Esophageal Atresia: a Natural Experiment of the Effects of Oral Inoculation on the Gut Microbiome

The purpose of this study is to understand changes of the gut microbiome due to esophageal atresia. The intervention will be to give a patient his or her own saliva through their gastrostomy tube (directly into the stomach) to observe if this can normalize microbial colonization of the gut.

Study Overview

• Status: Completed
• Conditions: Esophageal Atresia
• Intervention / Treatment: Other: Patient's own saliva

Detailed Description

After being informed about the study and its overall risks, parents will be given the option to enroll their infant. Participants (infants) with esophageal atresia and a gastrostomy tube will be given their own saliva through their gastrostomy tube, directly into the stomach. Samples of saliva and stool will be collected from these infants, and from a comparison group without esophageal atresia, as well as blood and urine to look for changes in immune responses and in metabolism.

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94304
      • Lucile Packard Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 3 months (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Neonates with Esophageal Atresia (All, no exclusion criteria); maximum age at enrollment is 3 months.
• Neonates matched for gestational age without EA, also anticipated to require surgery (Infants >=32 weeks), or also premature (<32 weeks)

Exclusion Criteria (only for infants without EA):

• sepsis
• admission to study hospital after 7 days old
• expected length of stay <2 weeks

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Infants with Esophageal Atresia; Starting at 3 weeks, infants will be administered 1 mL of their own saliva via gastrostomy tube, with each feed (8x/day) for one week.	Other: Patient's own saliva; Infants with esophageal atresia will be given their own saliva
No Intervention: Comparison Infants without Esophageal Atresia; Infants do not have EA and thus can swallow their own saliva.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Gut Microbial Community Structure	Evaluate community structure and differential abundances of dominant taxa and of key taxa to the newborn (e.g., Bifidobacterium, Bacteroides, Lactobacillus, Staphylococcus and Enterobacteriaceae)	From birth until discharge from the hospital, up to 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Immune System Profile	Determine immune cell profiles using mass cytometry (CyTOF)	From birth until discharge from the hospital, up to 1 year
Change in Fecal Metabolome Profile	Measure metabolites in the stool using mass spectrometry	From birth until discharge from the hospital, up to 1 year
Change in Blood Metabolome Profile	Measure metabolites in the blood using mass spectrometry	From birth until discharge from the hospital, up to 1 year

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: Thrasher Research Fund
• Investigators: Principal Investigator: David Relman, MD, Stanford University; Principal Investigator: Pearl Houghteling, Stanford University

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2021
• Primary Completion (Actual): April 8, 2022
• Study Completion (Actual): April 8, 2022

Study Registration Dates

• First Submitted: April 21, 2021
• First Submitted That Met QC Criteria: May 20, 2021
• First Posted (Actual): May 25, 2021

Study Record Updates

• Last Update Posted (Actual): April 13, 2023
• Last Update Submitted That Met QC Criteria: April 11, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Congenital Abnormalities; Gastrointestinal Diseases; Esophageal Diseases; Digestive System Abnormalities; Esophageal Atresia
• Other Study ID Numbers: 58102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No