Effect of Acid Suppression Medication on Pediatric Microbiome

Study Overview
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Brief Summary
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The colonic microbiome is essential in health and disease, and is highly dynamic during the first several years of life. Proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) are widely used in children, but the effects of PPIs and H2RAs on the pediatric colonic microbiome are unknown. This study will determine whether acid suppression with these medications affects the microbiome of otherwise healthy children who are prescribed acid suppression for gastroesophageal reflux disease (GERD), and determine the duration and magnitude of microbiome changes.

Detailed Description
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Otherwise healthy children age 0-4 years old who are being considered for acid suppressive therapy for GERD will be eligible for this study. Subjects donate samples before and after being treated with PPIs or H2RAs (must donate at least 2 baseline pre-PPI samples to be eligible for final analysis). 30 total children who complete the study (anticipated 10 who receive lifestyle modification and 20 who receive PPIs or H2RAs). All children will donate 6 stools on or about weeks 0, 4, 12, 20, 38, and 64. The primary outcome will be a significant change in the overall diversity of the colonic microbiome after 8 weeks of PPIs or H2RAs (i.e., from week 12 to week 4), compared to after 4 weeks of lifestyle management.

Official Title
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Effect of Proton Pump Inhibitors on the Colonic Microbiome in Children

Conditions
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Clostridium Difficile Infection

Intervention / Treatment
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* Drug: Omeprazole (suspension)
* Other: Lifestyle Modification


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Zero to 4 years old Being considered for PPI or H2RA treatment for refractory GERD Parent is able to give informed consent Exclusion Criteria: Prevalent C. difficile infection (excluded via stool PCR at week 0) Use of systemic antibiotics within the past 90 days Use of acid suppression medications within the past 90 days (antacids allowed if none within the last 7 days) Increased risk for fracture due to vitamin D deficiency or other causes Chronic gastrointestinal disease (e.g. inflammatory bowel disease, celiac disease, microscopic colitis, malabsorptive conditions, short gut syndrome) Congenital deficiency in immunity (e.g., such as IgA deficiency) Cystic fibrosis Significant dynamic or uncontrolled comorbidity such as HIV or malignancy Use of medications with potential interaction with PPIs

Ages Eligible for Study
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Minimum Age: 0 Years
Maximum Age: 4 Years

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: Basic Science
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Omeprazole (suspension)<br>Open-label, with all subjects receiving omeprazole | Drug: Omeprazole (suspension)<br>* 1 mg/kg/day<br>* Other names: As above;|
| Other: Lifestyle Modification<br>Treated with lifestyle modification (upright feeding, smaller meals, elevation of the head of the bed, etc.) | Other: Lifestyle Modification<br>* Standard lifestyle modification: small meals, upright feeding, elevation of the head of the bed<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Fecal Microbiome Diversity, Assessed by Bray-Curtis Index Comparing Those Who Received Acid Suppression Medications to Those Who Received Lifestyle Modifications |  | From week 12 to week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Subjects Eating High Fiber Diet | At each study visit, we will assess the effects of longterm diet on the microbiome by using the Harvard-Willett Food Frequency Questionnaire. Using this data, we will classify each subject as low vs high fiber. | Up to Week 64 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Clostridium Difficile Infection, Proton Pump Inhibitors, Histamine-2 Receptor Antagonists, Gastroesophageal Reflux Disease