DO BIOMARKERS PREDICT RESPONSE TO A PEDIATRIC CHRONIC PAIN SYMPTOM MANAGEMENT PROGRAM?

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Functional abdominal pain gastrointestinal disorders (FGIDs) affect 15-20% of school age children and adults in the US and worldwide. FGIDs are characterized by intermittent abdominal pain, often associated with significant disability. FGIDs continue into adulthood in up to 60% of cases and estimated costs for adults in the US are near $30 billion per year. Despite the ubiquity of FGIDs and their tremendous international economic, social, and emotional burden, finding widely effective management strategies has been elusive. Our studies in children and others in adults support cognitive behavioral therapy (CBT) as our current best strategy to treat FGIDs but abdominal pain only improves in 40% of patients. Given the expense and time investment required for CBT, the knowledge gap of which patients are likely to respond best needs to be addressed. More recently, dietary management (low FODMAP diet) is showing promise but it too, is effective in only 50% of patients. Recent studies from our group suggest that biologic factors (measured by biomarkers) play a role in determining the response to CBT. Similarly, our recent work shows that gut microbiome composition appears to influence whether abdominal pain will respond to a low FODMAP diet. Despite the potential critical importance of these highly informative physiologic biomarkers, no CBT trials to date in children or adults have measured them. Thus, building on our experience to date with CBT and dietary interventions in children with FGIDs, we propose to categorize children ages 7-12 yrs. of age with FGIDs (n=200) as to whether they have/do not have one or more of the following abnormal physiologic changes: (1) Autonomic Nervous System imbalance as measured by low heart rate variability; and/or (2) Abnormalities in gut physiology: Impaired gut barrier function (increased permeability); and/or Decreased abundance of Bacteroides (measured by shotgun metagenomic sequencing); and/or (3) Gut neuroimmune dysfunction (increased fecal chromogranin A and secretogranin 2 concentrations). We propose to randomize these children, stratified by presence/absence of physiologic abnormalities to CBT or a low FODMAP diet using our previously tested programs and compare the effectiveness of the treatments in those with/without abnormal physiologic biomarkers. We Hypothesize that CBT will be more effective in those without abnormal physiology whereas Diet will be more effective in children with abnormal physiology. Primary outcome measures will be: 1) Symptom improvement (abdominal pain frequency or severity measured by prospective diary) and 2) Improvement in health related quality of life (PedsQL) This innovative multidisciplinary study will be the first addressing the critical need to identify physiological characteristics that may moderate the response to management, potentially reducing the burden of these disorders through timely application of the intervention most likely to benefit an individual patient. The goals of this application fit with the Precision Medicine Initiative and NINR PA-16-188 and PA-14-029.