Clinical trial NCT00828451: Collaborative Research Group for Necrotizing Enterocolitis
Official title: Collaborative Research Group for Necrotizing Enterocolitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Prematurity
Necrotizing Enterocolitis
Keywords: newborn
necrotizing enterocolitis
genetics
growth factors
metabolism
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2009-01-26
Enrollment: 29
Sex: ALL
Minimum age (years): 1
Maximum age (years): 7
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: This proposal will test the hypothesis that synthesis and catabolism of epidermal growth factor (EGF), the genotype of the EGF gene, and the microbiome interact to influence EGF expression in infants at risk for necrotizing enterocolitis (NEC).

Detailed description: * Preterm infants will receive a six hour intravenous infusion of \[5,5,5-2H3\]leucine (2H3) through an existing intravenous line (IV) to measure EGF synthesis rate.
* Two blood samples will be obtained, one prior to the start of infusion, and one during the infusion. The enrichment of the stable isotope labeled leucine will be measured in the plasma from these samples; DNA will be extracted from the residual cell pellets. The EGF and EGF receptor genes will be sequenced.
* Saliva and urine will be obtained for 5 days following infusion to measure EGF and the rate of incorporation of leucine into EGF using liquid chromatography (LC)/mass spectroscopy (MS)/MS technology, as well as enzyme-linked immunosorbent assay (ELISA) . Saliva will be obtained by a Q tip swab and urine and stool obtained from the diaper.
* Stool will be obtained every 3 to 7 days through 5 weeks to evaluate inflammatory markers and the microbiome.
* If breastfeeding, a single sample of mother's milk will be obtained for measurement of EGF after adequate volumes for infant feeds are achieved.

Eligibility criteria: Inclusion Criteria:

* gestation 32 weeks or less
* 1 week of age or less
* intravenous line in place for clinical purposes

Exclusion Criteria:

* imminent death
* active infection
* pre-existing diagnosis of NEC
* fluid or electrolyte imbalance

Primary outcomes:
measure: Salivary EGF (Epidermal Growth Factor) Protein Levels
timeFrame: Sampling occurred on average day of life 9 with a range from day of life 7 to 21
measure: Urinary EGF Protein Levels
timeFrame: Sampling occurred on average day of life 9 with a range from day of life 7 to 21
Secondary outcomes:
measure: EGF Gene Sequencing
timeFrame: Sampling occurred on average day of life 9 with a range from day of life 7 to 21
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: St. Louis Children's Hospital
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Aaron Hamvas, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Nair RR, Warner BB, Warner BW. Role of epidermal growth factor and other growth factors in the prevention of necrotizing enterocolitis. Semin Perinatol. 2008 Apr;32(2):107-13. doi: 10.1053/j.semperi.2008.01.007.
citation: Warner BB, Ryan AL, Seeger K, Leonard AC, Erwin CR, Warner BW. Ontogeny of salivary epidermal growth factor and necrotizing enterocolitis. J Pediatr. 2007 Apr;150(4):358-63. doi: 10.1016/j.jpeds.2006.11.059.
citation: Spence KL, Zozobrado JC, Patterson BW, Hamvas A. Substrate utilization and kinetics of surfactant metabolism in evolving bronchopulmonary dysplasia. J Pediatr. 2005 Oct;147(4):480-5. doi: 10.1016/j.jpeds.2005.04.039.
citation: Bohlin K, Patterson BW, Spence KL, Merchak A, Zozobrado JC, Zimmermann LJ, Carnielli VP, Hamvas A. Metabolic kinetics of pulmonary surfactant in newborn infants using endogenous stable isotope techniques. J Lipid Res. 2005 Jun;46(6):1257-65. doi: 10.1194/jlr.M400481-JLR200. Epub 2005 Mar 16.