NIDDK High Risk Multi-Center Clinical Study Cooperative Agreement (U01 Clinical Trial Required)

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the U.S. Department of Health and Human Services’ National Institutes of Health (NIH), released a funding opportunity titled “High Risk Multi-Center Clinical Study Cooperative Agreement (U01 Clinical Trial Required).” This opportunity supports investigator-initiated therapeutic clinical trials conducted across multiple sites that involve high-risk interventions or operational complexity. The overarching goal is to advance clinical practice and public health through research on diseases under NIDDK’s mission, including diabetes, metabolic and endocrine disorders, digestive diseases, obesity, nutritional disorders, and kidney, urologic, and hematologic conditions. This Notice of Funding Opportunity (NOFO) supports full-scale, hypothesis-driven therapeutic clinical trials designed to test interventions under either pragmatic or controlled conditions. Trials must address clinically significant questions likely to shift practice paradigms. Mechanistic or observational studies are not eligible under this NOFO. All trial planning must be completed before applying—this includes the development of research protocols, recruitment strategies, data collection systems, safety monitoring plans, and IRB submissions. Applicants needing time for such preparation must instead apply to the companion U34 planning award. For those ready to initiate trial activities, this U01 mechanism allows launch-ready studies that can begin recruitment upon award. A high-risk trial in this context includes interventions with unknown safety profiles, substantial side effects, or significant coordination complexity, such as interventional drug/device trials requiring FDA IND or IDE applications. Studies involving complex data collection, operational risks, or research in vulnerable populations also qualify. Operational risk may stem from investigator inexperience, multi-site coordination, or regulatory obligations. Applications must clearly define study designs, address potential biases, and explain how the results will impact care delivery. Eligible applicants include a wide array of U.S.-based organizations: public and private institutions of higher education, nonprofits, for-profit small and large businesses, local and state governments, tribal entities, school districts, and housing authorities. Foreign organizations cannot apply as lead applicants but may participate as collaborators. Each application must present a single clinical trial, and the protocol must be complete at submission. NIDDK prioritizes community and stakeholder engagement, particularly among populations disproportionately affected by relevant diseases. Proposals should describe meaningful partnerships with patients, communities, or advocacy groups and include plans for dissemination of results. Applications may be submitted via Grants.gov, NIH’s ASSIST system, or institutional submission systems. Submissions must conform to both the NIH Application Guide and the program-specific instructions. Requirements include detailed budgets, milestone plans, safety and data monitoring procedures, engagement documentation, and planning activities summaries. Applications without required components, such as the full protocol or milestone plan, will be considered incomplete. This NOFO follows NIH’s standard due dates for new, renewal, and resubmission applications, with deadlines falling on February 5, June 5, and October 5 annually, through January 28, 2026 (expiration date). The anticipated earliest project start dates range from December 2025 to July 2027, depending on the review cycle. While this specific opportunity is now expired, NIH may still consider submissions on a case-by-case basis under its late or continuous submission policy, and a successor opportunity may be anticipated on a recurring annual schedule. Interested parties are encouraged to consult with relevant NIDDK scientific contacts well in advance of submission.