NIDDK High Risk Multi-Center Clinical Study Cooperative Agreement (U01 Clinical Trial Required) | PA 25 147

Opportunity Information: Apply for PA 25 147

The NIDDK High Risk Multi-Center Clinical Study Cooperative Agreement (U01 Clinical Trial Required) is a National Institutes of Health funding opportunity (PA 25-147; CFDA 93.847) designed to support investigator-initiated, hypothesis-driven clinical trials that are both high risk and multi-center, meaning the work must involve more than one clinical site. The intent is to back studies that could realistically shift clinical practice and/or have a meaningful public health impact, rather than smaller exploratory projects or single-site trials. The clinical focus must align with the mission of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), so applications should be centered on diseases and conditions within NIDDKs portfolio (for example, diabetes and other endocrine/metabolic conditions, digestive diseases, nutrition-related disorders, and kidney/urologic/hematologic diseases, as applicable to NIDDK priorities).

This award uses the cooperative agreement mechanism (U01), which typically means the funded project is carried out with substantial scientific or programmatic involvement from NIH staff compared to a standard research project grant. In practice, applicants should expect an active partnership model where NIDDK program staff may provide input on trial conduct, milestones, and oversight expectations consistent with NIH cooperative agreement norms. The NOFO is explicitly for clinical trials, and the title indicates that a clinical trial is required, so the proposed research needs to meet the NIH definition of a clinical trial and include the usual components of a rigorously designed trial (clear primary hypothesis, outcomes, statistical plan, recruitment and retention strategy, data and safety oversight approach, and multi-site coordination).

A key feature of this opportunity is that it does not allow planning activities as part of the U01 application. Applicants are expected to have completed the major planning work before submitting, such as finalizing the protocol, establishing site commitments, developing operational plans for recruitment and retention, ensuring data management and monitoring plans are ready, and lining up trial governance and oversight structures. If a team is not yet ready for full implementation and needs time and support to finalize these elements, NIDDK points applicants to an implementation planning cooperative agreement (U34; referenced as TEMP9971) as the appropriate first step. In other words, this U01 is positioned as an implementation-ready mechanism for trials that are already prepared to launch across multiple centers rather than a mechanism that funds the ramp-up and design phase.

NIDDK also strongly encourages consultation with NIDDK scientific/research staff before submitting either a U34 or a U01. That consultation is important because it helps applicants confirm fit with NIDDKs mission and current priorities, clarify expectations for a high-risk multi-center trial under a cooperative agreement, and avoid preventable misalignment issues (for example, proposing work that is not considered implementation-ready, or that does not rise to the level of impact expected for this high-risk clinical trial program).

In terms of who can apply, eligibility is broad and includes many domestic organization types such as state, county, city, and special district governments; independent school districts; public and state-controlled and private institutions of higher education; federally recognized Native American tribal governments; public housing authorities/Indian housing authorities; Native American tribal organizations that are not federally recognized tribal governments; nonprofits with and without 501(c)(3) status (other than institutions of higher education); for-profit organizations other than small businesses; and small businesses. The NOFO also calls out additional categories of eligible applicants, including Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISI), Hispanic-serving Institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), faith-based or community-based organizations, eligible federal agencies, regional organizations, Indian/Native American tribal governments other than federally recognized entities, and U.S. territories or possessions. At the same time, the notice states that non-domestic (non-U.S.) entities are not eligible to apply, and non-domestic components of U.S. organizations are not eligible to apply. However, foreign components, as defined in the NIH Grants Policy Statement, are allowed, which means a U.S. applicant organization may be able to include certain foreign elements consistent with NIH policy even though a foreign organization cannot be the applicant.

Operationally, the opportunity is categorized as discretionary funding using a cooperative agreement instrument, and the activity category is listed under food and nutrition and health. The posted original closing date is 2026-11-05, and the opportunity was created on 2025-01-03. The award ceiling and expected number of awards are not specified in the provided summary, so applicants would typically need to consult the full NOFO text and/or speak with NIDDK staff to understand budget expectations, potential caps, and the likely scale of awards for trials of this type.

Overall, this NOFO is best suited for teams that already have a well-developed, multi-center clinical trial ready to implement, are prepared to work closely with NIDDK under a cooperative agreement structure, and can make a strong case that the trial is hypothesis-driven, high-impact, and relevant to NIDDK-supported disease areas.

• The National Institutes of Health in the food and nutrition, health sector is offering a public funding opportunity titled "NIDDK High Risk Multi-Center Clinical Study Cooperative Agreement (U01 Clinical Trial Required)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.847.
• This funding opportunity was created on 2025-01-03.
• Applicants must submit their applications by 2026-11-05. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

Apply for PA 25 147

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