NCCIH Natural Product Early Phase Clinical Trial Phased Innovation Award (R61/R33 Clinical Trial Required)
Funds early-stage clinical trials of promising natural products (botanicals, probiotics, supplements) to assess their effects and optimize their use for potential health benefits.
This grant is no longer accepting proposals
National Institutes of Health has archived this opportunity.
Funder: National Institutes of Health (NIH)
Due Dates: March 4, 2024 | October 21, 2024 | June 23, 2025 | February 23, 2026 | October 20, 2026
Funding Amounts: Up to $350,000 direct costs per year for up to 3 years (R61 phase) plus up to 3 years (R33 phase), total up to 5 years.
Summary: Supports early phase clinical trials of natural products to test target engagement and optimize dosing, with a phased R61/R33 mechanism requiring clinical trials.
Key Information: Requires a Plan for Enhancing Diverse Perspectives (PEDP); only supports trials of natural products with strong scientific premise; no efficacy or cancer prevention/treatment trials; transition to R33 contingent on R61 milestones.
Description
This funding opportunity from the National Center for Complementary and Integrative Health (NCCIH) at NIH supports investigator-initiated, early phase clinical trials of natural products, including botanicals, probiotics, and dietary supplements with a strong scientific rationale. The goal is to rigorously test whether these natural products engage their biological targets in humans and to optimize their use before proceeding to larger efficacy trials.
The award uses a phased R61/R33 mechanism:
-
R61 Phase (up to 3 years): Milestone-driven studies to test pharmacokinetics (PK), bioavailability, safety, and target engagement of the natural product in humans. Placebo controls are required to confirm effects are due to the product. Applicants must define clear Go/No-Go criteria for progression to the R33 phase, including quantitative thresholds for target engagement and safety/tolerability metrics.
-
R33 Phase (up to 3 years): Contingent on successful R61 milestones, this phase aims to replicate target engagement findings and assess associations between target engagement and clinical or functional outcomes. It may also include dose optimization, combination treatments, or studies in more responsive populations.
This mechanism is intended to accelerate translation of basic science findings into early-stage clinical testing. It does not support efficacy or effectiveness trials, nor trials for cancer treatment or prevention.
Applicants must propose a natural product with compelling preliminary evidence and a clear scientific premise. The natural product must be well-characterized, and if required, an IND or IDE must be in place before award. The trial design should be randomized and placebo-controlled; wait-list controls are not supported.
A Plan for Enhancing Diverse Perspectives (PEDP) is required and will be evaluated during peer review and programmatic review.
Key Features
- Focus on target engagement (mechanism of action) rather than clinical efficacy in the R61 phase.
- Milestone-driven with explicit Go/No-Go criteria.
- Up to 5 years total support (R61 + R33).
- Supports optimization of dose, formulation, and population responsiveness.
- Requires rigorous clinical trial design with placebo or active comparator.
- Excludes trials of synthetic derivatives, cancer treatment/prevention, or non-natural products.
- Encourages early consultation with NCCIH scientific staff.
- Requires compliance with FDA and other regulatory requirements.
- Requires inclusion of diverse populations and a PEDP.
