NCCIH Natural Product Early Phase Clinical Trial Award (R33 Clinical Trial Required) | PAR 18 828

Opportunity Information: Apply for PAR 18 828

The NCCIH Natural Product Early Phase Clinical Trial Award (R33 Clinical Trial Required), funding opportunity number PAR-18-828, is a National Institutes of Health grant program designed to move promising natural product research into early-stage clinical testing. It focuses specifically on investigator-initiated clinical trials of natural products such as botanicals, dietary supplements, and probiotics, but only when there is a strong scientific premise suggesting the product is likely to affect a meaningful biological target in humans. The intent is not to fund broad exploratory studies or late-stage clinical testing, but to support carefully designed early phase trials that can decisively inform whether a natural product is worth further development.

A central feature of this opportunity is its emphasis on biological signatures, meaning measurable biological indicators or pathways that the natural product is expected to influence based on prior evidence. Funded studies are expected to replicate and confirm the natural product's impact on these biological signature(s) in humans and then evaluate whether the extent of that biological impact is associated with functional or clinical outcomes in a patient population. In practice, this means the trial should not just measure whether participants feel better, but should connect outcomes to a mechanistic readout that helps explain how and why the intervention may be working (or not working). Importantly, NCCIH expects that results will be highly informative regardless of whether they are positive or negative, so the study design needs to be rigorous enough that a null result still provides a clear answer and supports a rational go/no-go decision about next steps.

The FOA supports up to three years of project support and encourages milestone-driven, hypothesis-based trials aligned with NCCIH's mission and research priorities. Applicants may also propose strategies to optimize how a natural product affects the targeted biological signature. The announcement highlights three main optimization approaches: adjusting delivery through dose or formulation, combining the natural product with another treatment known to influence the same biological signature, or selecting a target population that is more likely to respond (for example, based on baseline biology, disease subtype, or other response predictors). This makes the program particularly suited for translational projects that already have a plausible mechanism and preliminary evidence, and now need early human data to refine dosing, formulation, combination approaches, or population selection before larger trials are considered.

At the same time, the program draws clear boundaries around what it will not fund. It is not intended for full efficacy or effectiveness trials, meaning trials designed primarily to determine whether a natural product definitively treats a condition in real-world or large-scale settings. It also will not support clinical trials testing natural products for the treatment or prevention of cancer. The overall role of this R33 mechanism is to accelerate translation from emerging basic and preclinical findings into early clinical testing that can clarify promise, mechanism, and next-step feasibility, rather than to deliver final clinical practice answers.

In terms of eligibility, the opportunity is broadly open across many U.S.-based organization types, including state, county, and local governments; public and private institutions of higher education; independent school districts; special district governments; federally recognized Native American tribal governments and other tribal organizations; public housing authorities/Indian housing authorities; nonprofits with or without 501(c)(3) status; for-profit organizations (other than small businesses) as well as small businesses; and other eligible entities. It also explicitly notes inclusion of certain institution types and community-linked organizations, such as Historically Black Colleges and Universities (HBCUs), Hispanic-serving Institutions, Tribally Controlled Colleges and Universities (TCCUs), Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISIs), faith-based or community-based organizations, regional organizations, and eligible federal agencies, as well as U.S. territories or possessions. However, foreign involvement is tightly restricted: non-U.S. (foreign) institutions are not eligible to apply, non-domestic components of U.S. organizations are not eligible, and foreign components as defined by NIH policy are not allowed.

Administratively, this is a discretionary grant in the health funding activity category (CFDA 93.213) administered by NIH through NCCIH. The source information lists an award ceiling of $1,050,000 and shows an original closing date of November 4, 2019, indicating the specific posting referenced is from the 2018-2019 cycle (created June 13, 2018). Even so, the program description captures the core aims and requirements: early phase, mechanism-informed clinical trials of natural products, built to produce high-utility evidence that helps determine whether additional clinical research is justified.

• 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 2018-06-13.
• Applicants must submit their applications by 2019-11-04. (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 18 828

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