Clinical trial NCT01062828: Defining Normal Citrulline Levels as a Diagnostic Tool for Screening of Gastrointestinal Disease in Premature Infants
Official title: Defining Normal Citrulline Levels as a Diagnostic Tool for Screening of Gastrointestinal Disease in Premature Infants
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Premature Newborn
Necrotizing Enterocolitis
Keywords: Prematurity
Necrotizing Enterocolitis
Feeding Intolerance
Lead sponsor: University of Miami
Sponsor class: OTHER
First posted: 2010-02-04
Enrollment: 60
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Premature infants with gestational age between \<32 weeks regardless of birth weight born at University of Miami/Holtz Children's Hospital Neonatal Intensive Care Unit, or transferred in within the first 72h of life.

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.

Eligibility criteria: 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)

Primary outcomes:
measure: 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.
timeFrame: From birth to one month corrected age (Gestational age 44 weeks) or discharge from neonatal intensive care unit (NICU)
Secondary outcomes:
measure: 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.
timeFrame: From birth until discharge from NICU
Other outcomes:
Locations:
city: Miami
country: United States
facility: Holtz Children's Hospital- University of Miami/Jackson Memorial Hospital
state: Florida
Study officials:
affiliation: University of Miami, Dept of Pediatrics, Division of GI, Hepatology and Nutrition
name: Jennifer Garcia, MD
role: STUDY_DIRECTOR
affiliation: University of Miami, Dept of Pediatrics, Division of Neonatology
name: Teresa Del Moral, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Children's Hospital at Montefiore
name: John Thompson, MD
role: STUDY_CHAIR
References: