Even though Ed Damiano isn't living with diabetes, he occasionally wears a continuous glucose monitor and two Tandem t:slim pumps, and he constantly has his eye on all the newest D-devices.
Sometimes his pumps are filled with saline and sometimes colored water, with blue liquid representing insulin and red standing in for fast-acting glucagon. The Boston researcher is wearing the devices in the name of his 13-year old son, David, diagnosed with type 1 more than a dozen years ago. But he's also in it for the bigger diabetes community, as the diabetes devices represent the future of Damiano's work on a "bionic" artificial pancreas that's now moving into the key research period from clinical settings to the real world.
In an interview last year, we chatted with Damiano about his human clinical trial work that's a joint effort between researchers at Boston University, Harvard Medical School and Massachusetts General Hospital. The initiative is just one of several ongoing efforts across the U.S. and abroad developing and studying artificial pancreas models, and as with many involved in this kind of research, it's personal for Damiano.
He stepped into the diabetes community about 12 years ago when his wife Toby, a pediatrician, diagnosed their son at 11 months. They had no family history and didn't know anything about the autoimmune condition, but quickly learned what they needed to do for their son. With an academic background in mechanical and biomedical engineering, Damiano put his experience to use at the University of Illinois and started pondering ways to come up with a technological method to automate what D-parents and PWDs must currently do manually to control blood sugar levels. And that set the stage for the current research, which Damiano is proud and excited to now see expanding. He's working with Dr. Firas El-Khatib, senior research scientist at Boston University, and Dr. Steven Russell, a Massachusetts General Hospital endocrinologist who also works at Joslin Diabetes Center and supervises the project's clinical trials. The team is creating a prototype they call the "bionic pancreas," using a continuous glucose monitor (CGM) and two t:slim pumps insulin pumps — one containing insulin and another containing glucagon.
The CGM component is a special custom-designed device by Tandem that merges an Abbott Freestyle Navigator receiver (a now-defunct device in the U.S.) and an off-the-shelf iPhone 4 (!), enclosed together in a black plastic shell. The combo device is about as thick as three iPhones, with a screen on both the front and back sides. It even has a slot to carry test strips! A special app calculates the algorithm and communicates wirelessly to the insulin pumps, and then also sends everything to the "iCloud," where all the data can be accessed and managed. Not to worry: for this round of experiments, the cellular and texting function is turned off on the phone, so users only have access to the pancreas app and can't access other phone functions.
This current version will be used in upcoming studies, Damiano says, but his team is working with Dexcom to create an updated version that will be similar except that it will use the new Dexcom Gen4 sensor, currently under regulatory review. He hopes the new model will be ready in a month or two, since rumor has it FDA will approve the new sensor by the end of 2012.
Following the ADA Scientific Sessions this June, where he and his team presented some research findings (and Damiano wore and demonstrated the system with colored water!), they received a grant for a new study using the glucagon-filled pump — a component that makes their initiative unique among those studying the artificial pancreas concept. The idea isn't new, but it's become more feasible as glucagon has evolved and dual-chamber pumps have started being envisioned.
Damiano describes the dual-chamber pump using glucagon as being better protection against hypoglycemia than the Low-Glucose Suspend (LGS) function that's currently available in Europe but still being reviewed by FDA here in the U.S. The LGS function temporarily stops insulin delivery once a PWD reaches a programmed BG level, but Damiano says the function is too slow and someone could be hovering at dangerously low levels or even be continuously dropping as the LGS just starts to kick in. Instead, the glucagon-filled pump can respond quicker and start raising a person's BG levels by basically bolusing small amounts of the fast-acting glucagon immediately.
"It's proactive and much more effective than LGS. From a regulatory perspective, the insulin delivery doesn't change but this adds a safety net," he said. "The Achilles Heel is the danger that the sensor might not be accurate and (delivering glucagon) could push you up higher, and that really goes at the fact that the U.S. sensors we have right now aren't good enough. But that will come with time."
Damiano sees a lot of potential for a glucagon-only pump, which could be a "transitional device" that might get approved and become available for people who pump or inject insulin before any more complex artificial or bionic pancreas. A three-year study planned for sometime next year would potentially allow PWD study participants to wear the glucagon pump for 11 to 14 days, using their own insulin therapy during that time.
The next phase of bionic pancreas research will begin at the end of this year, Damiano says. The overall timeline is quite ambitious:
- At the end of 2012, a year-long study will look at the two-pump and iPhone-CGM device system being worn by roughly 20 adults for five days. Damiano plans for two PWDs (age 21 or over) to be included each month. During these studies, the participants will stay overnight in hospitals beds (with frequent blood glucose monitoring by staff) and have free run of Massachusetts General Hospital campus, with access to the fitness center for exercise, the hospital cafeteria for whatever they want to eat, and a nurse chaperone for safety during the day. Damiano also hopes four or five other hospitals across the U.S. that have been trial-running other artificial pancreas systems might agree to participate in this research too.
- Next summer and again in 2014, Damiano's team will take this research to Camp Joslin and the Clara Barton Camp in central Massachusetts. They plan to put a total of 32 pediatric PWDs ages 7-21 on the closed-loop system for two weeks this next year and an open-loop system (where the devices are not connected for automatic control) for another two weeks in 2014 for kids 6-12, monitoring the results while the campers participate in regular camp activities. Damiano says his team is pursuing an NIH grant and other opportunities to help fund that phase of research.
- If all goes according to plan, he hopes that a hospital day-study for 24 adults would follow in 2014, allowing participants to work in the hospital and sleep at home while using the system.
This is significant because it goes further than the feasibility studies the team has been doing since 2008 (which should be completed this fall), and which most other artificial pancreas projects are currently engaged in. So far, Damiano's study participants have been hooked up to the devices on the 13th floor of Massachusetts General Hospital for about two days at a time. But that will be changing with the next phase of transitional studies, which must happen before the pivotal, commercial-device studies needed for FDA market approval.
Damiano hopes the pivotal studies could happen in 2015. The FDA hasn't officially finalized guidance for those studies, but the December 2011 draft guidelines about the Artificial Pancreas Project are a step in the right direction.
"These little milestones all add up," he says.
All along, the D-Dad says his goal has been to get to the product FDA-approved by the time his son David goes to college in Fall 2017.
"I have a road map that I think will get us there, but the studies have to bear that out and we're not there yet," he said. "I don't want to put this device on my kid if it doesn't work. A bad artificial pancreas is worse than nothing at all. That could send the whole initiative back, because it will discolor our efforts and the benefits this technology can bring."
As far as keeping tabs on the rest of AP research going on around the country, Damiano says his team learns about new developments at D-conferences and also has a monthly conference call with a consortium of AP parties to hear about progress. With regard to FDA, Damiano says his relationship with the regulatory agency has been nothing but positive, though he points out that he's only dealt with the agency on the research side and not commercialization — which is the more-often-criticized part of the process.
Researchers, Pharma representatives and patient communities all have different definitions for what constitutes "fast" or "slow" when it comes to approving medical devices, Damiano says, and the challenge is making everyone see the process is working. Despite the fact that Damiano wants this product for his son ASAP, he says he couldn't disagree more with the notion that the U.S. is behind other countries as far as medical technology, and he's quick to note they are not being as responsible as the U.S. is.
"Should we be first? I don't think so... we have to do our due diligence," he said. "Our (CGM) sensors aren't good enough and many investigators overseas don't care. They just want a device to put out there. We have to do better."
Damiano says people will modify their behaviors when using a device that does more of the thinking, and that's the danger he sees in this emerging technology. "They'll have confidence in (the AP product) and it's only reasonable that they'll stop thinking about their blood sugar levels all the time and even become less diligent," he said. "That's what worries me — that the technology will come to prime time, and people will wear it like it's ready when it's not."
We appreciate Ed's passion and his work as much as his cautionary words. Thank you, Sir, for devoting your life to this technology!