NCCIH Natural Product Phase II Clinical Trial Cooperative Agreement (U01) | PAR 17 216

FAQs - NCCIH Natural Product Phase II Clinical Trial Cooperative Agreement (U01) (PAR-17-216)

What is this funding opportunity?

This opportunity is the NCCIH Natural Product Phase II Clinical Trial Cooperative Agreement (U01), Funding Opportunity Number PAR-17-216. It is a National Institutes of Health (NIH) grant opportunity administered by the National Center for Complementary and Integrative Health (NCCIH) to support investigator-initiated Phase II clinical trials of natural products for specific health-related outcomes.

What kind of studies does the FOA support?

The FOA supports Phase II clinical trials that test natural products for clinically meaningful health outcomes. Trials are expected to be well-controlled and designed to evaluate effects on symptoms and conditions where natural products are commonly used or show promise.

Which symptoms or conditions are emphasized?

The FOA highlights clinically meaningful symptoms and conditions including sleep disturbance, pain conditions, and selected mental health concerns such as mild to moderate depression, anxiety, and post-traumatic stress.

Does the FOA encourage microbiome-related research?

Yes. In addition to symptom-focused trials, the FOA encourages studies of probiotics and other natural products that examine gut-microbiome interactions with the brain and/or the immune system, reflecting interest in pathways that may influence behavior, mood, stress responses, inflammation, and other physiologic processes.

Is this FOA meant for early exploratory or high-uncertainty ideas?

No. A defining feature of this FOA is that it is not intended for early exploratory concepts without groundwork. Applications are expected to have sufficient preliminary data supporting the rationale and feasibility for a Phase II clinical trial.

What preliminary data are applicants expected to provide?

Applications must be backed by sufficient preliminary data demonstrating bioavailability, meaning evidence that the natural product (or its relevant constituents) can be absorbed and present in the body in a way that makes a therapeutic effect plausible.

What does the FOA mean by "bioavailability" in this context?

In this FOA, bioavailability refers to evidence that the natural product (or relevant constituents) can be absorbed and present in the body in a way that supports the plausibility of a therapeutic effect.

What is meant by a "replicable and measurable biological signature"?

Applicants are expected, whenever possible or practical, to document that the natural product produces a replicable and measurable biological signature that is relevant to the proposed patient population. This could be a biomarker, physiologic response, microbiome pattern, immune change, neurobehavioral signal, or another measurable indicator that can be observed repeatedly and supports the proposed mechanism of action.

Why does the FOA emphasize biological signatures and mechanism-related measures?

The emphasis is intended to strengthen interpretability of trial results, reduce the chance of ambiguous outcomes, and improve the scientific value of Phase II testing by linking clinical endpoints to measurable biology.

What is the funding mechanism, and why does it matter?

The funding mechanism is a cooperative agreement (U01). This generally means there is substantial scientific or programmatic involvement by NIH staff compared with a standard research project grant, even though investigators still propose and lead their trials.

How might NCCIH be involved under a U01 cooperative agreement?

Under the cooperative structure, NCCIH may participate in areas such as coordinating expectations for study milestones, advising on trial conduct and oversight, and ensuring alignment with program priorities and clinical trial standards.

What is the activity category for this opportunity?

The activity category is Health.

What CFDA number is associated with this opportunity?

The CFDA number associated with this opportunity is 93.213.

When was this opportunity created and when did it close?

The listing indicates the opportunity was created on March 10, 2017, and the original closing date was January 24, 2018.

Is this opportunity discretionary funding?

Yes. The opportunity is categorized as discretionary funding.

Does the public listing specify an award ceiling or the expected number of awards?

No. The public listing does not specify an award ceiling or the expected number of awards.

Where would applicants normally look for budget limits and project period expectations?

Because the listing does not include an award ceiling or number of awards, applicants would normally consult the full FOA and NIH budget guidance to understand allowable costs, expected project period, and any institute-specific limits.

Who is eligible to apply?

Eligibility is broad and includes many types of domestic organizations capable of conducting clinical trials, including various government entities, institutions of higher education (public and private), tribal governments and tribal organizations, public housing authorities/Indian housing authorities, nonprofits (with and without 501(c)(3) status, other than institutions of higher education), for-profit organizations (other than small businesses), small businesses, and other eligible entities.

Are state and local government entities eligible?

Yes. Eligible applicants include state governments, county governments, city or township governments, special district governments, and independent school districts.

Are colleges and universities eligible?

Yes. Public and state-controlled institutions of higher education and private institutions of higher education are eligible.

Are tribal entities eligible?

Yes. Federally recognized Native American tribal governments and tribal organizations that are not federally recognized are included in the eligibility list.

Are nonprofits eligible?

Yes. Nonprofits with 501(c)(3) status (other than institutions of higher education) and nonprofits without 501(c)(3) status (other than institutions of higher education) are eligible.

Are for-profit organizations eligible?

Yes. For-profit organizations other than small businesses are eligible, and small businesses are also listed as eligible applicants.

Are U.S. territories or possessions eligible?

Yes. The FOA explicitly highlights U.S. territories or possessions among eligible applicant categories.

Does the FOA highlight any specific institution types as eligible?

Yes. The FOA highlights Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISI), Hispanic-serving Institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), and faith-based or community-based organizations as additional eligible categories.

Are federal government agencies eligible to apply?

Yes. The FOA highlights eligible federal government agencies among eligible applicant categories.

Can non-U.S. (foreign) organizations apply?

No. Non-domestic (non-U.S.) entities are not eligible to apply, and non-domestic components of U.S. organizations are also not eligible to apply as the applicant organization.

Are foreign collaborations allowed at all?

Yes, foreign components are allowed as defined in the NIH Grants Policy Statement. A U.S. applicant may include certain foreign collaborations or performance sites if they meet NIH rules, are scientifically justified, and comply with NIH policy, but the applicant organization itself must be domestic.

What is the overall goal of this FOA?

The FOA is aimed at moving natural product research into rigorous, mid-stage (Phase II) clinical testing where there is already credible evidence the product can reach the body (bioavailability) and produces measurable biologic effects tied to a hypothesized mechanism. It is particularly relevant for teams prepared to pair patient-centered outcomes (such as pain, sleep, mood, or stress-related symptoms) with objective mechanistic or biomarker-based measures, including microbiome-immune-brain interaction readouts when probiotics or related products are involved.