Exploring the Mechanisms Underlying Modulation of Glymphatic-Lymphatic Systems by Complementary and Integrative Health Approaches (R21 Clinical Trial Optional) | RFA AT 21 002

Opportunity Information: Apply for RFA AT 21 002

The NIH funding opportunity "Exploring the Mechanisms Underlying Modulation of Glymphatic-Lymphatic Systems by Complementary and Integrative Health Approaches (R21 Clinical Trial Optional)" (RFA-AT-21-002) supports early-stage, exploratory research aimed at understanding how complementary and integrative health approaches influence the body’s glymphatic and lymphatic systems. The central focus is on mechanism: applicants are expected to move beyond simply observing changes and instead test biologically plausible pathways explaining how and why these approaches might alter glymphatic-lymphatic activity, or how they change the relationship between these clearance/immune-transport systems and broader physiological or disease-related processes.

Projects under this FOA are intended to examine either (1) the impact of complementary and integrative health approaches on glymphatic and/or lymphatic function, or (2) how these approaches modify interactions between glymphatic/lymphatic function and physiological or pathological states. In practical terms, that can include studies looking at how an intervention affects fluid clearance, immune trafficking, neuroinflammation, waste removal in the brain, or related functional dynamics, as well as how these changes connect to normal body regulation or to disease mechanisms. The announcement is flexible about the experimental setting, allowing mechanistic work in relevant animal models and/or in human research participants, as long as the application stays anchored to mechanistic discovery rather than clinical endpoint testing.

Although the FOA is labeled "Clinical Trial Optional," it draws a clear boundary around what kinds of human studies it will and will not support. It does not fund clinical trials designed primarily to test efficacy or effectiveness on clinical outcomes (for example, a trial whose main goal is to show that an intervention improves a patient-reported symptom or reduces disease incidence). Human studies may be included when they are designed to interrogate mechanism, such as measuring physiological, imaging, biomarker, or functional readouts that illuminate glymphatic-lymphatic modulation. In other words, if an intervention is used in people, the purpose should be to understand biological processes and system-level interactions, not to make a definitive claim about therapeutic benefit.

The funding mechanism is an NIH R21, which is generally used for exploratory and developmental projects where the goal is to generate foundational mechanistic evidence, develop new lines of inquiry, or produce preliminary data that can justify larger subsequent studies. The listed award ceiling is $200,000, indicating that proposed projects should be appropriately scoped for a smaller, hypothesis-driven mechanistic effort rather than an expansive multi-site clinical program. The opportunity is categorized as a discretionary grant within NIH’s health research mission areas and is associated with CFDA numbers 93.121 and 93.213.

Eligibility is broad and includes many types of U.S.-based organizations and governmental entities. Eligible applicants include state, county, city/township, and special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; federally recognized Native American tribal governments and other 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); and small businesses. The FOA explicitly highlights additional eligible applicant categories such as Historically Black Colleges and Universities (HBCUs), Hispanic-serving institutions, Tribally Controlled Colleges and Universities (TCCUs), Alaska Native and Native Hawaiian Serving Institutions, and Asian American Native American Pacific Islander Serving Institutions (AANAPISIs), as well as faith-based or community-based organizations, eligible federal agencies, regional organizations, and U.S. territories or possessions.

At the same time, the FOA sets important limits on foreign participation. Non-domestic (non-U.S.) entities (foreign organizations/institutions) are not eligible to apply as applicant organizations, and non-domestic components of U.S. organizations are also not eligible to apply. However, foreign components are allowed under NIH policy as defined in the NIH Grants Policy Statement, meaning the project can include certain international elements (for example, specialized analyses, unique resources, or collaborations) when they meet NIH’s definition and justification requirements, even though the primary applicant organization must be domestic.

Key administrative details from the provided source include an original closing date of July 9, 2020, and a creation date of March 5, 2020. The sponsoring agency is the National Institutes of Health. Overall, the opportunity is best suited to research teams proposing tightly designed mechanistic studies that connect complementary and integrative health approaches to measurable changes in glymphatic and lymphatic biology, especially where the work can clarify underlying pathways or system interactions rather than simply demonstrating a clinical effect.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Exploring the Mechanisms Underlying Modulation of Glymphatic-Lymphatic Systems by Complementary and Integrative Health Approaches (R21 Clinical Trial Optional)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.121, 93.213.
• This funding opportunity was created on 2020-03-05.
• Applicants must submit their applications by 2020-07-09. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Each selected applicant is eligible to receive up to $200,000.00 in funding.
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

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