NIDDK High Risk Multi-Center Clinical Study Cooperative Agreement (U01 Clinical Trial Not Allowed)

The NIDDK High Risk Multi-Center Clinical Study Cooperative Agreement (U01 Clinical Trial Not Allowed) is a funding opportunity administered by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), a component of the U.S. Department of Health and Human Services through the National Institutes of Health (NIH). This initiative supports investigator-initiated, high-risk, multi-center observational studies focused on diseases within NIDDK’s mission, such as diabetes, endocrine disorders, obesity, digestive diseases, and kidney-related conditions. This funding mechanism is specifically structured for projects that do not propose clinical trials but still present significant clinical and operational risks, thus warranting close NIH involvement. The purpose of this opportunity is to facilitate rigorous scientific studies with the potential to significantly advance understanding, prevention, diagnosis, or treatment of NIDDK-relevant diseases. It supports high-risk studies—those involving invasive measures, complex interventions, vulnerable populations, or multi-site coordination challenges. Studies must be hypothesis-driven and demonstrate a high likelihood of substantial clinical impact. Examples include investigations into disease incidence, natural history, risk factors, or diagnostic performance. Applications must focus on a single clinical study and should be informed by meaningful engagement with patients, communities, healthcare providers, or other stakeholders. Eligible applicants include a wide array of public and private institutions, such as higher education institutions, nonprofits, small businesses, and state and local governments. However, foreign organizations and components of U.S. organizations located outside the country are not eligible to apply. Foreign components may be included to contribute scientific input. Cost sharing is not required, and there are no specific award ceilings or floors stated, as budgets must reflect the actual needs of each project. Applications must follow detailed submission requirements including a Clinical Protocol Synopsis, Statistical Analysis Plan, Milestone Plan, and documentation of all completed planning activities. All planning work must be concluded before submission; planning phases are not allowed under this U01 mechanism. Applicants needing additional planning are encouraged to first apply for the U34 planning grant (PAR-25-090). Only one study per application is allowed, and all projects must comply with NIH’s data management, sharing, and human subjects protection policies. Applications for this NOFO follow NIH’s standard due dates: February 5, June 5, and October 5 annually, with renewals or resubmissions due a month later. The final deadline for this NOFO was January 28, 2026, at which point it expired as per NIH Notice NOT-DK-26-104. Given its recurring structure, applicants are encouraged to anticipate the next cycle, which would likely reopen in early 2027, and check the NIH Guide accordingly. For inquiries, designated scientific contacts for each relevant division are listed, as well as a grants management contact for administrative questions.