NCCIH Natural Product Early Phase Clinical Trial Award (R33 Clinical Trial Required) | PAR 25 270

Opportunity Information: Apply for PAR 25 270

The NCCIH Natural Product Early Phase Clinical Trial Award (R33 Clinical Trial Required), Funding Opportunity Number PAR-25-270, is a National Institutes of Health grant program designed to move promising natural product research into early-stage testing in humans. The focus is on investigator-initiated clinical trials of natural products such as botanicals, dietary supplements, and probiotics, as well as certain nutritional regimens that standardize a specific naturally occurring compound (for example omega-3 fatty acids, anthocyanidins, or polyphenols) and are backed by compelling preliminary evidence. The core expectation is that applicants bring a strong scientific premise suggesting the product engages a biologically meaningful target and is ready for rigorous early clinical evaluation.

This opportunity is specifically aimed at early phase, hypothesis-driven, milestone-based clinical trials that generate results with clear decision value. NCCIH is looking for studies where the findings, whether positive or negative, will still be highly informative and will directly support go/no-go decisions about whether a natural product should advance to further development or additional clinical testing. Rather than asking applicants to run broad clinical outcome trials, the NOFO emphasizes mechanistic clarity and scientific utility: it prioritizes trials that can replicate and measure the natural product's impact on target engagement in humans, and then evaluate whether the degree of target engagement is associated with functional or clinical outcomes in a relevant patient population.

The award provides up to 3 years of support to conduct this kind of early translational clinical work. A major theme is optimizing how the natural product is delivered and used so that target engagement is maximized and reliably measured. Applications are encouraged to include designs that compare different doses or formulations to identify the most effective way to achieve the intended biological effect. The NOFO also allows strategies such as combining the natural product with another intervention that is already known to engage the same target, or testing the natural product in a population that may be more responsive, as long as the overall study remains anchored in target engagement and produces interpretable evidence that informs next-step development decisions.

Importantly, this program is not meant to fund efficacy or effectiveness trials. In other words, it is not intended for large-scale studies primarily designed to prove clinical benefit in the way a definitive Phase 3-style trial might. Instead, it supports early phase clinical testing that bridges emerging basic science to human studies, helping determine whether the mechanistic and translational evidence is strong enough to justify larger and more expensive clinical research later.

From an administrative standpoint, the opportunity is a discretionary NIH grant in the health funding activity category (CFDA 93.213). The listed award ceiling is $1,050,000, and the original closing date is 2026-11-13. A wide range of domestic applicant organizations may be eligible, including state, county, and local governments; special district governments; independent school districts; public and private institutions of higher education; federally recognized Native American tribal governments; certain tribal organizations; public housing authorities/Indian housing authorities; nonprofits with and without 501(c)(3) status; for-profit organizations (other than small businesses); and small businesses.

At the same time, the NOFO includes notable eligibility limits. Non-domestic (non-U.S.) entities are not eligible to apply, and non-domestic components of U.S. organizations are also not eligible. The NOFO also specifies that "Other Eligible Applicants" will not include several categories of institutions and organizations, including Alaska Native and Native Hawaiian Serving Institutions, AANAPISIs, Hispanic-serving institutions, HBCUs, TCCUs, faith-based or community-based organizations, regional organizations, U.S. territories or possessions, and certain federal government agencies, among others as listed in the notice. Overall, the program is best understood as a targeted translational mechanism from NCCIH to accelerate careful, early human testing of natural products with strong mechanistic rationale, with an emphasis on target engagement, optimized delivery, and milestone-driven progress rather than broad claims of clinical effectiveness.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "NCCIH Natural Product Early Phase Clinical Trial Award (R33 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.)
• Each selected applicant is eligible to receive up to $1,050,000.00 in funding.
• 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 25 270

[Watch] Creating a grant proposal using the step-by-step wizard inside the applicant portal: