How Reflux Medications Affect the Microbiome of Infants

• ClinicalTrials.gov Identifier: NCT03747991
• Recruitment Status: Completed
• First Posted: November 20, 2018
• Last Update Posted: August 21, 2019
• Sponsor: Nemours Children's Clinic
• Information provided by (Responsible Party): Nemours Children's Clinic

Study Description

Brief Summary:

The changes in the organisms making up the gut microbiota in infants who are taking anti-acid reflux medications (histamine 2 receptor antagonists) as compared to infants who are not taking these medications is not well-studied or understood. Whether these medications change the gut microbiota and microbiome, and what that change may imply for children on these medications, is the focus of this study.

Condition or disease
GERD; Dysbiosis

Detailed Description:

Gut microbiota dysbiosis is associated with diseases ranging from localized gastrointestinal disorders to neurologic, respiratory, metabolic, hepatic, and cardiovascular illnesses. The microbial colonization of the infant gut is known to play a key role in immunologic and metabolic pathways impacting on human health. Disruptions during the complex process of microbial colonization have been shown to increase disease susceptibility during life. A variety of factors are known to influence the gut microbiota, including mode of delivery of neonate, host genetic factors, hose immune response, diet, xenobiotics and other drugs, infections, and environmental microbial exposures.

The diagnosis of gastroesophageal reflux disease in the infant population has increased during the past two decades. Acid suppression medications are used commonly in infants for gastroesophageal reflux disease and other acid-related conditions despite little evidence of their efficacy. Multiple studies have shown adverse effects in pediatric patients using either proton pump inhibitors or H2 receptor antagonists, the two classes of acid suppression medications that are most frequently used in children. Some of these adverse effects may result from alterations in the microbiome caused by these medications. Prior studies have demonstrated significant changes in microbial composition of both gastric and intestinal microbiota with proton pump inhibitor use (5), but to the investigators' knowledge, no prior studies have looked at the effect of H2 receptor antagonists on the microbiome in healthy, full term infants.

Study Design

• Study Type: Observational
• Actual Enrollment: 12 participants
• Observational Model: Case-Control
• Time Perspective: Cross-Sectional
• Official Title: Effect of Histamine-2 Receptor Antagonists on the Microbiome of Full Term Infants
• Actual Study Start Date: August 13, 2018
• Actual Primary Completion Date: April 30, 2019
• Actual Study Completion Date: July 31, 2019

Groups and Cohorts

Group/Cohort
Control Infants; Infants ages 2 months to 12 months who are not on H2RA medication.
Treated Infants; Infants ages 2 months to 12 months who are taking H2RA medication.

Outcome Measures

Primary Outcome Measures :

1. Microbiome taxa [ Time Frame: At time of sampling - once at enrollment ]
   16S Metagenomic taxonomy of gut microbiome

Eligibility Criteria

• Ages Eligible for Study: 2 Months to 12 Months (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

Infants must be healthy, male or female term infants (gestational age ≥37 weeks) who are at least 2 months old, on or off H2RA medication, who meet inclusion/exclusion criteria. Infants will be recruited from Nemours Children's Clinic and through local advertisements in the greater Wilmington / Northern Delaware area.

Criteria

Inclusion Criteria:

• Full term, at least 2 months of age
• No exposure OR at least 14 days of exposure to H2-receptor antagonist medication
• No exposure to probiotics or antibiotics

Exclusion Criteria:

• Current or recent (within the past 14 days) gastrointestinal infection (viral, bacterial, or fungal)
• Gastrointestinal mucosal disease, or have clinically significant constipation
• Any history of exposure to proton pump inhibitors
• Unvaccinated infants
• Infants with weight-for-length either below the 3rd percentile for age or above the 97th percentile for age
• Infants with rapid weight gain, defined as change in weight-for-length z-score exceeding +0.67 from birth to 4 months of age or birth to 6 months of age

Contacts and Locations

Locations

United States, Delaware

Alfred I. duPont Hospital for Children

Wilmington, Delaware, United States, 19803

Sponsors and Collaborators

Nemours Children's Clinic

Investigators

• Principal Investigator: Matthew Di Guglielmo, MD PhD; Nemours

More Information

• Responsible Party: Nemours Children's Clinic
• ClinicalTrials.gov Identifier: NCT03747991
• Other Study ID Numbers: 1231469
• First Posted: November 20, 2018
• Last Update Posted: August 21, 2019
• Last Verified: August 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: 16S metagenomic sequence data, deidentified, will be made available through either the database of Genotypes and Phenotypes (dbGap) or Sequence Read Archive (SRA).
• Supporting Materials: Analytic Code
• Time Frame: At conclusion of the study.
• Access Criteria: To be determined.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Nemours Children's Clinic:

Infant GERD; H2RA medication

Additional relevant MeSH terms:

Dysbiosis; Pathologic Processes