Notice of Intent to Publish a Funding Opportunity Announcement for Cardiovascular Repository – Type 1 Diabetes (CARE-T1D) Consortium (U01 Clinical Trial Not Allowed).

Key Dates

None

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

National Heart, Lung, and Blood Institute (NHLBI)

The National Institute of Diabetes and Digestive and Kidney Disorders (NIDDK) intends to promote a new initiative by publishing a Notice of Funding Opportunity (NOFO) to solicit applications for research on the cardiovascular complications of type 1 diabetes (T1D) as part of the NIH Cardiovascular Repository for T1D (CaRe-T1D).  Cardiovascular disease (CVD) is the leading cause of death for individuals with T1D and significantly shorten their lives.  CaRe-T1D was initiated with the goal of establishing a biorepository of human CV tissue and a scientific consortium to advance and support discovery and mechanistic research that increase the understanding of CVD in T1D.  The first phase launched the biorepository and now in the second phase investigative teams will be added to form a consortium with the biorepository serving as the Coordinating Center (CC).  The goal of the new initiative is to attract investigative teams with complementary interests and expertise who will leverage these resources through individual and collaborative studies to advance our knowledge of the pathogenesis of CVD in T1D. 

This Notice is being provided to allow potential applicants sufficient time to develop meaningful collaborations and responsive projects. 

The NOFO is expected to be published in Fall 2023 with an expected application due date in Spring 2024.

This NOFO will utilize the U01 activity code. Details of the planned NOFO are provided below.

Background

Cardiovascular disease (CVD) progression in people with T1D differs from that observed in people with type 2 diabetes (T2D).  For example, individuals with T1D are younger at age of disease onset and a disproportionately greater effect is observed in women.  Treatment of standard risk factors, such as hyperglycemia, hypertension, and hyperlipidemia, mitigates some of the higher CVD risk, but residual increased CVD risk remains even with good control of these risk factors.  In addition to atherosclerotic disease, both diastolic and systolic diabetic cardiomyopathies are associated with significant morbidity and mortality.  The pathophysiology of atherosclerosis, cardiomyopathy, endothelial dysfunction, and cardiac autonomic neuropathy in T1D is poorly understood and no therapies are approved to prevent or treat these common, deadly complications of T1D.

CaRe-T1D was initiated through RFA-DK-21-010 and has established a biorepository of human CV tissue. The purpose of the new initiative is to support the next phase of this research program by adding investigative teams to form a consortium with the biorepository serving as the Coordinating Center (CC). CaRe-T1D is currently collecting hearts, kidneys, carotid and peripheral arteries, and blood from organ donors with T1D, T2D and without diabetes.  The tissue is carefully prepared for storage using state-of-the-art procedures and analyzed for tissue quality and pathology using multiple methods. Detailed medical histories are obtained and included in the repository for each tissue.  More information about the tissue, procedures, and analysis can be obtained at the CaRe-T1D website.

Research Goals and Objectives

CaRe-T1D will be the source of well-characterized and preserved human cardiovascular tissue for the consortium. This resource will enable ground-breaking research on human tissue from donors with T1D, T2D, and without diabetes. CaRe-T1D will also serve as the CC and bioinformatics core of the consortium.  The goal of the new initiative is to attract investigative teams with complementary interests and expertise who will make full use of these resources through individual and collaborative studies to advance the knowledge of the pathogenesis of CVD in T1D.

The foundation and driving force of the proposed research should be an understanding of the mechanism of CV disease progression in T1D.  The initiative will support studies that will generate a comprehensive description of molecular, cellular, and structural components of the tissue using state-of-the-art technologies.  However, these studies should not solely focus on data-generation.  Instead, they should mainly be directed at testing hypotheses of disease mechanisms. All CaRe-T1D investigators will be expected to work closely and collaboratively with their CaRe-T1D colleagues and contribute to an environment of cooperation.  The research will include studies that can be completed within the individual U01 investigative teams with the aim of scientific collaboration among the CaRe-T1D investigators to address new opportunities and larger scientific questions.

The research must primarily focus on CVD in T1D using the CaRe-T1D human tissue resources.   CaRe-T1D also has tissue from donors with T2D or without diabetes that can be used for comparisons with T1D.  Research examples include but are not limited to:

• Investigate possible inflammasome activation by T1D within atherosclerotic lesions by cellular and molecular pathway analysis.
• Study altered mitochondrial metabolism and post-translational protein modifications in specific cell types involved in atherosclerosis found in T1D.
• Examine the differences in gene regulation, protein expression and extracellular matrix organization in fibrotic versus calcified carotid plaque.
• Explore the molecular profile that is associated with persistent ventricular remodeling, fibrosis, and mRNA expression that lead to myocardial contractile dysfunction.
• Evaluate mechanisms of the additive effect of hyperglycemia and a dysfunctional immune response in inducing myocardial injury.
• Investigate the pathophysiologic mechanisms for T1D-related small vessel disease and the resulting fibrosis, often leading to heart failure with preserved ejection fraction (HFpEF).
• Explore the mechanisms of cardiac autonomic neuropathy through analysis of microvascular damage of the neuronal capillary networks.
• Study possible mechanisms that link the high-density lipoprotein (HDL) proteome, kidney disease and arterial calcification through analysis of blood and kidney and arterial tissue.
• Utilize CaRe-T1D tissue to develop organ-on-a-chip devices for mechanistic studies and modeling cardiovascular pathophysiology resulting from T1D.

Potential applicants are encouraged to attend a video conference call scheduled for November 27, 2023, at 11 am ET when CaRe-T1D investigators and NIH staff will present an overview of the CaRe-T1D program, resources and website.  Contact Dr. Teresa Jones [email protected] for an invitation to the video conference.

Funding Information

Public/State Controlled Institution of Higher Education
Private Institution of Higher Education
Nonprofit with 501(c)(3) IRS Status (Other than Institution of Higher Education)
Small Business
For-Profit Organization (Other than Small Business)
State Government
Indian/Native American Tribal Government (Federally Recognized)
County governments
Independent school districts
Public housing authorities/Indian housing authorities
Indian/Native American Tribally Designated Organization (Native American tribal organizations (other than Federally recognized tribal governments)
U.S. Territory or Possession
Indian/Native American Tribal Government (Other than Federally Recognized)
Non-domestic (non-U.S.) Entity (Foreign Organization)
Regional Organization
Eligible Agencies of the Federal Government

Applications are not being solicited at this time. 

Inquiries

Please direct all inquiries to:

Teresa L. Z. Jones, M.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-435-2996
Email: [email protected]