatory drug, which the body makes naturally, and which is already FDA approved for people who have a rare condition where a person don't make enough of it on their own. OmniBio had already started a phase-I trial for honeymoon diabetics, however they are now expanding in two important ways:
First, they are starting up a non-honeymoon phase-I clinical trial. Obviously, this is very important to the majority of type-1 diabetics who have had the disease for a long time:
The initiation of a late stage Type 1 diabetes trial. Proposed Trial Site: University of Basel, University Hospital-Basel, Basel, Switzerland. Principal Investigator, Dr. Marc Donath, Professor of Endocrinology, Head of Clinic of Endocrinology, Diabetes & Metabolism.Second, they are expanding their Honeymoon phase-I trial to 50 patients. At that size, it really more of a phase-II trial. Here is that part of the announcement:
The trial ... has seen improvement in the condition of the first enrolled patients. Based on observations of the first enrolled patients..., Omni Bio intends to expand the patient enrollment to 50 patients, which may involve obtaining a second trial site.That sounds like great news, but I'm very interesting in exactly what those results where. (This is a case where "details matter" and a vague statement of improvement is not good enough by itself.) Hopefully these guys will publish some details, soon.
Press release: http://www.prnewswire.com/news-releases/omni-bio-pharmaceutical-intends-to-expand-type-1-diabetes-trial-to-50-patients-117053528.html
clinical trials: http://www.clinicaltrials.gov/ct2/show/NCT01183468 http://www.clinicaltrials.gov/ct2/show/NCT01183455
Thanks to Cameron Donahue (who works with OmniBio) for providing some of the information used here.
Kamada Starts Paperwork for a Phase-I Trial of AAT
Kamada is a different pharmaceutical company that makes AAT. They currently make an FDA and EMEA approved formulation which is used for people who naturally don't produced enough AAT of their own. They are also working on an inhaled version of AAT, since the current product is intravenous, but that is still in clinical trials. They are planning to test a different brand name of AAT (Glassia®), than Omni's (Aralast NP), but I don't think that is important.
The trial they are planning includes 24 people and will be completed around December 2012. There will be no control (or "placebo") group, but three groups will each get different Glassia doses. The primary outcome for this study is general safety, and the secondary outcomes are efficacy as measured by injected insulin and A1c numbers. (There is also a mention of testing for "Pancreatic beta cell function" which I hope means C-peptide measurements, but the paperwork is not specific.)
This clinical trial is being done at two sites in Israel: Schneider Children's Medical Center (Petach Tikva) and Assaf Haroffeh Medical Center (Zerifin). Contact is Mariana Rachmiel and her phone number is +972-8-9542007.
clinical trial: http://www.clinicaltrials.gov/ct2/show/NCT01304537
corporate site: http://www.kamada.com/
Personal Opinions on the Impact of this Research on Dr. Faustman's Research
The Alpha-1 Antitrypsin (AAT) research described above may also have huge impact on Dr. Faustman's research. It could provide strong evidence that her theory is right or wrong. Dr. Faustman's theory is that BCG will cause the body to generate more TNF which in turn will kill the autoreactive ("bad") T-cells and result in the body generating more of it's own insulin. She announced that her phase-I trial had finished almost a year ago, but has not published results as yet. (A very bad sign in itself.) However, taking AAT lowers the amount of TNF in a person. This is the opposite of BCG. Especially for a honeymoon diabetic, this means that if Dr. Faustman's theory is correct, then giving AAT will cause a shorter honeymoon, and will generally result in a quicker onset and the body to generate less insulin.
So, if AAT results in a longer, stronger honeymoon, that suggests that Dr. Faustman's theory is wrong, even if she never publishes the results of her own clinical trail. Conversely, if AAT results in a shorter, weaker honeymoon, that supports her theory. Again, independent of her own results.
Teplizumab Starts Phase-II to Prevent Type 1 Diabetes
Teplizumab was being developed by MacroGenics until late last year, when it failed it's phase-III clinical trials for honeymoon type 1 diabetics. It is similar to Tolerx's Otelixizumab which also failed it's phase-III clinical trials. Both target a specific type of cell in the immune system, called a CD3. However, months before the phase-III trial failed, the paperwork had started on a clinical trial to give this drug to people at high risk for type-1 diabetes, but who had not yet come down with the disease. These patients would be identified by having two or more auto-antibodies, a first degree relative with type-1, and already having an abnormal glucose tolerance test. The idea would be to give these guys Teplizumab to see if it prevented or delayed or lessened the impact of type-1 diabetes. TrialNet is moving forward with this clinical trial.
It is easier to have a good effect on type-1 diabetics during the honeymoon phase than later on, after the disease is long established, so it makes sense that it should be easier still to prevent type-1 entirely than to treat it in the honeymoon phase. So even though this drug did not improve honeymoon diabetics, there is still hope that it might still prevent the disease.
The study will enroll about 170 people, from many different clinical sites all over the US (for the locals: UCSF and Stanford are recruiting, but nothing in Sacramento). Results in January 2016 if all goes according to plan. Since the drug has already been through phase-I and II trials for honeymooners, they can start off at phase-II for their prevention trial. If you're interested there is a recruiting web site and a lot of contact information in the clinical trial record (links below).
Recruiting web site: http://www.diabetestrialnet.org/studies/ACD3.htm
Clinical Trial: http://www.clinicaltrials.gov/ct2/show/NCT01030861
Note that the news article uses the term "Body Reboot" in it's title. I think this is a poor choice of words. The drug being tested does not reboot anything (in my opinion). I think the term "reboot" is properly used to describe the cure being researched by Burt (and collaborators) in Brazil and Snarski in Poland.
(If this had been nearer to Halloween or nearer to April 1st, my lead paragraph would have been something like this:
Zombie Drug, Left for Dead, Walks Again!Teplizumab which was last seen buried in a shallow grave, after having failed phase-III testing in honeymoon diabetics, has risen from the grave and is shambling towards a different use: preventing type-1 diabetes when given to at-risk people who have not yet been diagnosed with the disease. It was heard mumbling to itself "Hungry for Ceeee Deeee Threees. Must have Ceeee Deeeee Threees. Give meeeee Ceee Deeee Threeees...... :-)
A Little Commentary
In addition to seeing if Teplizumab can prevent or minimize type-1 diabetes, this trial will also have a synergistic effect with TrialNet’s Natural History Study trial. That trial tests relatives of type-1 diabetics for antibodies to help gather pre-diagnosis data on the disease. I know some people don't participate, because even if they turn up positive for one or more antibodies, nothing can be done. And they'd rather not know, if nothing can be done. But now, something can be done: they can enroll in this Teplizumab trial, and maybe (emphasis on "maybe") get a benefit if the trial is successful. So I think the very existence of this Teplizumab trial will help populate the Natural History Study trial. And if you have not participated in TrialNet’s Natural History Study, because you didn't think you could use what you learned, well now maybe you can.
Also, this trial simply could not be run without something like TrialNet’s Natural History Study trial. The Teplizumab study is dependent on identifying a large group of people who don't yet have type-1, but have a high chance of having the initial onset in the next few years. That's exactly the type of data that the Natural History Study produces. Without a trial like Natural History Study it is almost impossible to even test a type-1 preventative drug, because you would need to give it to thousands of people, to even see even 10 or 20 people who would eventually become type-1 diabetic. By starting with the Natural History Study data, you can run reasonably sized preventative trials, like the 170 for this one.
So this trial helps TrialNet’s Natural History Study, and TrialNet’s Natural History Study helps this trial. I would expect that as we get more and more data from the Natural History Study these sorts of follow on, prevention studies will be come easier and easy to run (and cheaper), and therefor more common.
Obviously, this trial is not research aimed at curing type-1 diabetes; it is aimed at preventing it. So I'm not sure I will continue to follow this in the future. I do include honeymoon trials. Should I include prevention trials?
Non-Type-1 Diabetes News (Learning from Other's Mistakes)
One of the major points I try to make in this blog, is that you can not make your medical decisions based on one study. No matter how good, how important, how famous, or how much you like the results. You must look at the whole area of research, and especially follow up studies, before you make a decision. The Chronic Fatigue Syndrome community is learning this lesson the hard way, as a purported connection between a retrovirus (XMRV) and their disease is coming apart in a very painful and political way:
This quote is from the editorial:
Our story today is about the danger of putting too much stock in one study and forgetting that scientific knowledge is hard won, proven over time, and borne out through many, many studies -- not just one.
Reminder About The Blog
There three ways you can help with this blog:
First, tell other people about it! Heartfelt testimonials are the best advertising.
Second, tell me about any clinical trials you know about that are not already covered here.
Third, ask me questions that you have. This tells me what I'm not explaining well, and where I need to put more information into my posts.
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF or JDCA news, views, policies or opinions.
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