Neutrophil Extracellular Trap Formation in Newborn Infants at Risk for Necrotizing Enterocolitis

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2013 by University of Utah
Sponsor:
Information provided by:
University of Utah
ClinicalTrials.gov Identifier:
NCT01106209
First received: April 15, 2010
Last updated: September 10, 2013
Last verified: September 2013
  Purpose

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.


Condition
Prematurity
Necrotizing Enterocolitis

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Neutrophil Extracellular Trap Formation in Newborn Infants at Risk for Necrotizing Enterocolitis

Resource links provided by NLM:


Further study details as provided by University of Utah:

Primary Outcome Measures:
  • Time to Maturation of Neutrophil Extracellular Trap(NET) Formation [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    The objective is to characterize the time to maturation of NET formation capability in polymorphonuclear leukocytes(PMNs)isolated from newborn infants.


Secondary Outcome Measures:
  • Determine Whether NETs Contribute to the Pathogenesis of Necrotizing Enterocolitis(NEC) [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    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.


Biospecimen Retention:   Samples With DNA

blood and intestinal tissue samples


Estimated Enrollment: 60
Study Start Date: April 2010
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts
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

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.

  Eligibility

Ages Eligible for Study:   up to 1 Year
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.

Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01106209

Contacts
Contact: Christian C Yost, MD 801/581-7052 christian.yost@hsc.utah.edu

Locations
United States, Utah
University of Utah Recruiting
Salt Lake City, Utah, United States, 84108
Contact: Christian C Yost, MD    801-581-7052    christian.yost@hsc.utah.edu   
Principal Investigator: Christian C Yost, MD         
Sub-Investigator: Andrew S. Weyrich, Ph.D.         
Sub-Investigator: Guy A Zimmerman, MD         
Primary Children's Medical Center Recruiting
Salt Lake City, Utah, United States, 84112
Contact: Christian C Yost, MD    801-581-7052    christian.yost@hsc.utah.edu   
Principal Investigator: Christian C Yost, MD         
Sub-Investigator: Michael D. Rollins, MD         
Sub-Investigator: Amy Lowichik, MD         
Sponsors and Collaborators
University of Utah
Investigators
Principal Investigator: Christian C Yost, MD University of Utah
  More Information

No publications provided

Responsible Party: Christian Con Yost, University of Utah
ClinicalTrials.gov Identifier: NCT01106209     History of Changes
Other Study ID Numbers: 39621
Study First Received: April 15, 2010
Last Updated: September 10, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Utah:
premature infants
polymorphonuclear leukocytes
PMNs
neutrophil extracellular traps
NET formation
necrotizing enterocolitis

Additional relevant MeSH terms:
Enterocolitis
Enterocolitis, Necrotizing
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases

ClinicalTrials.gov processed this record on July 24, 2014