Description of Project
Heart and kidney (cardio-renal) complications are the leading source of morbidities in persons with type 1 diabetes (T1D). However, progression of the condition in everyone is unique based on their genetic, environmental, social and behavioral contexts. The Michigan JDRF Center of Excellence (UMCoE) has established approaches and tools to detect the various ways that T1D affects kidney and heart function. UMCoE studies have identified specific subgroups within T1D, where people have similar mechanisms of organ injury; categorized the ways in which heart and kidney tissue are damaged; and identified specific signatures of blood and urine molecules (biomarkers) linked with each of these damage categories.
In the next phase of the Center of Excellence we propose to establish a T1D Precision Medicine Platform. This pilot study will leverage findings from UMCoE and apply it to match an individual’s T1D organ damage category to available therapies so that the right patient receives the right treatment at the right time. We have already established a similar precision medicine approach for people with kidney filter failure, and will now bring this expertise to people with T1D, (see introduction at NEPTUNE Match.
In a close partnership between the Diabetes Centers of the University of Michigan (UM) and Oregon Health & Science University (OHSU) we will match in the UM-OHSU Cardio-Renal Center of Excellence (UM-OHSU CoE) the mode of action of treatments for heart and kidney diseases with our knowledge about T1D organ damage. We will then use molecular biomarkers to identify and group each participant with T1D to the appropriate damage category, and thereby assign them to the optimal treatment targeting their specific damage type. Therefore, our strategy will implement a biomarker stratified mechanistic study design, in which participants will be grouped based on their disease pathway activation signatures and then matched to the targeted therapies being evaluated in the UM-OHSU T1D precision medicine platform.
To expedite discovery, we will follow all participants closely during the trial, and measure the biomarkers after 6 weeks and 26 weeks (6 months). This will enable us to determine whether each participant is responding to the targeted treatment by comparing various measures before and after treatment. The changes in biomarkers used to assign participants to treatments will also serve as indicators of their future kidney and heart function (prognostic biomarkers).
We will start with a three-drug trial in the pilot phase of the UM-OHSU CoE, bringing therapies for other conditions to our T1D precision medicine platform. This will allow us to rapidly assess their ability to reverse T1D cardio-renal complications, thereby accelerating the availability of cardio-renal treatments for patients with T1D. The platform is highly adaptable, allowing us to incorporate new treatments as they become available, to continuously and rapidly advance delivery of individualized therapies to people with T1D.
Our approach will also enable efficient and robust collection of diverse data sets from clinical information and biosamples provided by study participants in the trial platform. These data will be integrated and shared through the tranSMART database that was developed during the UMCoE phase. We will be eager to broadly share this data with the T1D research community, expanding it to include environmental exposures, social determinants of health, and care delivery trajectories.