This clinical trial is studying people who were part of ViaCyte's clinical trial of VC-01™, an encapsulated beta cell cure. Once the device is removed at the end of the study, the patients can enroll in this follow on study which tracks them for three additional years, looking for adverse effects.
ViaCyte is a commercial company testing an encapsulated beta cell cure. You can read my previous blogging about them here: http://cureresearch4type1diabetes.blogspot.com/search/label/ViaCyte
They are in the middle of a large Phase-I study, which could finish as early as 2020.
Clinical record: https://clinicaltrials.gov/ct2/show/NCT02939118
Discussion
I'm hopeful that this means that one person has finished the ViaCyte protocol, which is motivating them to start this follow on. The other option is that they are just planning ahead. Since there is no control group, the interim data could be published, if ViaCyte wanted.
Two Phase-I Studies Start with Umbilical Cord Treg Cells
These two studies have a lot in common, so I'm going to discuss them together: first, their similarities, then their differences. Here are the similarities:
- They are both run by the same researcher (Dr. Zhiguang Zhou) at the same hospital (Second Xiangya Hospital of Central South University).
- They recruit at the same place: Institute of Metabolism and Endocrinology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China, 410011
Contact: Zhiguang Zhou, MD/PhD 86-731-85292154 zhouzg@hotmail.com - They have already started recruiting 40 people, and expect to finish in 2019.
- These trials are open to people who have been diagnosed within 3 years and are between 6 and 60 years old.
- Each has a primary end point which is safety related, and secondary endpoints which are effectiveness related and include C-peptide, A1c, insulin usage, etc.
- Both studies will work with stem cells which have been harvested from umbilical blood, separated into components, and had the T-reg cells "grown out" for two weeks. These enriched T-reg cells will be infused into patients. T-reg cells are regulatory cells which are part of the immune system, and work by controlling other immune cells so that those other cells don't attack beta cells.
The first study is Safety Study and Therapeutic Effects of Umbilical Cord Blood Treg on Autoimmune Diabetes: This study will have two groups, one will get the treatment, and one will be a control group and will not get the treatment.
Clinical trial registry: https://clinicaltrials.gov/ct2/show/NCT02932826
The second study is Safety and Efficacy of Umbilical Cord Blood Regulatory T Cells Plus Liraglutide on Autoimmune Diabetes: This study has four groups. One will get the treatment and also Liraglutide, another just the treatment, a third just Liraglutide, and a fourth will be a control group. Liraglutide (sold as Victoza) is similar to exenatide (Byetta), which is a common type-2 medication, but is also sometimes used on type-1. Victoza is a weekly injection.
Clinical trial registry: https://clinicaltrials.gov/ct2/show/NCT03011021
Discussion
The researchers are not clear on why they are using Liraglutide, but site its "various benefits for beta cells". They expect it will increase the effectiveness of the new T-regs, possibly by encouraging beta cell growth.
JDCA's Update on Dr. Faustman's Research
An update on Dr. Faustman's BCG research by the JDCA (Juvenile Diabetes Cure Alliance) is here:
http://eepurl.com/cHrGqX
My key takeaway points are:
* The Phase-II trial should finish in 2023.
* They have enrolled 125 out of the 150 they need.
* An 8 year follow up from their Phase-I trial should be published by the end of 2017.
(Remember, I am a fellow of the JDCA and we regularly discuss various research programs, including this one.)
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.
7 comments:
Josh, I have never held much promise in Dr. Faustman's research, but I hope someday I am proved very wrong. I see little to come from Dr. Zhou's research. I am extremely hopeful however for the ViaCyte research. Who knows one of three isn't bad by any standard. Especially among us naysayers in Indiana. :)
At the end of the day, it does not matter how many research projects fail. It only matters that one succeeds. --Joshua
There are three problems with manipulations of the immune system to stop the auto-immune assault on the pancreatic beta cells. First, the immune system is extremely complex and dynamic in its internal interactions, so any interference with it may have unpredictable effects, such as unleashing other autoimmune responses, like multiple sclerosis, for example, which is already more common in type 1 diabetics than in the normal population. Second, suppressions of the immune system are usually toxic, and greatly increase the risk of cancer and infections. And third, even after the autoimmune attack on the beta cells is stopped, they don't spontaneously regenerate, but some additional substance, such as the INGAP peptide, is required to stimulate them to regrow. Unfortunately, so far all these interventions have stimulated too little additional beta cell function to make much difference. So I think this approach, which has been going on since the cyclosporine experiments of the mid-1980s, is simply too complex and slow to be worthwhile, except for very newly diagnosed patients, for whom immunosuppression may preserve some residual beta cell function.
That said, small improvements in beta cell function can have important clinical effects on the patient, such as greatly reducing the risk of potentially lethal hypoglycemia and making blood sugar control easier, thanks to the support provided by even a little insulin output naturally tailored to the body's requirements. Studies of long-term survivors with type 1 diabetes show that they have higher residual production of insulin than those who don't survive as long, suggesting that the degree of blood sugar control that can be achieved depends on how much innate insulin production remains after the initial autoimmune attack.
Overall, the most rapid and simple approach to a functional cure for type 1 diabetes would be to develop an adequately productive beta cell capsule, since all the complexities of immunosuppression and beta cell regrowth would be circumvented. The remaining problem there is that these capsules quickly become ineffective because of insufficient oxygen supply, so this should be the focus of efforts now.
I do agree with your first two paragraphs. However, I think you are wrong to phrase your third paragraph as though you are stating facts. That third paragraph is your opinion. There is some data that supports it, but there is some that does not. But the bottom line is that no one knows with certainty that there is only one problem remaining before encapsulation is a cure, much less that we know exactly what that one problem is.
Joshua
Beta cells have been proven to regenerate both in vitro and in vivo under the right conditions.
Not only from drugs, but also through fasting. See Dr Longo's FMD. It's also easy to suppress your immune system without drugs, this is what occurs naturally when fasting, and has been done to regenerate the awful effects of chemotherapy in cancer patients for a while now to great effect (on survival).
In my opinion, the cure to type 1 diabetes will involve fixing our gut microbiome somehow. Resveratrol / metformin has also been shown to promote microbial growth to line the lower intestine and this reduces inflammation. Also, it's also now theorized that type 1 isn't an auto-immune disease per se, that the immune system is functioning as it should but that stressed beta cells can produce "nonsense proteins" and that it is these proteins triggering the (from one point of view, appropriate) immune attack.
https://www.sciencedaily.com/releases/2017/03/170327131210.htm
The specialised diet developed by CSIRO and Monash University researchers uses starches -- found in many foods including fruit and vegetables -- that resist digestion and pass through to the colon or large bowel where they are broken down by microbiota (gut bacteria). This process of fermentation produces acetate and butyrate which, when combined, provided complete protection against type 1 diabetes.
"The Western diet affects our gut microbiota and the production of these short-chain fatty acids," researcher Dr Eliana Mariño said.
"Our research found that eating a diet which encourages the gut bacteria that produce high levels of acetate or butyrate improves the integrity of the gut lining, which reduces pro-inflammatory factors and promote immune tolerance," Dr Mariño said.
"We found this had an enormous impact on the development of type 1 diabetes," she said.
Paper here:
http://www.nature.com/ni/journal/vaop/ncurrent/pdf/ni.3713.pdf
In the absence of a full cure, it's also promising that home c-peptide test kits are being developed now, a few years off, which will greatly help people figuring out what affects their c-peptides which rise and fall over the lifespan of a type 1 diabetic, for various reasons. Many have experienced mini-honeymoons and figuring out exactly what causes them will help narrow the search.
I think the most promising temp-fix drug for type 1s will be smart insulin, and has a good chance of being commercialized because it's not a permanent cure so the profit motive is strong to produce a successor to insulin which allows you to skip testing your blood sugars or even worrying about it at all. Especially, not having hypos.
Of course I'm all in favor of saliva based or sweat based continuous glucose monitoring. My poor fingers.
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