NCCIH Natural Product Phase II Clinical Trial Cooperative Agreement (U01 Clinical Trial Required) | PAR 18 125

Opportunity Information: Apply for PAR 18 125

The NCCIH Natural Product Phase II Clinical Trial Cooperative Agreement (U01 Clinical Trial Required), PAR-18-125, is a National Institutes of Health funding opportunity from the National Center for Complementary and Integrative Health (NCCIH) designed to support investigator-initiated Phase II clinical trials that test natural products in humans. The main purpose is to evaluate whether specific natural products can help treat or improve clinical symptoms in areas where patients commonly seek complementary approaches, including sleep disturbance, pain-related conditions, and certain mental health concerns such as mild to moderate depression, anxiety, and post-traumatic stress. In addition to symptom-focused trials, the announcement also encourages studies that examine probiotics or other natural products for their effects on gut microbiome interactions with the brain and/or the immune system, reflecting growing scientific interest in microbiome-linked mechanisms.

A defining feature of this FOA is that NCCIH is not looking for early-stage, exploratory clinical work without strong grounding. Applications must include adequate preliminary evidence that the natural product is bioavailable, meaning it can be absorbed and reach relevant biological compartments in a way that makes a clinical effect plausible. Alongside bioavailability, the applicant must document that the product produces a replicable and measurable biological signature whenever it is possible or practical to measure one. In other words, the trial should be anchored to a credible, testable mechanism of action or mechanistic pathway, supported by objective measures that can be reproduced. The FOA also emphasizes that the natural product should be relevant to, and used by, the patient population under study, keeping the research tied to real-world patterns of use rather than purely theoretical interest.

The award mechanism is a cooperative agreement (U01), which generally means NCCIH expects to have substantial scientific and programmatic involvement during the conduct of the project compared to a standard research grant. This typically aligns with more complex clinical trial expectations, including careful attention to trial operations, quality control, and well-defined milestone-driven progress. The activity category is Health, and the CFDA number listed is 93.213. The opportunity is categorized as discretionary funding.

Eligibility is broad and includes many types of U.S.-based organizations and government entities. Eligible applicants include state, county, city or township, and special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; federally recognized Native American tribal governments; tribal organizations that are not federally recognized; public housing authorities/Indian housing authorities; nonprofits with or without 501(c)(3) status (as long as they are not institutions of higher education); for-profit organizations other than small businesses; small businesses; and other organizations that meet NIH eligibility requirements. The FOA also explicitly highlights additional eligible groups such as Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISIs), faith-based or community-based organizations, Hispanic-serving institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), regional organizations, eligible federal agencies, and U.S. territories or possessions.

At the same time, the FOA draws clear boundaries around foreign participation. Non-domestic (non-U.S.) entities (foreign institutions) are not eligible to apply as applicants, 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 typically means a U.S. applicant can include certain well-justified foreign collaborations or activities as part of the project when permitted under NIH policy.

The source data indicates the FOA was created on 2017-11-30, with an original closing date of 2019-11-04. An award ceiling and expected number of awards are not specified in the provided listing. Overall, the opportunity targets well-prepared Phase II natural product clinical trials that can connect patient-relevant outcomes to measurable biology, strengthening the likelihood that results will be interpretable, reproducible, and useful for future research and clinical decision-making.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "NCCIH Natural Product Phase II Clinical Trial 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): 93.213.
• This funding opportunity was created on 2017-11-30.
• 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.)
• 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 18 125

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