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

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.

Study Overview

• Status: Terminated
• Conditions: Necrotizing Enterocolitis; Premature Newborn
• Intervention / Treatment: Diagnostic test: Citrulline samples

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 Type: Observational
• Enrollment (Actual): 60

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • Holtz Children's Hospital- University of Miami/Jackson Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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.

Description

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 Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Gestational age < 32 weeks; Premature infants with gestational age between <32 weeks regardless of birth weight

Diagnostic test: Citrulline samples; Citrulline samples will be collected at the time of other lab work twice a week from enrollment until 40 weeks postconceptional age and once a week until 44 weeks postconceptional age (1 month corrected age) OR discharge from NICU(whichever is soonest). In subgroup developing NEC, citrulline samples will be collected twice a week from enrollment until discharge from NICU or death.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Levels of citrulline concentration in premature infants	From birth to one month corrected age (Gestational age 44 weeks) or discharge from neonatal intensive care unit (NICU)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	levels of citrulline concentration in prematureinfants with NEC	From birth until discharge from NICU

Collaborators and Investigators

• Sponsor: University of Miami
• Investigators: Study Director: Jennifer Garcia, MD, University of Miami, Dept of Pediatrics, Division of GI, Hepatology and Nutrition; Principal Investigator: Teresa Del Moral, MD, University of Miami, Dept of Pediatrics, Division of Neonatology; Study Chair: John Thompson, MD, The Children's Hospital at Montefiore

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (Actual): July 1, 2017
• Study Completion (Actual): July 1, 2017

Study Registration Dates

• First Submitted: February 3, 2010
• First Submitted That Met QC Criteria: February 3, 2010
• First Posted (Estimate): February 4, 2010

Study Record Updates

• Last Update Posted (Actual): August 28, 2017
• Last Update Submitted That Met QC Criteria: August 24, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: Prematurity; Necrotizing Enterocolitis; Feeding Intolerance
• Additional Relevant MeSH Terms: Gastroenteritis; Intestinal Diseases; Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Premature Birth; Enterocolitis; Enterocolitis, Necrotizing; Gastrointestinal Diseases; Digestive System Diseases
• Other Study ID Numbers: 20081180

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO