L-arginine Concentrations and CPS Polymorphisms in VLBW Infants

Infant, Very Low Birth Weight Clinical Trial

Official title:

Carbamoyl-phosphate Synthase Gene Polymorphisms Influencing Plasma L-arginine Concentrations in Preterm Infants

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00554866
• Other study ID #: 07-2-018
• Status: Completed
• Phase: N/A
• First received: November 6, 2007
• Last updated: October 27, 2015
• Start date: July 2007
• Est. completion date: December 2014

Study information

• Verified date: October 2015
• Source: Maastricht University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

Plasma L-arginine concentrations are decreased in premature infants with necrotizing enterocolitis (NEC). A carbamoyl-phosphate synthetase 1 (CPS1) polymorphism has been correlated with low plasma concentrations of L-arginine in neonates (> 35 weeks of gestation). Recently Moonen et al (Pediatr Res 2007; 62(2):188-90) described a correlation between this CPS1 T1405N single nucleotide polymorphism (SNP) and the presence of NEC in VLBW infants. However there is no data about the correlation between the plasma arginine concentrations and the T1405N SNP in the CPS-1 gene in VLBW infants. In the present project we postulate that T1405N SNP in the CPS-1 gene is associated with lower plasma arginine concentrations and is also a risk factor for the development of NEC.

Description:

Plasma L-arginine concentrations are decreased in premature infants with necrotizing enterocolitis (NEC). A C-to-A nucleotide transversion (T1405N) in the gene that encodes carbamoyl-phosphate synthetase 1 (CPS1), the rate-limiting enzyme in the urea cycle, has been correlated with low plasma concentrations of L-arginine in neonates (> 35 weeks of gestation). Recently Moonen et al (Pediatr Res 2007; 62(2):188-90) described a correlation between this CPS1 T1405N single nucleotide polymorphism (SNP) and the presence of NEC in VLBW infants. However there is no data about the correlation between the plasma arginine concentrations and the T1405N SNP in the CPS-1 gene in VLBW infants. In the present project we postulate that T1405N SNP in the CPS-1 gene is associated with lower plasma arginine concentrations and is also a risk factor for the development of NEC.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 477
• Est. completion date: December 2014
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 12 Hours

Eligibility

Inclusion Criteria:

• VLBW infants (< 30 weeks and < 1500 gram birth weight).

Exclusion Criteria:

• Blood transfusion, enteral or parenteral protein intake, or inhaled nitric oxide administration before time of the blood sample (obtained between 6 and 12 hours after birth).

• Parents not able to give informed consent.

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Birth Weight
• Infant, Very Low Birth Weight

Intervention

Other:
• blood sample and buccal swab sample
one blood sample (500 mL) will be obtained from each VLBW infant between 6 and12 hours after birth from an umbilical-artery or peripheral artery catheter. Additional DNA collection buccal cell samples were obtained with a sterile OmniSwab.

Locations

Country	Name	City	State
Italy	Carlo Poma Hospital	Mantova
Italy	Cattedra di Neonatologia-Università degli Studi di Milano	Milano
Netherlands	Maastricht University Hospital	Maastricht	Limburg
Spain	Complejo Universitario Hospitalario Insular-Materno Infantil	Las Palmas de Gran Canaria

Sponsors (1)

Lead Sponsor	Collaborator
Maastricht University Medical Center

Countries where clinical trial is conducted

Italy,  Netherlands,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	the association between the T1405N SNP in the CPS-1 gene and lower plasma L-arginine concentrations		2 years	No
Secondary	To determine whether the T1405N SNP in the CPS-1 gene is associated with a higher risk of NEC		4 years	No