AAT (Alpha-1 antitrypsin) Starts A Phase-I Trial
I've blogged about AAT in the past, here: http://cureresearch4type1diabetes.blogspot.com/search/label/AAT
The good news is that they (finally!) actually started their phase-I trial:
The announced that they were going to start the trial back in June, but this is the actual start of dosing for the first patient.
This 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. You can read my general comments about all inflammation based cures: http://joshualevy.pbworks.com/ConceptsAndBackground#Inflammation
Here is the clinical trial for "part 1" of the trial:
And here is the record for "part 2" of the trial:
Part 1 is 16 people and part 2 is 66. Both are honeymooner's only (within 100 days of dx). Together, they are supposed to run from Oct 2010 to Nov 2014, but I'm very hopeful that they will publish their part 1 results sooner than that. They need to do part 1, before they start part 2. However, the treatment phase will last at least 2 months, and then each patient will be followed for 2 years, so this is not going to be a quick result. Part 1 is currently only recruiting in Emory University, Atlanta, Georgia, USA. Contact: Stephanie Meisner 404-785-8136 firstname.lastname@example.org. However, they hope to recruit in many other places soon, including Barbara Davis Center; University of Colorado, Aurora, Colorado, USA, and (the only California location) University of California San Diego, La Jolla, California, USA. Based on Dr. Lewis's comments (see below) they might already be recruiting at Barbara Davis Center.
Because AAT is already approved for use in people, it could start out at as a phase-II trial or even a phase-IV trial. Both parts of this trial are labeled "phase-II" but since AAT has never been used on type-1 diabetics before, and part 1 only has 16 people, I prefer to think of part 1 as a phase-I clinical trial, and part 2 as phase-II.
In addition to all that, thanks to a anonymous but alert reader over at CWD, I can include a link to the following web with discussion by Dr. Lewis, who is deeply involved in AAT research:
Be sure to read both page 1 and page 2, and most especially Dr. Lewis's answers to the many comments. Also remember that he is covering both type-1 and type-2 in different parts of his text and helping transplants (rather than directly curing type-1) in some parts, so you need to understand the context of the question to understand his answer.
He is really positive about this. Of course, everyone should be positive about their own research. :-)
I would be particularly careful about his answer to question 9. Especially during the honeymoon phase, you might get that kind of result from luck. It's important to remember that's just one personal testimonial. It is the kind of thing that motivates a clinical trial, but not a replacement for a clinical trial. Finally, if anyone who does medical research professionally has any thoughts on his answer to question 13, I'd be interested in your opinions; especially the "AAT activity" part.
Basic summary is that they have now dosed 10 out of the planned 12 person clinical trial in New Zealand. (LCT refers to this a phase-II trial, and it is their second one, but it's also much smaller than other phase-II studies: 12 people, instead of the 50+ people that is common.) The longest follow up was for one year. The first 4 people got 10ku/kg and have been followed for 30 or more weeks, the second group of 4 got 15ku/kg and have been followed for 8 or more weeks, and the last group of 4 got 20ku/kg and are still being dosed.
The first group's average insulin needs dropped by about 30%, but no one was reported to have gone "off insulin" for any length of time. Both first and second groups had a large drop in low blood glucose episodes.
Press release: http://www.lctglobal.com/html/blob.php/LCT%20NZ%20Trial%20Update_271010.pdf?attach=0&documentCode=2264&elementId=20084
Some Discussion and Opinions
This news definitely feels like more of the same. Normally, more of the same (repeating your results) is a good thing. And it may be a good thing here, also. However I'm a little nervous that the dosage has gone up a lot: 5ku/kg to now 15ku/kg, but the results have not gotten better. (At least that I can see from their published data.) Part of that is that the early 5ku/kg guys, some of them got extra transplants. But still, whatever is happening, it does not look like simple giving more islets is going to result in big improvements. At least not in a straight forward (linear) way.
The last group from this last clinical trial got the highest dose so far: 20ku/kg, and their data has not been reported on at all. I hope that they do better than the earliest 5ku/kg group. (Meaning at least 25% go insulin free for some period of time, for example.)
El-Khatib Artificial Pancreas Update
Here is an "feel-good" article about the artificial pancreas being developed at Boston University
This is an artificial pancreas which is unique in that it can dose insulin if the person goes high, and glucagon, if the person goes low. Obviously, this gives it some interesting advantages over an AP that can only dose insulin.
This is the paragraph which summarizes where they are right now:
So far, Damiano's team has tested its algorithm in 15 people in one- to two-day experiments. The first trial, in which they tested adults for 27-hour stretches, demonstrated that safe and effective glucose control was feasible with the two-hormone artificial pancreas. In the second trial, currently underway, they are testing the system in children and adults for 51 hours and have included an exercise component. (Since exercise can lead to increased risk of hypoglycemia, this adds an additional level of challenge to the algorithm's decision-making process.) Because the trial is ongoing, the team is hesitant to draw early conclusions, but Damiano says that they are very encouraged by the results.And where they hope to be in the future:
Damiano says he hopes to be performing out-patient trials by 2012 and estimates that the device could be on the market by 2015.
There was one wrinkle to this research, which I had not known before:
One of the hitches, however, is that glucagon is not yet approved by the Food and Drug Administration for long-term use because it breaks down in solution. Several companies are tackling that problem. In the meantime, since a system that uses only insulin is likely to be FDA-approved sooner, Damiano's team is working on an insulin-only system as well.Some Discussion and Opinions
The "out patient" trials they refer to in 2012, mean wearing the AP outside of the hospital. Right now, all testing is done in a hospital. Also, I think the 2015 date for FDA approval is a little optimistic. From a regulatory point of view, they would need to do phase-II trials, phase-III trials, and get marketing approval, all within five years. (And that's separate from the scientific work of developing an AP that worked, and the engineering work of figuring out how to produce it! Nor is it counting separate approval for long term glucagon,)
I want to thank everyone over at BB for their huge outpouring of support. You guys have no idea how many emails I got; it felt wonderfully supportive.
I feel that my blog looks a little "old", so I'm going to update how it looks sometime this month. So don't be surprised if it suddenly changes it's look, and then changes again to something else! If anyone has ideas on improvements to how the blog looks, or the static text on the blog page, now would be a great time to email me or leave a comment.
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF or JDCA news, views, policies or opinions.