Gastrointestinal Microbiome Influence on the Development of Bronchopulmonary Dysplasia (MiBPD)

May 8, 2023 updated by: Kent Avery Willis, MD, University of Tennessee

Gastrointestinal Microbiota Influence on the Pathogenesis of Bronchopulmonary Dysplasia in Very Low Birthweight Neonates

The purpose of this study is to advance our knowledge of the factors that contribute to the development of bronchopulmonary dysplasia (BPD), a chronic lung affecting premature infants. Specifically, the investigators will determine the complexity of the gut microbiota, the genera of the bacteria that naturally live in the gut, and determine if the relative diversity of the gut bacteria is a prognostic indicator of BPD. To accomplish this, the investigators propose to characterize the microbiota of human premature newborns with BPD, then validate this potential mechanism in mice. The investigators will enroll very low birthweight premature infants admitted to the neonatal intensive care units (NICU) at Le Bonheur Children's Hospital and Regional One Health that are at high risk to develop BPD. A cohort of well full term newborns will also be enrolled. Non-invasive stool samples will be obtained weekly over the first month of life. Infants that eventually develop BPD will be paired with infants that did not develop BPD. Stool samples from these infants will be sent for analysis. The investigators expect that reduced complexity of the gut microbiome is associated with BPD. The investigators will model the contribution of reduced microbiome complexity to the risk to develop BPD or death, as well as the association with disease severity. The project investigates important factors leading to the development of BPD, and has the potential to directly translate to therapy for the most significant pulmonary complication of prematurity.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Actual)

197

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Tennessee
      • Memphis, Tennessee, United States, 38105
        • Lebonheur Children's Hospital
      • Memphis, Tennessee, United States, 38105
        • Regional One Health

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 1 week (Child)

Accepts Healthy Volunteers

N/A

Sampling Method

Probability Sample

Study Population

Study Population will be composed of VLBW infants (birthweight less than 1500 grams) and their mothers (Including 40 term infants and their mothers)

Description

Inclusion Criteria:

  1. Newborn humans less than 1 week of age with a birthweight less than 1,500 g, or fetuses with impending delivery and estimated birthweight of less than 1,500 grams. No individuals will be excluded on the basis of sex or ethnicity.
  2. Parents can understand and comply with planned study procedures.
  3. Parents provide assent/permission prior to any study procedures.

Inclusion criteria mothers:

1. The mother's of infants meeting the infant inclusion criteria above.

Exclusion Criteria:

  1. Diagnosed immunodeficiency disorder.
  2. Currently receiving investigational immunomodulatory, probiotic or antiviral agent.
  3. Infants whose mothers meet the exclusion criteria below.

Exclusion criteria mothers:

  1. Diagnosed immunodeficiency disorder
  2. Currently receiving investigational immunomodulatory, probiotic or antiviral agents
  3. Lacking the mental capacity (e.g. due to pain, anesthesia, mental impairment) to provide informed consent for themselves or assent for the participation of their infant.
  4. Having an infant that meets the infant exclusion criteria.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Exploration Cohort
Up to 150 VLBW (very low birthweight) infants enrolled from the Regional One Health NICU (neonatal intensive care unit). Weekly stool samples will be obtained. After 36 weeks infants diagnosed with BPD per NIH guidelines, will be matched with infants without BPD. Stool samples from these infants will be sent for 16s rRNA (ribosomal ribonucleic acid) sequencing after conclusion of initial enrollment period. ITS (internal transcribed spacer) DNA may also be used to characterize fungal communities.
Diagnostic test: 16S rRNA stool microbiome sequencing.
This is an observational cohort that will undergo gut microbiome sequencing.
Validation Cohort
Up to 10 VLBW infants enrolled from the Le Bonheur Children's Hospital NICU. Weekly stool samples will be obtained. After 36 weeks infants diagnosed with BPD per NIH guidelines willl be matched with infants without BPD. Stool samples from these infants will be sent for 16s rRNA sequencing after conclusion of initial enrollment period.
Diagnostic test: 16S rRNA stool microbiome sequencing.
This is an observational cohort that will undergo gut microbiome sequencing.
Well Baby Cohort
40 Well Baby Infants have been enrolled and may be used for secondary analysis of microbial community composition of the meconium.
Diagnostic test: 16S rRNA stool microbiome sequencing.
This is an observational cohort that will undergo gut microbiome sequencing.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Bronchopulmonary dysplasia (BPD)
Time Frame: 36 weeks corrected gestational age, until the date of death or initial hospital discharge whichever occurs first, assessed up to up to 3 months
National Institute of Child Health and Disease (NICHD) consensus definition
36 weeks corrected gestational age, until the date of death or initial hospital discharge whichever occurs first, assessed up to up to 3 months
Death
Time Frame: from the date of enrollment until the date of death or initial hospital discharge, whichever occurs first, assessed up to up to 3 months
from the date of enrollment until the date of death or initial hospital discharge, whichever occurs first, assessed up to up to 3 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Necrotizing Enterocolitis (NEC)
Time Frame: from the date of enrollment until the date of initial hospital discharge or death, whichever occurs first, assessed up to up to 3 months
Modified Bell's staging for NEC > Stage 2
from the date of enrollment until the date of initial hospital discharge or death, whichever occurs first, assessed up to up to 3 months
Maternal Chorioamnionitis
Time Frame: presence on admission
presence on admission

Other Outcome Measures

Outcome Measure
Time Frame
Maternal perinatal antibiotic exposure
Time Frame: from hospital admission until birth of infant
from hospital admission until birth of infant
Infant antibiotic exposure
Time Frame: birth until 36 weeks corrected gestational age
birth until 36 weeks corrected gestational age

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Tennessee

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 5, 2017

Primary Completion (Actual)

December 30, 2020

Study Completion (Actual)

December 30, 2020

Study Registration Dates

First Submitted

July 11, 2017

First Submitted That Met QC Criteria

July 24, 2017

First Posted (Actual)

July 26, 2017

Study Record Updates

Last Update Posted (Actual)

May 10, 2023

Last Update Submitted That Met QC Criteria

May 8, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 17-05311-XP

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

MiSeq data will be placed in a public repository

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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