In the State of the Cure 2014 report, the Bionic Pancreas was identified as one of the eight Practical Cure solutions currently in human clinical trials. The Bionic Pancreas, an initiative lead by a collaborative group from Boston University and Massachusetts General Hospital. Dr. Edward Damiano, Principal Investigator, shares details about the progress of this project.
The Bionic Pancreas is a bi-hormonal closed-loop pump and continuous glucose monitoring device. The system delivers insulin and glucagon, and measures and adapts to each individual in real time. The following interview with Dr. Damiano shares details about the project.
Cara Murphy: Why did your team get involved in t1d research?
Dr. Edward Damiano: I began work in T1D research soon after my son, David, was diagnosed with T1D as an infant over 14 years ago. My co-developer of the bionic pancreas, Firas El-Khatib, was a graduate student of mine at the time David was diagnosed and took on the problem of developing mathematical control algorithms for making automated therapeutic dosing decisions for administering insulin and glucagon for a bihormonal bionic pancreas system. This theoretical work, along with our first preclinical experiments testing the system in diabetic pigs, became the substance of his PhD thesis, which he completed nine years ago.
CM: How long have you been at it and what kept everyone going?
ED: Dr. El-Khatib and I have continued to work steadily on the project since 2001. In the fall of 2004, after I moved my lab to Boston University (BU), we began pre-clinical experiments in diabetic pigs. In the spring of 2006 we met our clinical collaborator, Steven Russell, at the Massachusetts General Hospital (MGH). In the summer of 2008 we began our first human inpatient trial testing the laptop version of our bionic pancreas in the clinical research center at MGH. We continued inpatient studies for over four years at MGH until the end of 2012. In early 2013 we began our first human outpatient trial testing the iPhone version of our bionic pancreas. Since then, we have completed three outpatient trials (one in adults, one in adolescents, and one in pre-adolescents) and are halfway through our first multi-center trial in adults with T1D wearing the bionic pancreas for 11 days at home and at work. I have been laser focused on developing, testing, and delivering a bionic pancreas to people with T1D by the time David heads off to college in the fall of 2017. This has been my unwavering goal since the beginning of the project and has provided me with all of the motivation and incentive I have drawn upon over the years.
CM: Please describe to us non-scientists the Bionic Pancreas approach? What makes it unique?
ED: Our bionic pancreas is a portable medical device, a little larger than a smartphone, that takes over diabetes management decisions for people with T1D. In deference to millions of years of evolution, our bionic pancreas mimics biology and uses both insulin (to lower blood glucose) and glucagon (to raise blood glucose) to automatically regulate glycemia in T1D. The system consists of a continuous glucose sensor, an infusion system to pump insulin and glucagon through the skin, and mathematical algorithms transcribed in software that make therapeutic decisions every five minutes to determine each dose of insulin and glucagon. Over the years it has evolved from a crude and clumsy system of interconnected components of pumps and sensors cobbled together around a laptop computer, to a system that runs in an app on an iPhone that can be carried in your pocket, and finally to its ultimate embodiment as a dual-chamber infusion pump, a sensor, and all of our mathematical algorithms all housed within a single compact integrated device.
Our bionic pancreas is unique in its ability to provide a comprehensive and fully automated diabetes management solution for people with T1D. All that is required for the device to come online is that the patient enter their body mass. No information about the patient’s daily insulin regimen is required to start the system. This is particularly important for patients who are newly diagnosed with T1D as such information is generally not known; initial therapy is arrived at heuristically and often requires significant changes throughout the honeymoon period, confounding patients’ ability to gain confidence as they transition to life with T1D. Our bionic pancreas is capable of continuous and robust adaptation to the each patient’s ever-changing individual insulin requirements. As such, it spares the patient from ever having to count carbohydrates or determine carb-to-insulin ratios, basal rates, insulin sensitivity, or correction factors. Newly diagnosed people with T1D would never need to learn current standard-of-care diabetes management practices, and those who have lived with T1D will never have to think about them again. It is truly a turnkey solution for people with T1D.
CM: If successful, how will this change the day-to-day lives of people living with t1d?
ED: The bionic pancreas is not a cure – it is a bridge to a cure. It is a transformative technology for T1D management, the likes of which have not been seen since the discovery and purification of insulin nearly a century ago. What makes it different from all other diabetes medical devices that have come before it is that it offers a holistic, fully automated systems approach to glycemic control, rather than just providing a component technology that addresses only one part of the glycemic control challenge (e.g. insulin infusion, glucose sensing, therapeutic dosing decisions, etc.). The bionic pancreas simultaneously solves the four greatest concerns of T1D management: (1) it reduces mean glycemia in everyone to levels that would exceed the American Diabetes Association’s goal for therapy, and would likely eradicate all long-term microvascular and neurological complications, (2) it profoundly curtails mild hypoglycemia in everyone, and would likely eliminate any risk of severe hypoglycemia, (3) it automates glycemic management, thus unburdening everyone touched by T1D of the relentless need to comply with therapy, as the bionic pancreas itself is the first technology to be entirely compliant with the patient’s needs rather than the other way around, and (4) it unburdens everyone touched by T1D of the emotional hardship that is, for now, part of everyday life, and of the constant fear of hypoglycemia, and of the worry and dread of long-term complications. A device that solves any one of these concerns would be groundbreaking; a device that simultaneously solves all four is without precedent and game changing.
CM: What are the biggest hurdles you foresee in successfully delivering the project?
ED: There are many hurdles to overcome on the road that lies ahead, but none of them are insurmountable. These include fundraising efforts (NIH, private foundations, philanthropy), technical challenges (device, drug, and clinical), fostering constructive relationships between industry and academia, coordinating numerous overlapping timelines, satisfying regulatory requirements, navigating the reimbursement landscape, raising awareness and influencing priorities to favor the bionic pancreas initiative in every facet of this project (industry, academia, FDA, CMS, NIH, private foundations, private payers, health care providers, patients, caregivers, and the media).
CM: At what stage of human trials are you? Are you still recruiting? If so, how can one be considered for participation?
ED: We are currently testing the iPhone implementation of our system in real-world outpatient trials at multiple centers across the country. These experiments will continue throughout 2015. We will continue to recruit subjects for these studies throughout 2015 and for the final pivotal trail in 2016. Those interested in participating should contact either Raj Setty (email@example.com) in my group at BU, or Kendra Magyar (KLMAGYAR@mgh.harvard.edu) on our clinical team at MGH. We maintain a list of names and contact information for prospective study participants so that we can reach out to those interested as new clinical trial opportunities arise.
CM: What is the path from here to ‘bedside’?
ED: In parallel with these clinical studies, we are working with our industrial collaborators to build the final version of our bionic pancreas, which will be a fully integrated dual-chamber device that integrates a continuous glucose monitor and all of our mathematical algorithms into a single handheld device. This device will operate completely independently of a smartphone. We plan to have our dual-chamber bionic pancreas and dual-cannula infusion set completed in about 12 months (late 2015). Our goal is to conduct the final pivotal trial testing this device in 2016 and submit the Pre-Market Approval application to the FDA in early 2017. Depending on the length of the regulatory review process, we are hoping we can obtain FDA approval and make the technology broadly available in the US in the second half of 2017, in time for David to go to college.