NCCIH Natural Product Early Phase Clinical Trial Award (R33 Clinical Trial Required) | PAR 24 116

Opportunity Information: Apply for PAR 24 116

The NCCIH Natural Product Early Phase Clinical Trial Award (R33 Clinical Trial Required) (PAR-24-116) is a National Institutes of Health funding opportunity that supports investigator-initiated early phase clinical trials focused on natural products. The program is meant to move promising natural product science from strong preclinical or preliminary human evidence into carefully designed early clinical testing that can answer practical go/no-go questions about whether the product is worth further development. NCCIH is specifically looking for projects that align with its mission and research priorities and that are built around a clear, hypothesis-driven scientific rationale rather than exploratory or loosely defined clinical testing.

The natural products of interest include botanicals, dietary supplements, and probiotics, as well as certain nutrition-based regimens when they standardize the amount of a specific naturally occurring compound and have compelling preliminary evidence. Examples named in the announcement include standardized regimens involving compounds such as omega-3 fatty acids, anthocyanidins, or polyphenols. A key expectation is that the proposed trial will produce results with high scientific utility regardless of whether the findings are positive or negative. In other words, the trial design should be strong enough that the outcome clearly informs next steps, such as whether to proceed to additional clinical research, refine the intervention, or discontinue development.

A central feature of this NOFO is its emphasis on target engagement in humans. Supported studies are expected to replicate and measure the impact of the natural product on a defined biological target when used by people, and then evaluate whether the degree of target engagement is associated with functional or clinical outcomes in a patient population. The intent is to strengthen the causal chain between the intervention and a biologically plausible mechanism, while also gathering early clinical signals that help interpret whether the mechanism matters for patients.

The NOFO also encourages applicants to optimize how the natural product achieves target engagement. This can include testing different doses, comparing formulations, or otherwise improving delivery and exposure to increase the likelihood of observing a measurable biological effect. Additional acceptable strategies include pairing the natural product with another treatment approach already known to engage the same target, or selecting a target population that is more likely to respond based on biology or prior evidence. Across these options, trials are expected to be milestone-driven, meaning applicants should define clear, measurable progress points that determine whether the project is on track and whether continued investment is justified.

This award provides up to 3 years of support under the NIH R33 mechanism, which is designed to accelerate translation into early-stage clinical testing. Importantly, this program is not intended to fund full efficacy or effectiveness trials. The focus is earlier: demonstrating and characterizing target engagement, linking it to outcomes, and generating decision-quality evidence about whether larger, later-phase trials are warranted.

Key administrative details include an award ceiling of $1,050,000 and an original closing date listed as 2026-11-13. The assistance listing (CFDA) number is 93.213, the opportunity category is discretionary, and the activity area is health. Eligible applicants are broad across U.S.-based organizations and include state, county, and local governments; special district governments; independent school districts; public and private institutions of higher education; federally recognized Native American tribal governments; tribal organizations (other than federally recognized tribal governments); public housing authorities/Indian housing authorities; nonprofits with or without 501(c)(3) status (other than institutions of higher education); for-profit organizations (other than small businesses); small businesses; and other eligible entities as described in the announcement.

At the same time, the NOFO includes several specific eligibility limitations. Non-domestic (non-U.S.) entities are not eligible to apply, and non-domestic components of U.S. organizations are not eligible to apply. Foreign components, as NIH defines them in the NIH Grants Policy Statement, are allowed, which typically means discrete project elements may be performed outside the U.S. under NIH rules even though the applicant organization must be eligible and domestic. The notice also states that "Other Eligible Applicants" will not include several categories such as Alaska Native and Native Hawaiian Serving Institutions, AANAPISISs, faith-based or community-based organizations, Hispanic-serving institutions, HBCUs, tribally controlled colleges and universities, regional organizations, U.S. territories or possessions, eligible agencies of the federal government, and certain non-federally recognized tribal governments. Applicants should read those exclusions carefully and confirm how they apply to their institution type.

Overall, PAR-24-116 is best viewed as a mechanism for rigorously testing whether a well-justified natural product intervention truly engages a specified biological target in humans, whether that engagement relates to meaningful clinical or functional measures, and whether optimizing dose/formulation or selecting the right population can strengthen the signal. The program is designed to produce decision-ready evidence that guides whether the natural product should advance to later-stage clinical research, rather than to deliver definitive proof 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 2024-02-01.
• 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.

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