Defining Normal Citrulline Levels as a Diagnostic Tool for Screening of Gastrointestinal Disease in Premature Infants

Terminated

• Conditions: Necrotizing Enterocolitis; Premature Newborn
• Interventions: Diagnostic Test: Citrulline samples

• Registration Number: NCT01062828
• Lead Sponsor: University of Miami

Brief Summary

Since the first description of citrulline as a potential marker for intestinal function in 1998, its use has been investigated in a variety of disease processes including Short Bowel Syndrome, Celiac disease, chemotherapy and radiation induced intestinal injury, infections producing intestinal cytopathic effects like Adenovirus, and predicting rejection in intestinal transplantation. The use of citrulline levels as a diagnostic tool to predict gastrointestinal disease in the premature population has not been properly addressed.

The introduction of enteral nutrition in the premature infant is a process of trial and error, knowing that the immaturity of the gastrointestinal system may lead to frequent episodes of feeding intolerance. This is augmented by the fear of the development of necrotizing enterocolitis (NEC) once feeds are commenced. NEC is a condition characterized by disruption of the intestinal epithelial barrier, a pathogenic process shared with some of the conditions mentioned above for which citrulline has proven clinically useful.

A normal pattern of citrulline production has not been established in the premature population. Previous studies have shown decreased levels of glutamine and arginine in premature infants up to 10 days prior to the development of necrotizing enterocolitis. Glutamine and arginine are two amino acids closely involved in the synthesis and catabolism of citrulline.

The investigators therefore hypothesize that defining a normal pattern of citrulline production in the premature population may prove to be a clinically useful diagnostic tool to screen for gastrointestinal disease.

Detailed Description

The use of citrulline levels as a diagnostic tool to predict gastrointestinal disease in the premature population has not been properly addressed.

Study Timeline

• Study Start: 2009-07
• Study First Submitted: 2010-02-03
• Study First Submitted QC: 2010-02-03
• Study First Posted: 2010-02-04
• Primary Completion: 2017-07
• Study Completion: 2017-07
• Status Verified: 2017-08
• Last Update Submitted: 2017-08-24
• Last Update Posted: 2017-08-28

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

1. Premature infants with gestational age between <32 weeks regardless of birth weight

Exclusion Criteria

1. Inborn errors of metabolism
2. Need for exchange transfusion
3. Multiple congenital anomalies
4. Renal failure (defined as urine output <1ml/k/h >24h, creatinine >1.8, or diagnosis of "non-oliguric renal failure" as determined by Pediatric nephrology)

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Gestational age < 32 weeks	Citrulline samples	Premature infants with gestational age between \<32 weeks regardless of birth weight

Primary Outcome Measures

Name	Time	Method
The primary outcome is to establish the normal pattern of citrulline concentration in the premature population, infants born <32 weeks gestation, which represents normal maturity of the intestinal glutamine pathway.	From birth to one month corrected age (Gestational age 44 weeks) or discharge from neonatal intensive care unit (NICU)	Levels of citrulline concentration in premature infants

Secondary Outcome Measures

Name	Time	Method
A secondary outcome, in the subgroup of infants who develop necrotizing enterocolitis, will be to evaluate the pattern of citrulline concentration prior to its development.	From birth until discharge from NICU	levels of citrulline concentration in prematureinfants with NEC

Trial Locations

Locations (1)

Holtz Children's Hospital- University of Miami/Jackson Memorial Hospital; 🇺🇸 Miami, Florida, United States