Posted: March 13, 2020

Letter of Intent due 30 days prior to application; Application due July 9, 2020

This FOA will support mechanistic investigation of glymphatic, meningeal lymphatic, and/or peripheral lymphatic functions modulated by complementary and integrative health approaches. Studies that explore the mechanisms by which natural products (such as botanicals, prebiotics/probiotics, naturally-derived peptides/lipids, dietary supplements, and special diets) and mind-body approaches (such as acupuncture, chiropractic/cranial massage, exercise, meditation, yoga breathing, tai chi, qigong, yoga, hypnosis, transcranial magnetic or electric stimulation, light or auditory tone stimulation) alone or in combination with conventional medical interventions such as pharmacological or surgical interventions, modulate glymphatic, meningeal lymphatic, and/or peripheral lymphatic functions, are strongly encouraged.

Topics of interest relevant to this initiative include, but are not limited to, the following:

  • Physiological, biomechanical, biological, immunological, and/or neurological mechanisms by which complementary and integrative health approaches may regulate glymphatic and/or lymphatic functions: for example, changes of arousal state, neurotransmitters, neuronal excitability, astrocytic AQP4 polarization, VEGF-C/VEGF-R3 activity, CSF circulation, interstitial convective flow and pressure, etc.
  • The impact of complementary and integrative health approaches on glymphatic and/or lymphatic functions or the interactions between glymphatic/lymphatic functions and physiological/pathological processes relevant to health and disease conditions, such as:
    • Central and peripheral pain processes in chronic pain conditions and the transition from acute to chronic pain: for example, how these approaches affect the regulation of astrocytosis/gliosis, central proinflammatory cytokines, chemokines, neuromodulators, and immune cell and immunomodulator trafficking.
    • Symptoms and conditions related to mental health (i.e. anxiety, stress, depression, emotion dysregulation, attention deficit, insomnia), and executive dysfunction or cognitive decline: for example, studies of how these approaches affect clearance of neural toxic waste products or neuroinflammatory factors, senescence-associated secretome components, or regulation of immune cell/immunomodulatory trafficking and immune surveillance.
    • Cognitive, emotional, and behavioral resilience, health and well-being: for example, how these approaches may affect the modulation of tissue microenvironment and neuroimmune function.
  • Development and/or optimization of complementary and integrative health approaches in animal models or with human research participants to identify relevant intervention components that facilitate modulation of glymphatic and/or meningeal lymphatic functions.

The participating ICs encourage basic science and mechanistic clinical researchers to submit exploratory applications in response to this FOA.

For clinical trial, this FOA will support clinical trials of complementary and integrative health approaches in which the primary outcomes are mechanistic. Applications should not include any specific aims that propose to measure efficacy or effectiveness of any intervention (e.g., effect size assessment of the clinical outcomes). However, clinical endpoints may be measured as secondary outcomes for association analysis or as primary outcomes to establish biomarker metrics through predictive analysis. Investigators who wish to conduct studies with efficacy or effectiveness of clinical endpoints in the mission of NCCIH should consider other NCCIH-issued FOAs described on the NCCIH website:

Applications that propose the following will be considered non-responsive and will be administratively withdrawn without peer review:

  • Studies that exclusively employ conventional medical interventions such as drugs, radiation or surgery without a complementary and integrative health approach
  • Studies that don't include complementary and integrative health approach in one or more specific aims of an application
  • Clinical trials designed to measure the efficacy or effectiveness of complementary and integrative health approaches on clinical outcomes as a specific aim

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