(CLOSED) Pediatric Obesity Discovery Science Research to Improve Understanding of Risk and Causal Mechanisms for Obesity in Early Life (R01 Clinical Trial Optional) (RFA-DK-21-025)

The purpose of this Funding Opportunity Announcement (FOA) is to support innovative, discovery research studies to better characterize early-life risk factors and elucidate underlying causal mechanisms through which these risk factors contribute to the development of obesity during infancy and early childhood. Studies should aim to understand biological mechanisms that mediate behavioral and/or metabolic risk for obesity development in young children and how risk may be modified by other contributors such as psychosocial, contextual, and/or environmental factors. Projects should be designed to study infants and children longitudinally and at frequent intervals during the first 3 years of life to explore potential determinants and mechanisms for the development of obesity. Studies may examine predictive measures from the pre-conceptional period to birth but must include longitudinal data of the infant from birth to 3 years of life. Proposed studies ancillary to ongoing parent studies with a cohort of well-characterized participants (pregnant women and infants) and existing research infrastructure that leverage use of data and biological samples are acceptable. Examining trajectories of change in BMI and fat mass over time as well as the development of obesity defined as a categorical outcome is encouraged.

Discovery tools measuring biological factors such as multi-omics (metabolomics, proteomics, transcriptomics), epigenetics, genomics, extracellular vesicles or nutrient signaling factors can provide novel insights into the causes of obesity. These factors can be integrated by a systems biology approach or through pathway analyses and can offer opportunities to better understand underlying biological mechanisms. Biospecimens in infants and children, including blood, urine, stool, and/or saliva should be collected for discovery-oriented analyses. Collection of other biospecimens, including but not limited to maternal blood, paternal sperm, cord blood, placenta and/or breast milk may be proposed as relevant to the study objectives. The proposed assessments should be scientifically robust whether they be clinical, metabolic, neurocognitive, behavioral measures, or approaches to capture social determinants of health.

Studies are strongly encouraged to include short mechanistic interventions (perturbations or challenge studies) where relevant to provide support for hypothesized causal relationships, but interventions with a goal of obesity prevention or treatment are non-responsive to this FOA. Studies are expected to be largely hypothesis generating but sample size must be justified. Subsequent larger, independent studies would follow and be necessary to validate findings.

Projects that seek to enroll diverse populations at high risk for obesity and health disparities such as racial and ethnic minority populations, less privileged socioeconomic status (SES) populations, underserved rural populations, and any subpopulations that can be characterized by two or more of these descriptions are particularly encouraged. Social determinants of health—the conditions in which people are born, grow, live, work and age—are also known to drive health disparities including the development of obesity; therefore, applicants are strongly encouraged to collect and integrate the measures from the Core and relevant Specialty collections available in the Social Determinants of Health Collections of the PhenX Toolkit (www.phenxtoolkit.org) whenever possible.