Clinical trial NCT02016820: Effect of Acid Suppression Medication on Pediatric Microbiome
Official title: Effect of Proton Pump Inhibitors on the Colonic Microbiome in Children
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Clostridium Difficile Infection
Keywords: Clostridium Difficile Infection
Proton Pump Inhibitors
Histamine-2 Receptor Antagonists
Gastroesophageal Reflux Disease
Lead sponsor: Columbia University
Sponsor class: OTHER
First posted: 2013-12-20
Enrollment: 7
Sex: ALL
Minimum age (years): 0
Maximum age (years): 4
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Fecal Microbiome Diversity, Assessed by Bray-Curtis Index Comparing Those Who Received Acid Suppression Medications to Those Who Received Lifestyle Modifications
timeFrame: From week 12 to week 4
Secondary outcomes:
measure: Percent Subjects Eating High Fiber Diet
timeFrame: Up to Week 64
Other outcomes:
Locations:
city: New York
country: United States
facility: Morgan Stanley Children's Hospital
state: New York
Study officials:
affiliation: Columbia University
name: Julian S Abrams, MD, MS
role: PRINCIPAL_INVESTIGATOR
affiliation: Columbia University
name: Daniel E Freedberg, MD, MS
role: PRINCIPAL_INVESTIGATOR
References: