Advancing Clinical Science in Pediatric Gastroparesis

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Gastroparesis (GP) in children and adults is characterized by delayed gastric emptying in the absence of mechanical obstruction. GP is associated with significant morbidity and mortality yet little is known regarding its incidence, prevalence, and natural history, particularly in children. This knowledge gap in pediatric GP is exacerbated by lack of both normative data for gastric emptying and a GP specific patient reported outcome measure. The limited data suggest significant differences between clinical symptoms of GP in children vs adults. Thus, even the limited data regarding GP in adults are unlikely to provide insight and fill the knowledge gaps regarding GP in children. These issues (among others) underscore the need for childhood GP specific research strategies rather than translation of adult based GP knowledge to this very different population. To begin to identify effective diagnostic and therapeutic strategies leading to improved outcomes for children with GP given the vast knowledge gaps in the field, we propose the following Specific Aims within a prospective, multiinstitutional collaboration: 1) Using the 13C-Spirulina breath test (BT) (which correlates well with gastric scintigraphy) define normal values for solid meal emptying in (n=260) healthy controls (HC) (5-18 yrs. of age). Sub-Aim: carry out the BT in children (n=420, 5-18 yrs. of age) with presumed GP who are undergoing gastric scintigraphy to identify children who truly have GP as defined by the normal values obtained in HC. 2) In children undergoing gastric scintigraphy in (Sub) Aim 1, determine the feasibility, reliability, and validity of generic and gastrointestinal (GI)-specific health-related quality of life using the Pediatric Quality of Life Inventory (PedsQL) Generic Core Scales and PedsQL GI Symptoms Scales and PedsQL GI Worry Scales. Sub- Aim 2A: Use the scales to differentiate patients with GP vs. age, gender, and race/ethnicity matched children with functional dyspepsia (whose symptoms often overlap with GP) and HC; Sub-Aim 2B: Use the GI scales and cognitive interviews to create a pediatric GP-specific health-related quality of life measure. 3) Create a national prospective: (a) Registry of children and adolescents with GP to include demographic, clinical, psychological, and nutritional characteristics and (b) Biorepository of serum, GI mucosal biopsies (in those undergoing upper GI endoscopy), and stool for future analyses such as DNA, cytokines, microbiome. This multidisciplinary approach is innovative as it will, for the first time, prospectively begin to fill the vast knowledge void regarding GP in children. These data will be an important step toward targeted and pediatric- friendly interventions for children with GP. This project also will be a first step to developing a national pediatric consortium to investigate GP in children. The current proposal fits RFA-DK-16-010 to, among other goals, better understand the epidemiology of GP, define the GP/FD spectrum, explore and design new patient reported outcomes, and the role of the human microbiome on disease expression.