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Principal Investigator: Sudarshan R Jadcherla
Organization: RESEARCH INST NATIONWIDE CHILDREN'S HOSP
Fiscal Year: 2024
Award: $633,944
Funding agency: National Institute of Diabetes and Digestive and Kidney Diseases
PROJECT SUMMARY/ABSTRACT
The prevalence of symptom-based diagnosis of gastroesophageal reflux disease (GERD), its empiric treatment,
and practice variation in high-risk hospitalized infants remain high. Prior clinical trials data lack physiological-
based, objective diagnostic evidence and treatment. GERD is frequently diagnosed by inadequate criteria, and
the relative risks, benefits, and indications of GERD therapies are unclear. Thus, gaps in knowledge persist, and
a GERD diagnosis can cost an extra $70k and 30 days of hospitalization per infant. Objective, effective,
evidence-based therapies are critically needed. As nearly all infants in the neonatal intensive care unit (NICU)
are symptomatic, twenty-four-hour pH-Impedance (pH-Imp) testing can diagnose objectively and detect
mechanisms of pathophysiologic GERD. Therefore, this study’s overall objective is to conduct a single-center
randomized control trial (RCT) to test the central hypothesis that the effects of common therapies [natural
maturation, acid suppression-proton pump inhibitor (PPI), or thickened feeds using added rice (AR) formula] are
distinct in high-risk infants, under six months corrected maturational age with pH-Imp defined criteria for GERD.
The rationale is to refine novel diagnostic criteria and rigorously investigate the impact of randomized therapies
to achieve the long-term goal of creating effective, simplified, evidence-based, and scalable treatment
algorithms.
We will test this hypothesis in the following Specific Aims: Aim 1: Conduct the RCT to evaluate and compare the
efficacy and safety of interventions on the primary clinical endpoint (oral feeding improvement and absence of
troublesome symptoms) to test the working hypothesis that AR is superior to natural maturation and PPI. Aim 2:
Evaluate pH-Imp characteristics and test the working hypotheses that pH-Imp mechanisms are distinct between
a) assigned therapies, and b) clinical success and failure. This project challenges current empiric approaches to
diagnosing and managing GERD in NICU infants by using both a novel combination of pH-Imp metrics and
randomized allocations with targeted stratification (GERD severity and feeding skills) to determine true
therapeutic effects on clinical and mechanistic characteristics. The anticipated outcomes will identify diagnostic
algorithms for determining GERD and effective treatment approaches. In addition, the proposed research is
significant because the knowledge gained will provide the diagnostic basis, framework, and scientific and
economic rationale for future studies to further refine therapies across the pediatric age spectrum. We expect
new benchmarks to develop preventative and therapeutic strategies for GERD, which will positively impact the
quality of life for infants and parents by improving digestive health, overall nutrition, and growth, all relevant to
the mission of NIH (NIDDK).
Terms: <Acid Reflux><Acids><Active Follow-up><Adverse effects><Age><Algorithms><Benchmarking><Best Practice Analysis><Biological Markers><Caring><Categories><Cereals><Characteristics><Childhood><Chronology><Clinic Visits><Clinical><Clinical Trials><Coughing><Data><Diagnosis><Diagnostic><Diagnostic tests><Distal><Drugs><Eating><Economic Burden><Economics><Effectiveness><Electrical Impedance><Emesis><Enteral Feeding><Equilibrium><Equipoise><Esophageal Reflux><Esophagus><Evaluation><Event><Evidence based practice><Evidence based treatment><Failure><Feeding Methods><Feeds><Food Intake><Future><GERD><Gastro-oesophageal Reflux><Gastroesophageal Reflux><Gastroesophageal reflux disease><Generalized Growth><Gestation><Goals><Growth><Health><Hospital Admission><Hospitalization><Hour><Impedance><Infant><Intake><Intervention><Intervention Strategies><Investigators><Knowledge><Length of Stay><Measurement><Medication><Mission><Modification><NIDDK><NIH><National Institute of Diabetes and Digestive and Kidney Diseases><National Institutes of Health><Neonatal><Neonatal Intensive Care Units><Neurologic><Neurological><Newborn Intensive Care Units><Number of Days in Hospital><Nutrient><Oral><Outcome><Parents><Pathologic><Peripheral><Pharmaceutical Preparations><Physiologic><Physiological><Population><Pregnancy><Prevalence><Probability><Proton Pump Inhibitors><Provider><Public Health><Pump><QOL><Quality of life><Randomized><Randomized, Controlled Trials><Relative Risks><Research><Research Personnel><Researchers><Rice><Safety><Severities><Severity of illness><Stratification><Symptoms><Testing><Therapeutic><Therapeutic Effect><Time><Tissue Growth><Treatment Efficacy><Tube><United States National Institutes of Health><Variant><Variation><Vomiting><Work><active followup><ages><arm><associated symptom><balance><balance function><benchmark><bio-markers><biologic marker><biomarker><clinical efficacy><co-morbid symptom><co-occuring symptom><comorbid symptom><comparable efficacy><comparative efficacy><compare efficacy><concurrent symptom><cooccuring symptom><cost><decision making algorithm><design><designing><diagnostic algorithm><diagnostic criteria><disease diagnosis><disease severity><drug/agent><economic><effective therapy><effective treatment><efficacy testing><electric impedance><enteric feeding><evidence base><feeding><feeding tube><follow up><follow-up><followed up><followup><gastric feeding><high risk><high risk infant><hospital days><hospital length of stay><hospital re-admission><hospital readmission><hospital stay><improved><indexing><inhibitor><intervention efficacy><interventional strategy><neonatal ICU><new diagnostics><next generation diagnostics><novel><novel diagnostics><nutrition><ontogeny><parent><pediatric><primary end point><primary endpoint><primary outcome><programs><randomisation><randomization><randomized control trial><randomly assigned><re-admission><re-hospitalization><readmission><rehospitalization><response><response to therapy><response to treatment><secondary outcome><skills><socio-economic><socio-economically><socioeconomically><socioeconomics><stem><success><symptom association><symptom comorbidity><therapeutic efficacy><therapeutic response><therapy efficacy><therapy response><treatment group><treatment response><treatment responsiveness><tube feeding><unnecessary treatment><vulnerable infant>