- Last week, we visited Drs. Ed Damiano and Steven Russell to discuss their use of the bionic pancreas at a summer camp. This report includes an update of that study plus a Q&A with the participants and staff.
- The campers repeatedly said the bionic pancreas provides them with superb glucose control while allowing them to forget about their diabetes.
- The biggest challenges in the study have been the infusion/CGM sites “sweating off” and device communication issues (i.e., remote monitoring, cellular reception, Bluetooth connectivity).
Last week, we attended Camp Joslin and Camp Clara Barton, the Joslin Clinic’s long-running camps for children with diabetes. There, we saw Drs. Ed Damiano and Steven Russell conduct their summer camp study for their bionic pancreas. Eight kids at a time wore the bionic pancreas –, two Tandem t:slim pumps (insulin and glucagon), a Dexcom G4 Platinum sensor and transmitter, and an iPhone 4S controller. The kids did this for five days and went about their usual camp activities. Thirty-two children enrolled (12-20 years old), 16 at Joslin and 16 at Clara Barton; each patient served as his or her own control, meaning five days of usual care at camp compared to five days of closed-loop control wearing the bionic pancreas.
The study was notable in that it has tested the bionic pancreas in a very real-world outpatient setting in adolescents with diabetes – an age group that tends to have the highest A1c’s and the most challenging time with glycemic control. It’s also key to note that campers are not really restricted in their activities – they play sports, take part in usual camp festivities, eat as they please, and sleep in cabins with their peers. While the level of monitoring is obviously high to ensure safety, it takes place from a distance and is not intrusive – a remote monitoring center and a few nurses help ensure things are running safely and smoothly. The size of the study is also quite notable – the 32 participants have allowed the team to amass 4,320 hours of closed-loop control. Last, there are no IV lines or highly invasive blood glucose monitoring. Rather, the team is using point-of-care HemoCue meters and CGM to assess outcomes, a big step from previous studies that relied on the bedside GlucoScout device.
To see some pictures from our trip, see below or visit http://close.cx/BionicPancreasCampPictures. This report is a follow-up to Kelly’s participation in the Beacon Hill study last spring (see http://www.diatribe.org/issues/55/test-drive).
- “My goal is to have you think about diabetes as little as possible,” Dr. Damiano told the campers at the start of the study. By far, the participants said the best parts of the bionic pancreas were that it provides them with outstanding glucose control while allowing them to forget about the disease. We would note that historically, this combination has not been possible in practice – new therapies and technologies for type 1 diabetes have typically increased the burden of therapy on patients and providers (at least from an educational perspective, including SMBG, pumps, and CGM). Indeed, Dr. Russell characterized the insulin pump and CGM as the platform, and the bionic pancreas’ algorithm as “the ultimate app.” Thus, when takingoff the bionic pancreas at the end of the study, Dr. Russell succinctly described the reaction of most participants: “Vacation is over.”
- Dr. Russell noted that the view of the trial as a “vacation” underscores how challenging type 1 diabetes can be. He said that for most people without type 1, participating in one of the bionic pancreas trials would be a pretty crummy vacation indeed, as these individuals are undergoing multiple fingersticks (with a clunky HemoCue no less!) for data collection. They are also being tracked down by a nurse in case the remote monitoring uplink needs to be refreshed, have two daily site changes (insulin and glucagon), get blood glucose checks in the middle of the night, etc.
- Overall, the participants’ enthusiasm was off the charts – “Awesome” was the most common answer to our question, “How do you like the bionic pancreas?” Almost every patient we talked to would wear one if the current version were commercialized right now, despite a fair amount of burden wearing two Tandem t:slim pumps and carrying the iPhone controller/G4 Platinum receiver. This is, of course, an investigational device (see below) and there are still imperfections that need to be ironed out.
- Most participants told us their blood glucose averaged 100-140 mg/dl on the bionic pancreas, with very little hypoglycemia. For almost all patients, this represented a noticeable and welcome improvement over their current standard of care – and these are virtually all patients that are being seen at the Joslin Clinic! Most of these patients were well controlled to start, and most were already pumpers and/or CGM users at home, so it is not to be taken lightly that participants saw a significant improvement in glucose control. The system’s algorithm learns more about each patient over time and improves its performance, so days three through five tended to be much better than days one and two, according to the researchers.
- The first big challenge for Drs. Damiano and Russell this summer has been sensors/pump infusion sites coming off – this comes from a combination of the high level of activity, and in the case of the Clara Barton camp experiments, sweat from 100-degree heat. Through trial and error (and Amazon reviews!), Dr. Russell and the participants have become fans of kinesiology tape (e.g., KT Tape, Rock Tape) for holding sensors and sites in place – it has the right combination of stickiness, flexibility, and waterproof qualities, they emphasized.
- The second major challenge this summer has been device communication problems–spotty cellular service in the camp’s remote, wooded location. Cellular communication wasn’t required for the function of the bionic pancreas, but it was used for remote monitoring so that the researchers could track the device. The cellular and connectivity problems were solved with a 4G MiFi portable hotspot, though Drs. Damiano and Russell briefly considered buying a generator-powered portable cellular tower!
- Most noticeable to us were the nuisances/finicky-ness of Bluetooth connection between the t:slim pumps and the iPhone. One of the first things we heard a nurse say after we arrived was, “I think C-01 walked away from his pancreas. His CGM is not reading and he is double unpaired.” Each pump has to be “paired” with the iPhone, and when patients leave the bionic pancreas controller out of range (e.g., leaving it in the cabin), the two pumps must be “re-paired” by a nurse. This was pretty quickly noticed at the remote monitoring center, and a nurse was sent out to find the camper and re-pair the pumps. The envisioned final device won’t depend on wireless communication with pumps, so these are temporary problems associated with the research-only device.
- The problem of device connectivity echoed comments from researchers at April’s FDA/NIH/JDRF Workshop on Innovation Towards an Artificial Pancreas. At the time, Dr. Boris Kovatchev (University of Virginia, Charlottesville, VA) called inter-device communication the “weakest link” in the closed loop. For more, see page two of our report at http://www.closeconcerns.com/knowledgebase/r/9f3e2601.
- “They are brutal on this equipment.” This is as real world of an artificial pancreas study as we’ve seen to date. Participants take part in all camp activities, including swimming (though they must reconnect every 30 minutes). Dr. Russell mentioned kids aggressively belly flopping and sliding on wet grass laced with rocks – one camper needed stitches! One camper apparently dropped his bionic pancreas control unit between two cinderblock walls next to the shower. The controller kept reading his CGM, controlling his pumps wirelessly, and regulating his blood glucose through the wall, though it took a squeegee attached to a coat hanger to fish it out. See https://closeconcerns.box.com/s/jad9j5i1bfrkoxd6qea9 for a picture of Drs. Damiano and Russell examining the wall where this happened.
- When the CGM signal drops out, the system reverts to basal rate, calculated as the average of that five-minute segment over the past seven days. In short, a really personalized basal rate that can adapt to changes in insulin sensitivity over time. Put more simply, much better than the current standard of care best-case scenario: doing a fasting basal test, tweaking one’s basal rate, then doing another fasting basal test to confirm the change was effective.
- Some participants were not on CGM prior to the study, though they were strongly considering it (or had already gotten it) after taking part in the closed-loop experiment. Some mentioned that they previously thought CGM would be inaccurate or not that useful – this reinforced challenges with current CGM: The technology has improved enormously, but some recall generations from long ago. While not all were sold on CGM after the study (one patient was happy to check his blood glucose many more times per day instead of carrying the receiver around), the experience of wearing real-time CGM really improved the user experience and showed us how valuable CGM will be the closer that the field comes to “open loop” approvals. We also think this speaks to the importance of risk-free trials – deciding to go on a new technology like a pump or CGM is a huge decision, and the opportunity to try before you buy would be positive for many – though admittedly, not everyone would necessarily want to try it without the bionic pancreas algorithms – yet!
- Drs. Damiano and Russell believe that several participants are still producing insulin based on their very good open loop control. Unlike the Beacon Hill study, the camp studies do not exclude patients based on detectable levels of C-peptide. This seems like a move in the right direction, since some people with type 1 diabetes still produce some insulin. Overall, these patients likely have better open-loop results than one might expect, though their closed-loop control will almost certainly have fewer hypoglycemic episodes and shorter periods of post-prandial hyperglycemia.
- The placebo-adjusted outcomes might underestimate the bionic pancreas’ impact, since the control groups (both the open-loop phase and the standard campers) appear to have better control than under standard care in the home setting. Drs. Damiano and Russell said that children at camp often have better control than they do at home (potentially one A1c point better), as they are undergoing at least seven fingersticks per day and are always taking their boluses – and are always surrounded by other children going throughexactly what they are going through. Thus, the trial’s second control group (campers not enrolled in the trial at all) likely overestimate how good glycemic control is under standard care as well. Study participants had extra blood glucose checks compared to the usual camp care, and these could result in corrections, thereby improving control. They also had different rules for treating hypoglycemia from usual camp care: study participants did not get carbohydrates when blood glucose was 70-80 mg/dl if they weren’t symptomatic; conversely, usual camp care would err on the side of intervention.
- Drs. Damiano and Russell envision the final product as a dual-chambered pump with the algorithm and CGM receiver embedded in a single device. Using such a bionic pancreas would require carrying just one device, wearing two infusion sets (glucagon and insulin), and a CGM sensor/transmitter. The biggest roadblocks in terms of wearability at this stage are twofold:
- Development of a dual-chambered pump – Tandem has a partnership with JDRF on this front, as announced in January at JP Morgan 2013; and
- Stabilized glucagon for use in a pump – Biodel, Latitude, Xeris, and Zealand are all working on this front.
- Dr. Russell reminded participants that the final device’s structure is not guaranteed. Many of the participants expressed their excitement for a future version of the bionic pancreas. In these moments, Dr. Russell explained that some aspects of the device (e.g., stabilized glucagon, a dual chamber pump) are not in his or Dr. Damiano’s complete control, and are not a guarantee if/when the first commercial version is launched.
- There was no problem enrolling the study – a single email to registered campers filled all 32 spots. As we understand it, there was a waiting list of people who wanted to get in the trial, including people who were not even registered for the camp. Patients were compensated $1,000 for participating. Kudos to Drs. Damiano and Russell for having few exclusion criteria – there was notably no C-peptide cutoff (a nice way to test the system in a broad spectrum of type 1 patients), and the only exclusion criterion was pregnancy. We aren’t surprised at all how many children’s parents were eager for them to try the system, and we suspect spots in future such trials will continue to become even more coveted.
- Fundraising has also been challenging from a time perspective. “About 20-30% of my time goes to fundraising,” said Dr. Damiano. The summer camp study has cost ~$1.2 million, with ~$700,000 coming from the Helmsley Charitable Trust and ~$500,000 coming from the NIH. The glucagon purchased for the camp study has cost ~$25,000 – two $100 Lilly glucagon kits per day per patient! Drs. Damiano and Russell, on behalf of Mass General and BU, purchased the Dexcom receivers/transmitters as well as the iPhones. Tandem donated all of the t:slim pumps for the study. The initial bionic pancreas controller cost $93,000 to develop; these funds came from private donations and the Banting Foundation.
- Drs. Damiano and Russell have an ambitious plan for upcoming studies of the bionic pancreas. See below for the upcoming slate of studies. Drs. Damiano and Russell shared the timeline with study participants cautiously – clearly, they know that many things must fall into place for the bionic pancreas to get to market in a timely way; ~ 2017 is their goal, which is when Dr. Damiano’s type 1 son will be headed to college. (he is currently 14).
Study (size, length)
Beacon Hill Study (n=20, five days)
One-to-one nursing, five days of free roaming around the Boston Peninsula centered around the Beacon Hill neighborhood. Sleeping in hotel room with venous blood glucose monitoring at night.
Finish in fall, 2013
|Exercise Study (n=12, five days)||
Testing a new feature of the
controller that incorporates exercise information
Hospital Staff Study (n=48 - pending full funding, 12 days)
|Staff sleep at home and go to work as usual; Stanford, UNC, UMass, MGH||
Throughout 2014 (two months per site, one site at a time)
Pediatric Summer Camp Study (n=24, five days)
Testing the bionic pancreas in 6-12 year olds
Pivotal Studies (n=TBD, six months)
Questions and Answers with “The Bionic Kids”
Q: What do you think of the bionic pancreas?
A: It is awesome. My blood glucose levels are around 108 all the time. My lowest has been 55, and my highest has been 220. I now feel low at a higher level.
A: I have done my diabetes management for 14 years, and this is exponentially better than I have ever done.
A: It is really cool. This is like the fifth day where I have not had to do anything for my diabetes. A: It is awesome; my numbers have been really good.
A: I love it. My blood glucose has been 130 mg/dl.
A: I have been very impressed. I had a really tough two weeks of control before starting the trial, and was not sure about it. After the first two days, though, it did a good job and really started bringing me down – and I really worked it, I had been all over the place.
A: It has been a lot better than I expected. My numbers have been incredible. They have been going down each day; I would love to see what would happen if I stayed on it for another two days. Tomorrow, they are going to tell us what our A1c would be if we stayed on the bionic pancreas – I think I would be down below 7%, since I am now getting to around 120 or 130.
A: It’s really cool. I did not have to keep thinking about my diabetes the whole time. I am really excited about getting it when it comes out in 2017.
Q: What has been the biggest challenge of being on the bionic pancreas?
A: Knowing that I was going to have to start treating lows when I gave it back.
A: It was weird being normal – not having to think about it and just having it do everything for me.
A: It was not a challenge but it was weird having my blood glucose levels go up without my doing anything. I woke up at 55 and went up to 80 by just sitting there for ten minutes.
A: Nothing; I don't mind the pumps and site changes.
A: Having all of these things to carry around and the site changes every day is a pain.
A: The two pumps and CGM – it's a lot of stuff. I ran out of room on my body to put the sites.
A: I have two pumps, and a CGM on right now, which is a nuisance. When it comes out in 2017 it won’t be like this though.
Q: What were you most concerned about entering the trial?
A: I was nervous that the glucagon would make me feel nauseous. I haven’t though because the doses are so small.
A: I was really worried about not being in control of my blood glucose levels. It was scary thinking that thing would be putting insulin or glucagon in my body during my sleep without my knowing.
A: It goes against what we are taught – we are taught from a young age to know what we are putting into our body.
A: I was freaking out; I was not sure what to expect, and I was really nervous about giving control to it.
A: I was not sure what to expect. I was really concerned about how often I would be pulled out of activities or not being able to do activities at camp. Fortunately, it has not been too bad.
A: I had heard Ed and Steve talk about the bionic pancreas at last year’s camp, so I knew about it. I was a little nervous about not being in control.
Q: If you could change anything about the bionic pancreas (add a function etc.), what would it be?
A: Not having to change the pump sites every day.
A: It is pretty clunky having two pumps and two sites. In my sci-fi head, it would be possible to give the insulin and glucagon in the same site from one pump.
A: I can’t think of anything; it is pretty great the way it is.
A: Make it waterproof! It’s hard to keep reconnecting. And smaller size. I called it my utility belt. Q: Did you wear a pump or CGM before the trial? If no, would you wear one now? A1: I was not on a CGM; I want to try and get one when I go home.
A: I wear a pump. I will get a CGM now that I see how accurate it is. I was in a previous CGM study, but it was with an earlier device.
A: I wear a t:slim normally. I’m going to get a Dexcom CGM after this study. I only have to check two times per day!
Q: If the bionic pancreas were available in its current structure (two pumps, unstable glucagon, etc.), would you buy it?
A: Absolutely. I would get it, even if it meant having to wear two pumps and a CGM, do site changes for each pump every day, and mix the glucagon each morning. I would buy it as is.
A: Yeah I would.
A: It is going to be one pump, and they are working on a glucagon suspension. If these didn't happen? I don't think I would – it’s so much stuff. But this is not the final version; in 2017 it will be a single pump. Then it’s a no brainer.
Q: Did you talk to your parents about this study?
A: Yes, they were also really nervous about my participating. A: Yes. My parents were excited about it.
-- by Adam Brown, Hannah Deming, and Kelly Close