Clinical Coordinating Center for NCCIH Multi-Site Investigator-Initiated Clinical Trials of Natural Products (Collaborative UG3/UH3 Clinical Trial Required)

The Department of Health and Human Services’ National Center for Complementary and Integrative Health (NCCIH), through the National Institutes of Health (NIH), has reissued a funding opportunity announcement (FOA) under PAR-24-312. This opportunity invites applications for a Clinical Coordinating Center (CCC) for multi-site, investigator-initiated Phase III and later-stage clinical trials investigating the efficacy of natural products in treating health conditions prioritized by the NCCIH. These natural products include botanicals, probiotics, and standardized nutritional supplements with preliminary evidence of health benefits. The CCC will be responsible for the design, management, and execution of a clinical trial across multiple sites, while a companion Data Coordinating Center (DCC), applied for separately under PAR-24-313, will manage data coordination and analysis, as well as overall trial integrity. The FOA’s primary aim is to advance the scientific understanding of complementary health products through rigorous, well-powered trials. By requiring collaboration between the CCC and DCC, NCCIH ensures that trials are conducted with scientific rigor, including validated methodologies for target engagement and a clear hypothesis about the product’s mechanism of action. Eligible trials must aim to produce high-quality evidence on clinical efficacy, with designs allowing for broad generalizability across different populations. Topics of high priority include natural products for managing symptoms like pain, sleep disorders, gastrointestinal issues, mental health conditions, post-COVID conditions, and conditions impacting minority health. Applications must be structured around a two-phase funding mechanism, UG3 for planning and UH3 for trial execution. The UG3 phase is intended for planning activities, such as obtaining regulatory approvals and developing trial infrastructure. Upon meeting specific milestones, the project may advance to the UH3 phase, which covers full participant recruitment and trial implementation. Both phases are funded under a cooperative agreement model, meaning NIH will provide substantial scientific guidance. The UH3 phase may extend up to four years, or six with strong justification. Eligible applicants include higher education institutions, nonprofits, small businesses, local governments, and tribal entities. The application process requires completing various registrations, including the System for Award Management (SAM) and NIH’s eRA Commons. Applications must reflect the actual project costs, with budgets exceeding $500,000 in direct costs subject to additional review. Applications must include a “Plan for Enhancing Diverse Perspectives (PEDP),” emphasizing inclusivity and diversity in research perspectives and the participant pool, which will be reviewed as part of the application’s scientific merit. Submissions are due by 5:00 PM local time on February 20, 2025, with subsequent deadlines on June 23, 2025, and in 2026, contingent upon the timing of scientific merit reviews and advisory council approvals. The earliest anticipated start date for funded projects is December 2025, following the advisory council’s final review. For application submission, applicants should use the SF424 (R&R) form and adhere to NIH’s updated FORMS-I application package, which will be available before the earliest submission date. Applications must comply strictly with the Research Instructions Guide and FOA-specific guidelines to avoid delays or rejections. Submission platforms include NIH ASSIST, Grants.gov, or other institutional systems. The CCC application must clearly outline a project management plan and strategy for achieving milestones, addressing barriers, and managing risks. Inquiries about the application process or eligibility requirements can be directed to NCCIH program staff, and prospective applicants are encouraged to consult with an NCCIH program officer before submission to clarify scope and goals.