NCCIH Natural Product Mid Phase Clinical Trial (R01 Clinical Trial Required) | PAR 25 271

Opportunity Information: Apply for PAR 25 271

The NCCIH Natural Product Mid Phase Clinical Trial opportunity (PAR 25-271) is an NIH grant program that funds investigator-initiated, mid-phase clinical trials focused on natural products. In this context, natural products include botanicals, dietary supplements, probiotics, and also well-defined nutritional regimens that standardize a specific naturally occurring compound such as omega-3 fatty acids, anthocyanidins, or polyphenols. The central goal is to support studies that are ready for more rigorous clinical testing because they are backed by a strong scientific rationale and convincing early evidence, but that still need key mid-phase answers before moving to a larger, multi-site efficacy trial.

A major emphasis of this NOFO is that proposed trials must be grounded in mechanistic and translational evidence, not just general signals of benefit. Applications are expected to include sufficient preliminary data showing bioavailability when relevant (for example, evidence the compound or its active metabolites can be detected at meaningful levels in the body) and, critically, documentation that the product produces a reproducible and measurable impact on target engagement. Target engagement here means a measurable indicator that the product is acting on the intended biological pathway or mechanism of action, helping justify why the intervention should work and providing a way to interpret clinical outcomes. NCCIH notes that this requirement may be waived only in limited situations, such as when measuring target engagement in the intended patient population is not feasible or practical, or when the mechanism of action is fundamentally well understood.

The clinical trials supported under this program are specifically mid-phase and are meant to generate information that makes a later definitive trial feasible and well-designed. Proposed studies should be built to do one or both of the following: (1) determine the optimal dose or formulation of a natural product to carry forward into a future multi-site efficacy trial, or (2) identify which patient phenotypes are likely to respond versus not respond, so that inclusion and exclusion criteria for a future efficacy trial can be sharpened. In other words, the program is geared toward de-risking the next stage by refining dose, formulation, and patient selection based on biologically informed evidence rather than trial-and-error.

NCCIH also sets clear boundaries on what it will not fund through this NOFO. It is not intended to support single-site or multi-site efficacy or effectiveness trials, meaning the program is not paying for the final, confirmatory test of whether the product works in the broad sense. It also will not support trials testing natural products for the treatment or prevention of cancer. Studies are expected to be hypothesis-driven and milestone-based, aligning directly with NCCIH research priorities and mission, with clear go/no-go decision points and measurable progress markers appropriate for clinical trial management.

On eligibility and administrative details, this is a discretionary NIH grant mechanism using the R01 format with the designation "Clinical Trial Required," meaning applicants must be proposing an actual clinical trial rather than a non-trial clinical study. The activity category is Health (CFDA 93.213). A wide range of U.S.-based applicants can apply, including state and local governments, public and private institutions of higher education, federally recognized tribal governments, tribal organizations (including those other than federally recognized), nonprofits with or without 501(c)(3) status, for-profit organizations other than small businesses, and small businesses, among others. The NOFO also highlights inclusion of institutions such as HBCUs, Hispanic-serving institutions, AANAPISIs, tribal colleges and universities, Alaska Native and Native Hawaiian Serving Institutions, faith-based or community-based organizations, and U.S. territories or possessions. However, foreign organizations are not eligible to apply, and non-U.S. components of U.S. organizations are also not eligible.

Timing-wise, the listed original closing date is 2026-11-13, and the funding opportunity was created on 2024-12-02. The posting does not specify an award ceiling or expected number of awards in the provided source text. Finally, NCCIH encourages prospective applicants to contact the relevant NCCIH scientific or research program contact before submitting, which is a practical signal that program staff input is valued to ensure the proposed trial fits the institute's scope and the mid-phase intent of the NOFO.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "NCCIH Natural Product Mid Phase Clinical Trial (R01 Clinical Trial Required)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.213.
• This funding opportunity was created on 2024-12-02.
• Applicants must submit their applications by 2026-11-13. (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 PAR 25 271

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