Objective
The advanced postdoctoral fellowship award will provide Dr. Akcan with critical protected time to pursue formal coursework, didactic training, and develop an independent research program. Her research experience has provided a solid foundation in the scientific method, data collection, presentation, and publication. The primary objective of the proposed trial is to assess and compare the clinical efficacy and safety of two Loop AID algorithm interventions for pregnant women with T1D. Specifically, the study aims to determine how well these algorithms maintain glucose levels within the target range suggested for pregnancy and their impact on the frequency and severity of low and high blood sugar episodes. The goal is to identify the efficacy and safety of these interventions for managing T1D during pregnancy, ultimately improving health outcomes for both mothers and their babies.
This study will take place over two years at four U.S. sites, including Stanford University. Dr. Akcan will lead the project at the Stanford site.The trial aims to enroll 25 pregnant women with T1D. Participants will be between 8 and 15 weeks pregnant at the start of the study. They will be carefully assessed for eligibility and trained in using the AID system and devices. Participants will be randomly assigned to one of two intervention groups as described in detail above. The study begins with a 40-60 hour supervised phase, followed by 8 weeks of using the AID system at home. After this, participants will switch to the other intervention for another 8 weeks. Once both interventions are completed, participants can choose which plan to continue using for the rest of their pregnancy until delivery. The use of AID technology will stop upon hospital admission or if deemed necessary by the investigator for the participant's safety. During labor and delivery, diabetes management will follow the hospital's standard procedures.Participants will also have the option to use the AID technology until their final study visit, which will occur 6-8 weeks after giving birth. Throughout the study, detailed data will be collected on blood sugar levels, episodes of low and high blood sugar, their severity, and pregnancy outcomes for both mothers and babies.
Upon completing the advanced postdoctoral fellowship, Dr. Akcan will have acquired the knowledge, experience, and data to launch an independent clinical investigator career and compete successfully for future funding. Her long-term research objective is to become a leader in diabetes technology research and improve the lives of people with T1D, prioritizing both maternal and fetal health in pregnant women with T1D.
Background Rationale
T1D poses significant risks during pregnancy, potentially affecting the health of both the mother and her baby. High blood sugar levels around conception can increase the risk of birth defects, stillbirth, and preterm birth. Additionally, women with diabetes, including T1D, face a higher likelihood of requiring a cesarean delivery and having babies who are born too large, which can lead to obesity or type 2 diabetes later in life. Effective management of blood glucose levels is crucial to minimizing these risks.
Traditional insulin delivery methods like insulin injections require frequent adjustments and monitoring, which can be challenging during pregnancy due to rapid changes in insulin needs. Using AID systems during pregnancy can help women with T1D optimize blood sugar control and improve their quality of life. Studies have shown that pregnancy-specific AID systems can enhance glycemic control, improve quality of life, and potentially reduce healthcare costs. However, there is a need to develop algorithms that are safe and approved for pregnancy. Currently, only one AID system, the CamAPS Fx, has been licensed for use during pregnancy, but it is only approved in Europe, the U.K., and Australia. While CamAPS Fx received FDA approval in May 2024, it lacks a pump partner for use in the U.S. Therefore, no AID systems are currently approved for use during pregnancy in the U.S.
AID systems can significantly improve glucose control in pregnant women, but more studies are needed to assess their efficacy and safety and to provide guidance for women with T1D and their healthcare providers. It is essential to refine these algorithms to better align with the unique insulin needs during pregnancy, as any improvement in glucose control can lead to better pregnancy outcomes. The Loop AID algorithm has shown promise in improving glucose control in non-pregnant individuals. This study aims to adapt and evaluate the Loop AID algorithm for pregnancy-specific glucose targets and needs, assessing its efficacy and safety.
Description of Project
Dr. Tugce Akcan is an Endocrinology Fellow in the Division of Adult Endocrinology at Stanford University. She is applying for the Breakthrough T1D Advanced Postdoctoral Fellowship Award to conduct a clinical trial aimed at providing structured clinical research training with formal mentorship. This will enable Dr. Akcan to become an independent clinical researcher specializing in automated insulin delivery (AID).
AID systems combine an insulin pump and continuous glucose monitor (CGM) to help people with Type 1 Diabetes (T1D) manage their blood sugar levels. In addition to the CGM and insulin pump, AID systems consist of a smart algorithm that links the two devices together, allowing them to "talk" to each other. Dr. Akcan's study will evaluate the clinical efficacy and safety of an AID algorithm called "Loop" for pregnant women with T1D.
Managing T1D during pregnancy is particularly challenging due to unique physiological changes and strict glucose control requirements essential for both maternal and fetal health. Historically, women with T1D were advised against having children, but fortunately, the medical field has progressed significantly since then. One revolutionary advancement in managing T1D more effectively is the use of AID systems. In children, adolescents, and adults, AID systems have been shown to improve blood sugar control and enhance quality of life.
Despite these advancements, managing T1D during pregnancy remains challenging due to altered insulin needs and stringent glucose targets required to avoid complications. Currently, only one FDA-approved AID system is available for use during pregnancy, and no other systems are approved or customized to meet the specific glucose targets and needs of pregnant women.
Dr. Akcan's study aims to evaluate the clinical efficacy and safety of the Loop AID algorithm for pregnant women with T1D. The Loop AID algorithm has been modified to accommodate pregnancy-specific lower glucose targets and address physiological changes during pregnancy. This trial will compare two interventions using the Loop algorithm. The first intervention will be clinician-driven with basic algorithm features, while the second will include additional personalized features as suggested by an investigator-driven application. Both interventions will use the Loop AID algorithm with lower glucose targets recommended for pregnant women with T1D. The study will assess their efficacy in glucose control and safety by monitoring instances of low and high blood sugar, as well as any adverse device effects.
In addition to her research, Dr. Akcan will pursue coursework in epidemiology, statistics, study design, human protection, and ethics. This structured training will help her develop the necessary skills to become an expert in diabetes technology. Dr. Akcan's long-term research objective is to advance diabetes care through innovative technology, improving outcomes for people with diabetes, including pregnant women with T1D.
Anticipated Outcome
We anticipate that both interventions of the Loop AID algorithm will improve glucose control during pregnancy compared to the traditional self-managed insulin injection approach. Specifically, we expect to see a higher percentage of time that blood glucose levels remain within the target range advised for pregnancy. Additionally, we aim to identify which intervention of the algorithm offers superior performance in maintaining these levels. We also expect to demonstrate that the Loop AID algorithm is safe for use in pregnant women with T1D by monitoring for any adverse events, such as episodes of low and high blood sugar, and device-related issues.
Relevance to T1D
The proposed study is highly relevant to the field of T1D as it addresses a critical need for improved management of T1D during pregnancy. Pregnant women with T1D face increased risks for themselves and their babies, including birth defects, stillbirth, preterm birth, and delivery complications. Effective blood glucose management during this period is vital for reducing these risks and ensuring healthy outcomes for both mother and child.
Traditional methods of insulin delivery require constant monitoring and adjustment, which can be particularly challenging due to the rapid changes in insulin needs during pregnancy. AID systems have revolutionized diabetes management by integrating insulin pumps with CGMs and smart algorithms that automatically adjust insulin delivery. However, current AID systems in the U.S. are not approved for use during pregnancy, leaving a significant gap in care for pregnant women with T1D. This study aims to fill that gap by adapting and evaluating the Loop AID algorithm for pregnancy-specific glucose targets and needs.
By focusing on the unique physiological changes and strict glucose control requirements during pregnancy, this research has the potential to provide a safer, more effective method for managing T1D in pregnant women. The findings could lead to better health outcomes, reduced healthcare costs, and improved quality of life for women with T1D and their babies. Additionally, this study will contribute valuable data to the ongoing development of diabetes technology, supporting the broader goal of enhancing diabetes care through innovation.