Twice in the past month, my blood sugars dropped down into the hypoglycemia levels to the point where I needed two doses of glucagon.
Actually, this was by choice. These induced hypos were part of a clinical study investigating a new type of glucagon that would be a lot different than what we have now. Instead of a multi-step process requiring a complex mixing of powder and liquid -- in the middle of a hypo emergency! -- this novel product would be a one-step solution. You'll just stick the tube into a nostril and press the bottom, making the dry powder glucagon shoot into your nose where it's absorbed into the system. It's kind of like Flonase spray, except it's dry and not a mist.
There's a lot of novel work happening in the diabetes research world on new types of glucagon, from Epi-Pen delivery devices to work on stable forms that could be used in infusion pumps along with insulin -- and most recently we've heard about the exciting news from Texas-based Xeris Pharmaceuticals, testing its investigational stable liquid glucagon in the first adult type 1 PWD by way of an OmniPod!
The nasal doser, known in its investigational status as AMG504-1, fits in the palm of your hand and is very simple to use. It has a small "plunger" on the bottom that you just press to release the powder glucagon up one of our nostrils. There's a semi-loud click, and the glucagon gets absorbed into the nose without any extra sniffing needed (since it's designed for those who may be having severe hypos and could be passed out or uncooperative).
I was fortunate to be involved in the clinical trial conducted recently at Indiana University Health Research Center, one of several locations spread throughout the U.S. testing and comparing this nasal glucagon with regular injected glucagon made by Novo.
The T1D Exchange Clinic Registry is coordinating all the participating research centers in Indiana, the Barbara Davis Center for Diabetes in Colorado, Yale University in Connecticut, the University of Florida, Joslin Diabetes Center in Boston, the University of Massachusetts, University of Minnesota, UPA Buffalo, Oregon Health and Science University, and the University of Pennsylvania.
The sponsor company AMG Medical Inc. is based in Montreal and makes and distributes diabetes and other medical care supplies. A spinoff Montreal company called Locemia Solutions will be handling this product, and its co-founder and president Claude Piche is the key mind behind this nasal glucagon concept.
An estimated 82 patients are being enrolled overall in this study I was a part of (so ClincialTrials.gov tells me), and I was one of 12 adults and 10 kids to participate locally. The kids were part of an earlier arm of the study. Those conducting the clinical trial here told me the younger kids ages 4-7 only had one IV used to draw blood, and could keep their insulin pumps on to keep the insulin flowing -- unlike the older kids and us adults, who had an IV inserted into both arms for the purposes of both blood draw and insulin dosing.
These late-stage Phase III trials began recruiting in November and are designed to continue through May, though I was told that the sponsoring company AMG Medical Inc. wants to get the data prepared prior to the American Diabetes Association's Scientific Sessions in June.
Pediatric endo Dr. Linda DeMeglio is overseeing the study here in Indiana, and I heard about it through a friend in the local D-Community; fascinated, I quickly signed up for our study that began recruiting in February!
Going Low and Getting Gluc'd
My participation took the form of three clinical visits -- one screening and two separate clinic visits where I got glucagon. Both glucagon-dosing times my blood sugars were in the mid-200s to begin with, and they bolused me an incredible 10-11 units per hour (!) to drop my BG level quickly. It actually took about two hours to get my blood sugar down to about 70 where they would start closely monitoring my levels and prepping for glucagon.
And then, once I hit the 50 mg/dL mark, it was time to get the glucagon dose!
It's a randomized trial, so no one knew beforehand which glucagon type they would get that day -- traditional, or the new nasal stuff. Turns out my first visit in mid-March was a regular Novo glucagon injection, and I had to wait for the nose-puffer until the second visit in mid-April.
Once my turn came, the little tube was inserted up my left nostril and the loud click triggered the powdered glucagon. It felt almost like a bit of pool chlorine was shot up into my nose. As a former high school swimmer, that's the first sensation I felt sitting there on the hospital bed. My eyes watered slightly and there was a slight bitter taste in my mouth that caused me to cough once following the puff, but that was about it. It was overall a pleasant and interesting experience, and honestly I felt like the nasal glucagon started working in my system within a few minutes -- quicker than the normal glucagon I'd used a month earlier. Within 15 minutes, all of that sensation had passed and my blood sugars were already on the way up from the low 40s.
Oddly, the first time I was hypo unaware and really didn't feel my low, at least not until about five minutes after the regular glucagon injection. But in the second session, I started feeling the signs when I hit 70 mg/dL and then was "a little off" while dropping into the mid 40s, if you know what I mean. After being dosed with the nasal stuff, my blood sugars shot up into the high 200s later in the day, and I was wicked tired thanks to the glucoaster effect, but there weren't any other effects that I've heard other diabetics talk about with glucagon injections -- nausea, vomiting, and so on.
After the nose-puff, I did find myself sneezing a good amount later in the afternoon and even the next day, but honestly I think that's more related to seasonal allergies than the glucagon. I did mention this to the researchers, wondering if there might be any issues relating to allergies or even nose bleeds... that's something they are looking at carefully, I'm told. They also told me that each glucagon puffer is sent back to the study sponsor, because they want to test each one to see if all of the dry powder was actually dispensed into the nose. Interesting.
To gauge my reactions to both types of glucagon, the lab coordinator asked a long list of questions about any symptoms or possible side effects during the process -- ranging from classic hypo signs to any irritation in the eyes, nose, or body temperature. And then I had to stay for observation for 90 minutes after the glucagon doses each time.
Both times, I also had my Dexcom G4 CGM connected so Dr. DeMeglio kept track of my sensor readings along with using the clinically-accurate gold standard machines there in the room. It was interesting to see how my G4 was about 15 minutes behind the clinical glucose readings, except when I got down into the below 100 mg/dL range, where it was pretty spot-on. Nice!
Of course, once the glucagon got dosed both times my G4 freaked out and couldn't figure out what was happening!
For those interested, I was doing some live-tweeting during my clinical trial experiences, which can be found searching the hashtag #GlucagonTrialStudy.
Since I was a part of this clinical study and wanted to distance myself from the commercial sponsors, Amy reached out to AMG Medical's board chairman Robert Oringer, a D-Dad who's been involved in this industry for years. He was pretty tight-lipped about the nasal glucagon product that may eventually go to market, but said that it is significantly different from other soluble glucagon efforts -- like those that Ed Damiano and Steven Russell are using in their bionic pancreas trials. The nasal option is for quick emergency response, whereas the pump-specific Xeris formulation and other stable liquid forms would eventually allow a full-fledged closed-loop, in which glucagon can be administered alongside insulin as needed.
One of the aspects mentioned was the notion of non-responders, i.e. some people for whom the initial emergency dose is not effective. This is apparently quite common, so much so that EpiPens are sold in dual-packs to counter this, for example, Oringer says. And it's possible that some folks won't respond to the first dose of nasal glucagon either, and may need a second one.
The nasal glucagon is obviously aimed at not only taking away the anxiety of an injection, but also the confusion that can come from having to perform a nine-step liquid-and-powder mixing process at the very moment you're experiencing an emergency situation. Not only would simplification be helpful on the homefront or out in public, but it would also be a huge benefit for school or workplace situations.
To that end, Oringer tells us they're preparing a second study that will look at human factors, i.e. not just the effectiveness of the glucagon dose but also comparing how caregivers are trained and able to use the nasal unit versus the traditional glucagon kit. The critical point is to look at the product in the hands of people who'll use it in real-life situations, and explore their rate of success. Don't forget: it's not generally the person with diabetes administering the glucagon, but some poor soul -- family member or otherwise -- struggling to help in an emergency.
He also says AMG Medical is hoping to get priority FDA review, which would save four to six months, but the exact timeline for submission is not yet clear.
Having tried it myself, I think this type of nose-puff glucagon could be a beautiful thing -- even better than the EpiPen-style glucagon under development (which still does involve an injection). This nasal form could take away a lot of the fear and loathing associated the need for glucagon in emergency moments.
In short, I am a fan of it, and look forward to seeing how this product fares as we move forward in this intriguing race to make glucagon more user-friendly.
** Feb. 18, 2015 UPDATE** Very exciting to see the clinical data from this study being presented at the Advanced Technologies and Treatments of Diabetes (ATTD) conference in Paris. This post from T1D Exchange has more detail.