The purpose of this Notice of Funding Opportunity (NOFO) is to support trans-disciplinary, translational research on chemically complex botanical products or natural products traditionally used as dietary components, to inform future clinical trials of the efficacy of exceptionally promising dietary supplements for improving resilience. Clinical efficacy trials of such products are often challenged by gaps in understanding that critically affect the design and/or interpretation of a clinical trial. For example, the molecular mechanism(s) of action of a botanical dietary supplement might not be well established and thus the optimal product chemistry, for a given health outcome may not be known; in the absence of such information to guide product specifications, stability testing and assessments of bioavailability and absorption kinetics a clinical trial might not provide a good test of the effect of that botanical on the health outcome(s) assessed. Similarly, the best outcome measure for a trial of a product reputed to have many different health effects, or to have effects where many different quantitative outcomes might be relevant might benefit from deeper understanding of the biological structure(s) and/or system(s) affected by the product, and the health outcomes expected from modulating those targets. Interpretation of a clinical trial of an ingested product will benefit from the availability of methods to assess bioavailability of active constituents of the product or target engagement by those constituents. Clinical trial design will benefit from an understanding of the ways in which trial participant characteristics, whether genetics, background diet, epigenomics, gut microbiota, or health history, for example, may influence the effect of the intervention tested. The forgoing are examples of the types of knowledge gaps of interest for this NOFO.
The overarching goal of this NOFO is to address those knowledge gaps most critical to the optimal design or interpretation of a future randomized clinical trial (RCT). Knowledge gaps to be addressed may include, but are not limited to those cited above, and should depend on the product and outcomes to be studied and the extent and strength of prior, relevant evidence. The RM1 is intended to support research that requires the capabilities of multiple laboratories working together as equal contributors on a single over-arching set of integrated specific aims. Projects proposed in response to this NOFO, therefore, must require dynamic, synergistic interactions among a range of experts to address the proposed specific aims while ensuring rigor in all aspects of this research. These trans-disciplinary projects must be supported by multi-PD/PI (Program Director/Principal Investigator) teams. Plans for enhancing workforce and institutional capacity to conduct future rigorous, trans-disciplinary research on chemically complex natural products must be built into the research plans. Achievement of the RM1 specific aims is expected to provide a strong foundation for future trans-disciplinary research on botanical natural products and for a future highly informative clinical efficacy trial of the effects on resilience of a chemically complex natural product.
This NOFO is part of the Consortium Advancing Research on Botanicals and Other Natural Products (CARBON) Program. Other elements of this Consortium include RFA-AT-24-008, Leveraging Data at Scale to Understand Natural Product Impacts on Whole Person Health and RFA-AT-24-007, Limited Competition: Research Resource for Natural Product Nuclear Magnetic Resonance Data.