Neonatal Gastro-Esophageal Reflux Disease (GERD) Management Trial

Study Overview
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Brief Summary
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The overall purpose of the investigator's study is to evaluate the causes of and treatment for feeding difficulty in infants with Gastro-esophageal Reflux Disease (GERD). New treatments can be possible only if the cause is known. Many infants have GERD and feeding difficulties, such as sucking and swallowing problems, vomiting, or delayed emptying of the stomach. Some of these infants have difficulty in protecting their airway during feeding or during reflux, and as a result can breathe fluid into their lungs or hold their breath. Most GERD treatments are done based on experience, but there is no scientific proof that these methods work for infants. GERD and feeding difficulties can lead to longer hospitalization and more stress for the family. In this clinical trial, the investigators are developing new methods to help with diagnosis as well as defining better treatment strategies in relieving GERD and GERD complications.

Detailed Description
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Gastroesophageal reflux disease (GERD) and its troublesome complications constitute serious diagnostic and management challenges to the development of safe feeding and airway protection strategies among infants convalescing in the neonatal intensive care units; thus contributing to prolonged lengths of stay, recurrent hospitalizations, and death. GERD is frequently diagnosed by inadequate criteria, and the relative risks, benefits and indications of GERD therapies are unclear. Significant gaps in knowledge exist in understanding the complex causal or adaptive aerodigestive protective reflex mechanisms implicated in GERD in infants. The long-term goal is to improve digestive health, nutrition, and infant development through the design of simplified personalized treatment paradigms by better understanding the pathophysiology of aerodigestive reflexes. The current objective is to conduct a prospective single center randomized blinded controlled trial comparing the short term effects of the investigators innovative feeding strategy bundle (study approach) versus standard feeding approach (conventional approach).

Official Title
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Pathophysiology of the Aerodigestive Reflex in Infants: GERD Management Trial

Conditions
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Gastroesophageal Reflux Disease

Intervention / Treatment
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* Other: Study Arm - acid suppression plus feeding bundle
* Other: Conventional arm - acid suppression only


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Hospitalized infants with aerodigestive or GERD symptoms Gestational age ≤42 weeks Premature infants are eligible at 34 weeks postmenstrual age (PMA) Enteral or Oral Fed Average daily total feeding volume ≥ 150ml/kg/day Room air or supplemental oxygen of ≤1 liter/minute (LPM) and/or ≤ 35% by nasal cannula Exclusion Criteria: Known genetic, metabolic or syndromic disease Neurological diseases such as Grade 3 or 4 intraventricular hemorrhage (IVH) or intracranial hemorrhage (ICH) and perinatal asphyxia Gastrointestinal malformations and surgical gastrointestinal conditions

Ages Eligible for Study
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Minimum Age: 34 Weeks
Maximum Age: 60 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study<br>Treated with omeprazole. This group of subjects will have prescribed restricted feeding volumes, monitored feeding duration time and positioning restrictions | Other: Study Arm - acid suppression plus feeding bundle<br>* Omeprazole 0.5-1.5 milligrams/kilogram/dose twice a day (BID) Total fluid volume restriction (120-140 milliliters/kilogram/day) Feeding duration over 30 minutes Infant feeds with right side down Infant is placed on back following feeds<br>|
| Other: Conventional<br>Treated with omeprazole. This group of subjects will receive the current standard treatment for Gastro-esophageal reflux disease (GERD) which includes use of acid suppressive medication with no restrictions of the feeding volume, duration or positioning. | Other: Conventional arm - acid suppression only<br>* -Omeprazole 0.5-1.5 milligrams/kilogram/dose twice a day (BID)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CLINICAL OUTCOME OF FEEDING SUCCESS | The primary endpoint is the feeding success defined as achieving full oral feeds (defined as no need for tube feeds to maintain hydration and nutrition) and/or a >/= 6 point decrease from baseline symptom score as described by the Infant-Gastro-Esophageal Reflux Questionnaire-Revised. The minimum score is 0 (no symptoms) and the maximum score is 42 (maximum symptoms). Any total score greater than or equal to 16 is considered abnormal. | Up to 5 weeks after enrollment | 
| MOTILITY OUTCOMES: Presence of Esophageal Peristaltic Reflexes | This is part of Aim 2 of this RCT, which is a mechanistic outcome designed to understand the reasons for the clinical outcome. Presence of peristaltic reflex mechanisms elicited upon esophageal provocation during esophageal manometry were compared within the groups, week-5 vs. week-0. Odds ratios (ORs) with 95% confidence interval (CI) are reported from Generalized Estimation Equation models. | 5 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CLINICAL OUTCOMES: Growth Outcome Measure | Growth: The investigators will measure and track weight growth velocity during the study period | at 5 weeks | 
| CLINICAL OUTCOME: Development Outcome Measures | Feeding Milestones: The investigators will track feeding method at 1 year. | Up to 1 year age | 
| CLINICAL OUTCOME: Respiratory Outcome Measures | Supplemental oxygen requirement at discharge was recorded for both groups | at discharge | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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infant, esophagitis, neonate, GERD