NIH funding first artificial pancreas study in pregnant women

A consortium of four leading institutions has begun enrolling women with type 1 diabetes for the first of several clinical trials designed to test the safety and efficacy of a closed-loop insulin delivery system adapted for pregnancy, with the effort funded by a grant from the NIH.

The project includes researchers from the John A. Paulson School of Engineering and Applied Sciences at Harvard University, who will provide algorithm support, as well as a clinical research consortium of specialists from the Icahn School of Medicine at Mount Sinai, the Mayo Clinic and the Sansum Diabetes Research Institute. In a press release announcing the effort, researchers said they hope that the first-in-the-nation studies will lead to a safe and effective at-home clinical trial of an artificial pancreas for pregnant women with diabetes, with an extension phase to the end of pregnancy.

Carol Levy

Endocrine Today spoke with Carol Levy, MD, clinical director of the Mount Sinai Diabetes Center and a principal investigator for the project, about glucose management in pregnant women with diabetes, her own challenges living with type 1 diabetes and the unmet need for artificial pancreas technology in this patient population.

This NIH grant will bring together four institutions to adapt closed-loop insulin delivery technology for pregnant women with type 1 diabetes. How do you all plan to work together?

Levy: Our centers have collaborated for years in the development of closed-loop systems for people with diabetes. For the last 2 years, all four of our research teams have shared a strong interest in expanding the populations studied in closed-loop systems and meeting customized needs for specific groups of people with type 1 diabetes, and one of those key populations is pregnant women. Three of these four sites are clinical sites and will be enrolling patients and studying them. Within each site are physician and research team members with expertise in artificial pancreas systems. We work very closely with Eyal Dassau, PhD, an engineer at Harvard, who is an expert on the algorithm design and customization.

What will make a pregnancy-specific closed-loop insulin delivery system different from the FDA-approved system that is currently available? Why must an automated insulin delivery system be adapted for pregnancy?

Levy: The differences are based on different glucose targets for pregnant women with type 1 diabetes, the algorithm used and the glucose sensor worn by study patients. The only currently FDA-approved system, the Medtronic 670G, is designed to achieve glucose targets for people with type 1 diabetes of 120 mg/dL. For a pregnant woman with type 1 diabetes, the goal for a fasting and premeal blood glucose level is under 90 mg/dL and 1-hour postmeal blood glucose between 130 mg/dL and 140 mg/dL. The 670G is not designed to achieve those glucose targets .

Glucose management for pregnant women with diabetes can be especially challenging. What complicate s diabetes management in pregnancy, and how would an artificial pancreas help to alleviate that burden?

Levy: The challenge for all pregnant women with type 1 diabetes relates to these stringent blood glucose levels required to achieve the best fetal outcomes. Attaining these glucose targets need to be balanced with the risk for hypoglycemia for the mother. The whole purpose of the closed loop is to allow a device to make more accurate dosing decisions in real time in a more efficient fashion than a patient can make. Many pregnant women work very hard to manage their blood sugar, but still struggle with highs and lows. Women who wear glucose sensors are unable to continuously watch their devices, which provide feedback every 5 minutes . They are also not able to adjust insulin delivery based on anticipated future values in the same way that an artificial pancreas can. It is the moment-to-moment insulin dosing decisions these devices can deliver that make these systems work so efficiently. Pregnant women with type 1 diabetes typically test their blood sugars seven to eight times per day and many wear glucose sensors, but still struggle tremendously over their 9-month pregnancy to keep their blood sugar levels in target ranges. These systems have the potential to provide huge benefit, especially overnight, for these women when they are sleeping. There are so many factors that can occur in pregnancy, including nausea, food intolerances and changes in insulin sensitivity that make it a condition that is much more difficult to manage vs. a standard patient with type 1 diabetes.

The first clinical trial in this grant Longitudinal Observation of Insulin Requirements and Sensor Use in Pregnancy ( LOIS-P ) is named for Lois J o vanovic, MD , former d irector and chief scientific officer at the Sansum Diabetes Research Center . LOIS-P is enrolling pregnant women with type 1 diabetes and will follow their glycemic outcomes throughout pregnancy. How did J o vanovic’s research in this field pave the way for a study like this?

Levy: Our team discussed the name for this study and we wanted to honor Lois. Lois Jovanovic spent most of her career at Sansum, where her passion was developing treatments for women with diabetes in pregnancy, as well as the whole concept of artificial pancreas systems. From the beginning, even when I was an endocrine fellow, I would always look to Lois as a mentor and a leader in this area. We all agreed that we would have been missing a key leader in this field by not acknowledging Lois for our project. She recently passed away, and we felt this would be a wonderful way to honor her memory.

If studies go well, how soon can pregnant women expect to have a closed-loop insulin delivery system as an option to help manage their diabetes?

Levy: Clinical trials take time to complete and the FDA needs time to review and approve devices. Our study is for the first system in the United States, and I believe, the first specifically customized closed-loop system adapted for pregnancy. I anticipate that it would take several years before these are available commercially, but in the interim, we are performing studies to learn more about the needed algorithms in conjunction with the benefits of continuous glucose monitoring in this population. The LOIS-P study is helping us to provide guidance for algorithms, helping us to determine more about the benefit of glucose sensors in pregnant women.

I view this work as critical for patients and I have a personal perspective as well. I have had type 1 diabetes for 48 years. I know the path that Lois walked. I managed my diabetes with my health care team through two pregnancies, and I can tell you, every day was a challenge. Caring clinicians are important, and any support that people with type 1 diabetes can have provides a huge difference. Every time I enroll a patient in the LOIS-P study, I feel like we are one step closer to a real answer for many women. – by Regina Schaffer

Disclosure: Levy reports no relevant financial disclosures.

A consortium of four leading institutions has begun enrolling women with type 1 diabetes for the first of several clinical trials designed to test the safety and efficacy of a closed-loop insulin delivery system adapted for pregnancy, with the effort funded by a grant from the NIH.

The project includes researchers from the John A. Paulson School of Engineering and Applied Sciences at Harvard University, who will provide algorithm support, as well as a clinical research consortium of specialists from the Icahn School of Medicine at Mount Sinai, the Mayo Clinic and the Sansum Diabetes Research Institute. In a press release announcing the effort, researchers said they hope that the first-in-the-nation studies will lead to a safe and effective at-home clinical trial of an artificial pancreas for pregnant women with diabetes, with an extension phase to the end of pregnancy.

Carol Levy

Endocrine Today spoke with Carol Levy, MD, clinical director of the Mount Sinai Diabetes Center and a principal investigator for the project, about glucose management in pregnant women with diabetes, her own challenges living with type 1 diabetes and the unmet need for artificial pancreas technology in this patient population.

This NIH grant will bring together four institutions to adapt closed-loop insulin delivery technology for pregnant women with type 1 diabetes. How do you all plan to work together?

Levy: Our centers have collaborated for years in the development of closed-loop systems for people with diabetes. For the last 2 years, all four of our research teams have shared a strong interest in expanding the populations studied in closed-loop systems and meeting customized needs for specific groups of people with type 1 diabetes, and one of those key populations is pregnant women. Three of these four sites are clinical sites and will be enrolling patients and studying them. Within each site are physician and research team members with expertise in artificial pancreas systems. We work very closely with Eyal Dassau, PhD, an engineer at Harvard, who is an expert on the algorithm design and customization.

What will make a pregnancy-specific closed-loop insulin delivery system different from the FDA-approved system that is currently available? Why must an automated insulin delivery system be adapted for pregnancy?

Levy: The differences are based on different glucose targets for pregnant women with type 1 diabetes, the algorithm used and the glucose sensor worn by study patients. The only currently FDA-approved system, the Medtronic 670G, is designed to achieve glucose targets for people with type 1 diabetes of 120 mg/dL. For a pregnant woman with type 1 diabetes, the goal for a fasting and premeal blood glucose level is under 90 mg/dL and 1-hour postmeal blood glucose between 130 mg/dL and 140 mg/dL. The 670G is not designed to achieve those glucose targets .

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Glucose management for pregnant women with diabetes can be especially challenging. What complicate s diabetes management in pregnancy, and how would an artificial pancreas help to alleviate that burden?

Levy: The challenge for all pregnant women with type 1 diabetes relates to these stringent blood glucose levels required to achieve the best fetal outcomes. Attaining these glucose targets need to be balanced with the risk for hypoglycemia for the mother. The whole purpose of the closed loop is to allow a device to make more accurate dosing decisions in real time in a more efficient fashion than a patient can make. Many pregnant women work very hard to manage their blood sugar, but still struggle with highs and lows. Women who wear glucose sensors are unable to continuously watch their devices, which provide feedback every 5 minutes . They are also not able to adjust insulin delivery based on anticipated future values in the same way that an artificial pancreas can. It is the moment-to-moment insulin dosing decisions these devices can deliver that make these systems work so efficiently. Pregnant women with type 1 diabetes typically test their blood sugars seven to eight times per day and many wear glucose sensors, but still struggle tremendously over their 9-month pregnancy to keep their blood sugar levels in target ranges. These systems have the potential to provide huge benefit, especially overnight, for these women when they are sleeping. There are so many factors that can occur in pregnancy, including nausea, food intolerances and changes in insulin sensitivity that make it a condition that is much more difficult to manage vs. a standard patient with type 1 diabetes.

The first clinical trial in this grant Longitudinal Observation of Insulin Requirements and Sensor Use in Pregnancy ( LOIS-P ) is named for Lois J o vanovic, MD , former d irector and chief scientific officer at the Sansum Diabetes Research Center . LOIS-P is enrolling pregnant women with type 1 diabetes and will follow their glycemic outcomes throughout pregnancy. How did J o vanovic’s research in this field pave the way for a study like this?

Levy: Our team discussed the name for this study and we wanted to honor Lois. Lois Jovanovic spent most of her career at Sansum, where her passion was developing treatments for women with diabetes in pregnancy, as well as the whole concept of artificial pancreas systems. From the beginning, even when I was an endocrine fellow, I would always look to Lois as a mentor and a leader in this area. We all agreed that we would have been missing a key leader in this field by not acknowledging Lois for our project. She recently passed away, and we felt this would be a wonderful way to honor her memory.

PAGE BREAK

If studies go well, how soon can pregnant women expect to have a closed-loop insulin delivery system as an option to help manage their diabetes?

Levy: Clinical trials take time to complete and the FDA needs time to review and approve devices. Our study is for the first system in the United States, and I believe, the first specifically customized closed-loop system adapted for pregnancy. I anticipate that it would take several years before these are available commercially, but in the interim, we are performing studies to learn more about the needed algorithms in conjunction with the benefits of continuous glucose monitoring in this population. The LOIS-P study is helping us to provide guidance for algorithms, helping us to determine more about the benefit of glucose sensors in pregnant women.

I view this work as critical for patients and I have a personal perspective as well. I have had type 1 diabetes for 48 years. I know the path that Lois walked. I managed my diabetes with my health care team through two pregnancies, and I can tell you, every day was a challenge. Caring clinicians are important, and any support that people with type 1 diabetes can have provides a huge difference. Every time I enroll a patient in the LOIS-P study, I feel like we are one step closer to a real answer for many women. – by Regina Schaffer

Disclosure: Levy reports no relevant financial disclosures.