Neutrophil Extracellular Trap Formation in Newborn Infants at Risk for Inflammatory Syndromes

February 1, 2020 updated by: Christian Yost, University of Utah
The purpose of this study is to characterize the time to maturation of neutrophil extracellular trap(NET) formation capability in polymorphonuclear leukocytes(PMNs) isolated from newborn premature and term infants as well as infants <1 year of age undergoing elective surgery. This study will also determine whether NETs contribute to the pathogenesis of necrotizing enterocolitis (NEC). We hypothesize that NET formation contributes to the pathogenesis of NEC by inappropriately releasing degradative proteins and tissue destructive enzymes into the inflammatory milieu of the premature infant gastrointestinal tract following bacterial translocation. We also hypothesize that the delay in NEC development in premature infants (3rd - 4th week of life) as compared to at-risk term infants (1st week of life) results from a developmental delay in PMN ability to form NETs.

Study Overview

Status

Suspended

Conditions

Detailed Description

Prematurely born infants are at risk for necrotizing enterocolitis (NEC), the most common gastrointestinal emergency encountered in the newborn intensive care unit. This disease occurs in between 5 - 10% of infants born at less than 30 weeks gestation or less than 1500 grams birth weight. In these patients, NEC routinely develops during the 3rd or 4th week of life. NEC rarely occurs in infants born closer to term; for these patients NEC usually develops during the 1st week of life. So far, no one has explained the inverse relationship between gestational age at birth and the delay in NEC development.

Recently, our laboratory described for the first time an inherent deficiency of innate immunity in newborn infants - failure of neutrophil extracellular trap formation. Neutrophil extracellular traps or NETs are complex lattices of extracellular chromatin and DNA decorated with anti-microbial proteins and degradative enzymes which trap and kill microbes. When the neutrophils of newborn infants develop the ability to form NETs and whether the maturation of NET formation correlates with development of NEC in at risk infants remains unknown.

We have therefore undertaken the following study best described as a prospective, in vitro longitudinal cellular biology study of LPS/PAF-stimulated PMNs isolated from the cord and peripheral blood of premature infants at risk for NEC and from term infants not considered at risk for NEC. We will also assay for NET formation in gastrointestinal tissue samples obtained at the time of surgery for severe NEC in enrolled prematurely born infants. These studies are the first of their kind and aim to answer these important questions.

Study Type

Observational

Enrollment (Anticipated)

60

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
    • Utah
      • Salt Lake City, Utah, United States, 84108
        • University of Utah
      • Salt Lake City, Utah, United States, 84112
        • Primary Children's Medical Center

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 year (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Preterm and healthy term infants born at the University of Utah Hospital. Infants <1 year who are undergoing elective surgery at Primary Children's Medical Center.

Description

Inclusion Criteria:

  1. Preterm infant patients delivered at UUMC and hospitalized in the NICU who are ≤ 1500 grams or <30 weeks gestational age at birth
  2. Term infants delivered at UUMC without complication, either via cesarean section or vaginal delivery
  3. Infants admitted to the PCMC same-day surgery unit in preparation for elective surgery within the first year of life.

Exclusion Criteria:

  • No other 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

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Prematurely born infants in the NICU
Preterm infant patients delivered at UUMC and hospitalized in the NICU who are ≤1500 grams or <30 weeks gestational age at birth
Healthy term infants
Term infants delivered at UUMC without complication, either via cesarean section or vaginal delivery
Infants having surgery at <1 year old
Infants admitted to the PCMC same-day surgery unit in preparation for elective surgery within the first year of life

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to Maturation of Neutrophil Extracellular Trap(NET) Formation
Time Frame: 5 years
The objective is to characterize the time to maturation of NET formation capability in polymorphonuclear leukocytes(PMNs)isolated from newborn infants.
5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determine Whether NETs Contribute to the Pathogenesis of Necrotizing Enterocolitis(NEC)
Time Frame: 5 years
The purpose is to determine if NET formation contributes to the pathogenesis of NEC by inappropriately releasing degradative proteins and tissue destructive enzymes into the inflammatory milieu of the premature infant gastrointestinal tract following bacterial translocation.
5 years

Collaborators and Investigators

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

Sponsor

University of Utah

Collaborators

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

  • Principal Investigator: Christian C Yost, MD, University of Utah

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

April 1, 2010

Primary Completion (Anticipated)

March 31, 2023

Study Completion (Anticipated)

March 31, 2023

Study Registration Dates

First Submitted

April 15, 2010

First Submitted That Met QC Criteria

April 15, 2010

First Posted (Estimate)

April 19, 2010

Study Record Updates

Last Update Posted (Actual)

February 5, 2020

Last Update Submitted That Met QC Criteria

February 1, 2020

Last Verified

February 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 119244
  • R01HD093826 (U.S. NIH Grant/Contract)

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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