Effect of Acid Suppression Medication on Pediatric Microbiome

Effect of Proton Pump Inhibitors on the Colonic Microbiome in Children

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.

Study Overview

• Status: Terminated
• Conditions: Clostridium Difficile Infection
• Intervention / Treatment: Drug: Omeprazole (suspension); Other: Lifestyle Modification

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Daniel E Freedberg, MD, MS; Phone Number: 212-342-0238; Email: def2004@cumc.columbia.edu

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Morgan Stanley Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 4 years (Child)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Columbia University
• Investigators: Principal Investigator: Daniel E Freedberg, MD, MS, Columbia University; Principal Investigator: Julian S Abrams, MD, MS, Columbia University

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (Actual): January 1, 2017
• Study Completion (Actual): January 1, 2017

Study Registration Dates

• First Submitted: December 16, 2013
• First Submitted That Met QC Criteria: December 19, 2013
• First Posted (Estimated): December 20, 2013

Study Record Updates

• Last Update Posted (Actual): December 26, 2023
• Last Update Submitted That Met QC Criteria: December 5, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Gastroesophageal Reflux Disease; Clostridium Difficile Infection; Proton Pump Inhibitors; Histamine-2 Receptor Antagonists
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Clostridium Infections; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Omeprazole
• Other Study ID Numbers: AAAM9955