Collaborative Research Group for Necrotizing Enterocolitis

Prematurity Clinical Trial

Official title:

Collaborative Research Group for Necrotizing Enterocolitis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00828451
• Other study ID #: 08-0105
• Status: Completed
• Phase: N/A
• First received: January 22, 2009
• Last updated: March 7, 2018
• Start date: May 2008
• Est. completion date: December 2010

Study information

• Verified date: March 2018
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: December 2010
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 7 Days

Eligibility

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

Related Conditions & MeSH terms

• Enterocolitis
• Enterocolitis, Necrotizing
• Necrotizing Enterocolitis
• Prematurity

Intervention

Biological:
• [5,5,5-2H3]leucine (stable isotope labeled leucine)
intravenous infusion of labeled leucine dissolved in 5% glucose water: priming dose of 18 micromoles (1.8 ml)/kg over 5 minutes, then 18 micromoles (1.8 ml)/hr for 6 hours; one infusion total

Locations

Country	Name	City	State
United States	St. Louis Children's Hospital	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Washington University School of Medicine

Country where clinical trial is conducted

United States, 

References & Publications (4)

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. Epub 2005 Mar 16. — View 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. Review. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Salivary EGF (Epidermal Growth Factor) Protein Levels	Salivary EGF protein levels obtained from oral swabs were analyzed by commercially available EGF ELISA kit (R &D systems Inc). EGF protein levels were normalized to micrograms of protein in saliva, and expressed as picogram of EGF protein per microgram of total salivary protein.	Sampling occurred on average day of life 9 with a range from day of life 7 to 21
Primary	Urinary EGF Protein Levels	Urinary EGF protein levels obtained from free flowing urine samples retrieved from subject diaper were analyzed by commercially available EGF ELISA kit (R &D systems Inc). EGF protein levels were normalized to milligrams of creatinine in urine, and expressed as nanograms of EGF protein per milligram of urinary creatinine.	Sampling occurred on average day of life 9 with a range from day of life 7 to 21
Secondary	EGF Gene Sequencing	Identification of computationally predicted functional variants in EGF gene	Sampling occurred on average day of life 9 with a range from day of life 7 to 21