Key Dates

Related Announcements

• March 19, 2021 - Notice of Special Interest (NOSI): Fundamental Science Research on Complementary and Integrative Health Approaches, Including Natural Products or Mind and Body Interventions See Notice NOT-AT-21-006. 
• May 7, 2020 - NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Required) See NOFO PA-20-194.
• May 7, 2020 - NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed). See NOFO PA-20-195. 
• May 7, 2020 - NIH Exploratory/Developmental Research Grant Program (Parent R21 Basic Experimental Studies with Humans Required). See NOFO PA-20-196. 
• May 5, 2020 - Research Project Grant (Parent R01 Clinical Trial Required)). See NOFO PA-20-183. 
• May 5, 2020 - Research Project Grant (Parent R01 Basic Experimental Studies with Humans Required). See NOFO PA-20-184.
• May 5, 2020 - NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed). See NOFO PA-20-185.

Issued by

National Center for Complementary and Integrative Health (NCCIH)

Purpose

The purpose of this Notice of Special Interest (NOSI) is to describe National Center of Complementary and Integrative Health (NCCIH) priorities in innovative basic and mechanistic research or technology/method development research relevant to complementary and integrative health approaches and their impact on health outcomes, resilience, and well-being.

Complementary health approaches include a broad range of practices and interventions that are not typically part of conventional medical care. Complementary approaches can be classified by their primary therapeutic input, which may be dietary (e.g., special diets, dietary supplements, herbs, prebiotics, and microbial-based therapies including probiotics), psychological (e.g., meditation, hypnosis, virtual reality, music-based interventions, relaxation therapies), physical (e.g., acupuncture, massage, chiropractic manipulation, light, devices related to these approaches), or a combination of psychological and physical (e.g., yoga, tai chi, dance therapies, some forms of art therapies). The dietary approaches include what have been previously categorized as natural products, whereas psychological and/or physical approaches encompass what have been commonly referred to as mind and body interventions. Integrative health brings conventional and complementary approaches together in a coordinated way. Integrative health also emphasizes multimodal interventions that aim to improve health in multiple interconnected domains, social, psychological, and physical, including multiple organs and systems.

Basic and mechanistic research on complementary and integrative health approaches should investigate the following key aspects. The first is the approach (also called intervention) itself, the second is the biological, behavioral, psychological, and/or social systems potentially targeted by the approach or intervention, and the third is the platform in which they will be studied (e.g., cell cultures, animal models, human subjects, or a computational model/in silico system). In the context of complementary and integrative health approaches, mechanistic research often refers to studies examining the interactions between the approach and the systems (e.g., biological, behavioral, psychological, and/or social), whereas basic research may investigate either the approach or intervention itself, the systems without the interactions, or the associated technologies. The scales of analysis for investigation of biological systems include biochemical, molecular, cellular, genetic, -omics (e.g., metabolomics, epigenomics, proteomics, etc.), organ systems, and behavioral. When basic research is pursued, applicants are encouraged to articulate the relevance of their basic or technological/method development research to a complementary or integrative health approach if the approach is not to be directly studied.

Although the areas of research submitted under this NOSI can be very broad, the following topics are high program priorities for NCCIH:

Basic research (Please specify the potential relevance of the proposed study to a complementary or integrative health approach if no interventions are to be studied directly.)

• Investigate the connections and interactions of multiple organ systems (e.g., any two or more physiological systems including neural, respiratory, musculoskeletal, cardiovascular, digestive, reproductive, endocrine, immune, and lymphatic, and/or host microbiome systems) in animal models or human participants. Examples of connections between physiological systems include but are not restricted to the following:
  • Nervous system and other organ system(s) connections
  • Vascular/immune system and other organ system(s) connections
  • Musculoskeletal system and other organ system(s) connections
  • Microbiome and other organ system(s) connections
  • Glymphatic system and other organ system(s) connections
• Uncover and evaluate innovative or unique mechanisms or multisystem effects that could be modulated by a complementary or integrative health approach in the context of health outcomes such as resilience, well-being, and health restoration, or in the context of ameliorating pain and associated functional impairments, sleep disturbances, stress, mild to moderate depression, eating disorders, menopause, fatigue, and other related disorders and symptoms, or in the context of disease prevention with appropriate animal models or with research participants.
• Assess unique mechanisms, factors, or potential therapeutic targets relevant to complementary or integrative health approaches.
• Identify salutogenic processes relevant for health restoration that could potentially be modulated or augmented by complementary or integrative health approaches.

Research on mechanisms of complementary and integrative health approaches

High priority areas common across complementary and integrative health approaches:

• Elucidate the mechanistic effects of a complementary or integrative health approach on multiple systems (e.g., myofascial and immune systems, neural and lymphatic systems, host microbiome system and central nervous system, endocrine and digestive systems, central nervous system and cardiovascular system or respiratory system) and the interactions among multiple systems in animal models or research participants.
• Explore the mechanistic effects of multimodal interventions or integrative health approaches (e.g., meditation and a dietary supplement, acupuncture and cannabinoids, yoga, and vagal stimulation) on one or more physiological systems and their interactions in animal models or research participants.
• Explore the mechanistic effects of complementary and integrative health approaches on salutogenic processes in animal models or research participants.
• Identify and evaluate potential biomarkers that predict the therapeutic response to a complementary or integrative health approach.
• Identify novel biological targets or innovative mechanisms of approaches in appropriate animal models or other preclinical models.
• Examine the effects of complementary or integrative health approaches on novel interoceptive processes in appropriate animal models or research participants.
• Develop and evaluate innovative (1) humanized cellular or organ systems or (2) genetically modified or preclinical animal models suitable for mechanistic studies of complementary or integrative health approaches.
• Develop and validate innovative technologies or methods to enhance and/or monitor the mechanistic effect of a complementary or integrative approach with research participants or animal models.
• Validate the scientific basis of diagnostic systems commonly used in complementary and integrative health approaches.

High priority areas of special interest to mind and body interventions:

• Ascertain the interactions of physiological (e.g., neural, musculoskeletal, immune) and psychological systems in response to force-based interventions (e.g., acupuncture, massage therapy, osteopathic manipulation, chiropractic manipulation), psychological input interventions (e.g., mindfulness, breathing, mental imagery, body scanning, hypnosis), combined physical and psychological interventions (e.g., yoga, tai chi), and music and art-based interventions in animal models or research participants.
• Investigate real-time, “online” mechanistic processes in the central nervous system and/or other physiological systems (e.g., neural, endocrine, vascular, etc.) during mind and body interventions in research participants or appropriate animal models.
• Identify shared mechanisms versus unique mechanisms among different mind and body interventions used in multimodal treatment approaches.

High priority areas of special interest to dietary input approaches, including natural products and microbial-based therapies:

• Discover novel microbial strains for microbial-based therapeutics or innovative underlying mechanisms of microbial based therapeutics for the aforementioned health outcomes.’
• Explore innovative methodological/technological approaches to improve responsiveness of microbial-based therapeutics.
• Studies examining prior human use in traditional preparations of botanicals and other natural products to enhance mechanistic understanding of natural products.
• Studies developing novel approaches for discovery of natural products targeting pain management, particularly with potential as novel nonopioid interventions.

Research on technology and tool development

High priority areas of special interest to mind and body interventions:

• Development of novel animal models or tools and technologies that may facilitate the mechanistic study of the active components of psychological and/or physical input interventions that cannot be investigated with current models and technologies.
• The development of innovative quantitative assessments of interoception processes, myofascial tissue or glymphatic/lymphatic systems in animal models or with human subjects
• Research that proposes multimodal diagnostic strategies (e.g., biochemical, structural, and biomechanical/kinematic/kinetic) to elucidate mechanistic processes.
• Non-invasive imaging techniques and related artificial intelligence/ machine learning approaches to enhance advances in modeling or identification of intervention targets and the interactions of multisystem targets.

High priority areas of special interest to dietary input approaches including natural products and microbial-based therapies:

• Develop targeted and untargeted bioinformatic approaches to identify active components in a natural product mixture.
• Develop phenotypic models capable of illuminating mechanisms of action for natural products.
• Develop and validate prognostic and diagnostic systems or devices for precision probiotic therapies.
• Develop and evaluate innovative approaches to explore biological activities of probiotics in the gastrointestinal tract.

High priority areas of special interest to whole person health and computational approaches:

• Technologies that can monitor or enhance physiological responses to complementary approaches to improve well-being and whole person health.
• The development of computational approaches and/or in-silico models to understand the effects of multicomponent interventions on complex physiological organ systems in the context of whole person health.
• The development of wearable biosensors to readout the whole-body physiological states with the integration of complementary and integrative interventions to enhance whole person health.
• The development of sensory/diagnostic devices or applications that utilize Artificial Intelligence/Machine Learning (AI/ML) to elucidate the physiological, biological, and psychological mechanisms of multicomponent interventions on whole person health promotion, restoration, and resilience.
• Development and testing of mobile health technology or nonmobile technology and methods to monitor whole person health.

Applications Not Responsive to this NOSI

• Studies exclusively focused on synthetic pharmaceuticals.
• Feasibility, efficacy, or effectiveness studies to analyze the effect size of an intervention(s) on clinical outcomes as the primary outcomes. Applicants for such studies should consult with the NCCIH Clinical Research Branch.
• Studies with a primary objective on disease treatments or pathophysiology (e.g., diabetes, arthritis, cardiovascular disease), rather than using disease models to explore innovative mechanisms of action or therapeutic biomarkers for complementary or integrative health approaches.
• Studies focusing on cancer therapeutics, treatments, or pathophysiology.
• Studies of diets, macronutrients, or micronutrients for nutritional benefits.
• Studies of the same or similar mechanistic effects of a complementary or integrative health approach as those already published in the literature in a different clinical population or using similar or related interventions are deprioritized at NCCIH.

Application and Submission Information

This notice applies to due dates on or after October 7, 2024 and subsequent receipt dates through October 18, 2027. 

Submit applications for this initiative using one of the following notice of funding opportunity (NOFO) or any reissues of these announcements through the expiration date of this notice.

• PA-20-183 - NIH Research Project Grant (Parent R01 Clinical Trial Required)
• PA-20-184 - NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)
• PA-20-185 – NIH Research Project Grant (Parent R01 Basic Experimental Studies with Humans Required)
• PA-20-194 – NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Required)
• PA-20-195 – NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed)
• PA-20-196 – NIH Exploratory/Developmental Research Grant Program (Parent R21 Basic Experimental Studies with Humans Required)   

All instructions in the SF424 (R&R) Application Guide and the notice of funding opportunity used for submission must be followed, with the following additions:

• For funding consideration, applicants must include “NOT-AT-24-041” (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B will not be considered for this initiative.

Applications nonresponsive to terms of this NOSI will not be considered for the NOSI initiative.

Inquiries

Please direct all inquiries to the contacts in Section VII of the listed notice of funding opportunity with the following additions/substitutions: