Mind and Body Interventions to Restore Whole Person Health via Emotional Well-Being Mechanisms (R61/R33 Clinical Trial Required)

The U.S. Department of Health and Human Services, through the National Institutes of Health and the National Center for Complementary and Integrative Health (NCCIH), has announced a Notice of Funding Opportunity (NOFO) titled Mind and Body Interventions to Restore Whole Person Health via Emotional Well-Being Mechanisms. This program utilizes the R61/R33 Exploratory/Developmental Phased Award mechanism and requires the inclusion of a clinical trial. The initiative aims to support mechanistic human research studies that investigate how psychological and physical practices such as mindfulness meditation, yoga, acupuncture, massage, and other body- and brain-based interventions affect mechanisms of emotional well-being (EWB) and their relationship to whole person health (WPH). The purpose of this NOFO is to address the NIH priority of improving the health and well-being of Americans by studying the pathways through which mind and body interventions may influence emotional states and overall health outcomes. The studies funded under this opportunity must focus on innovative mechanisms of EWB as primary outcomes, while including the Whole Person Health Index (WPHI) as a secondary measure. The WPHI was developed in collaboration with the Centers for Disease Control and Prevention and assesses domains such as quality of life, physical activity, social connections, stress management, sleep, and sense of purpose. This initiative recognizes the widespread use of complementary health approaches in the United States and seeks to fill gaps in rigorous scientific understanding of their effects on well-being and health restoration. Funding is structured in two phases. The R61 phase, lasting up to two years, focuses on demonstrating feasibility benchmarks including participant recruitment, retention, adherence to interventions, and the collection of mechanistic outcomes. Transition to the R33 phase, which may last up to four years, is contingent upon meeting predefined “Go/No-Go” criteria. The R33 phase will support completion of a fully powered mechanistic clinical trial. Importantly, these trials are not intended to evaluate intervention efficacy or effectiveness but instead to clarify mechanisms of action underlying EWB and WPH. Randomized controlled trial designs with comparator or control groups are required, and rigorous standards for masking, blinding, and methodological clarity must be maintained. The NCCIH anticipates committing $2,000,000 in FY 2026 to fund approximately three awards. Individual applications may request budgets of up to $475,000 per year in direct costs, and total project periods may not exceed five years across both phases. No cost sharing or matching requirement applies. All applications must be submitted electronically through Grants.gov and tracked in the NIH eRA Commons system. Applicants are required to follow the Research (R) Instructions in the NIH Application Guide and to provide a Data Management and Sharing Plan. Eligibility is broad and includes higher education institutions (public and private), nonprofits with or without 501(c)(3) status, for-profit organizations (including small businesses), local and state governments, tribal governments and organizations, independent school districts, public housing authorities, faith-based and community-based organizations, and regional organizations. Foreign organizations are not eligible to apply, and foreign components of U.S. organizations are also excluded. Program directors and principal investigators must have eRA Commons accounts and demonstrate the skills and resources needed to conduct the proposed research. Applications will be accepted in multiple cycles, beginning with the first deadline on November 7, 2025. Subsequent deadlines occur February 9, 2026; June 8, 2026; October 7, 2026; February 8, 2027; June 8, 2027; October 7, 2027; February 8, 2028; and June 7, 2028. Applications are due by 5:00 PM local time of the applicant organization. Scientific merit review will follow each deadline, with advisory council review and earliest start dates approximately six to nine months thereafter. The funding opportunity will expire on June 8, 2028. For assistance, applicants may contact Dr. Erin Burke Quinlan at NCCIH for scientific and research inquiries (erin.quinlan@nih.gov, 301-451-0636), Debbie Chen for grants and financial management questions (debbie.chen@nih.gov, 301-594-3788), or the NIH eRA Service Desk and Grants.gov support for technical submission issues. Peer review contacts will be assigned after application submission in eRA Commons. This NOFO is authorized under Sections 301 and 405 of the Public Health Service Act and adheres to NIH and federal grants policy requirements.