Intestinal Permeability in Preterm Infants

Phase 1

Completed

Conditions: Intestinal Permeability
Prematurity

Interventions: Drug: Lactulose -rhamnose solution

Registration Number: NCT01756040

Lead Sponsor: University of Maryland, Baltimore

Brief Summary: Necrotizing enterocolitis (NEC) is a life-threatening, gastrointestinal emergency characterized by increased intestinal permeability, affects approximately 7 to 10% of infants \<1500 g birthweight, and typically occurs within 7 to 14 days of birth. Mortality is as high as 30-50%. Prematurity is the greatest risk factor for the development of NEC due to the physiological immaturity of the gastrointestinal tract and altered or abnormal gut microbiota. Several studies have demonstrated that the initiation of an intense systemic and local inflammatory cascade leads to intestinal necrosis. The human intestine is lined by a single layer of cells exquisitely responsive to multiple stimuli and is populated by a complex climax community of microbial partners. Under normal circumstances, these intestinal cells form a tight but selective barrier to "friends and foes": microbes and most environmental substances are held at bay, but nutrients are absorbed efficiently. Epithelial barrier integrity is itself dynamic and matures over time starting soon after birth, though the mechanisms regulating dynamic permeability are poorly understood. Low birth weight, prematurity, and early postnatal age are associated with a leaky gut. Although intestinal permeability is higher at birth in preterm than term infants, there is usually rapid maturation of the intestinal barrier over the first few days of life in both populations. The investigators hypothesize that increased levels of measures of intestinal permeability (urine lactulose/rhamnose (LA/Rh), and fecal alpha1- antitrypsin will identify infants at high risk for NEC and that intestinal probiotic strains will be associated with intestinal barrier maturation. The purpose of the study is to determine whether clinical factors in combination with non-invasive stool test such as antitrypsin (A1AT) and microbiota composition profile are associated with intestinal permeability determined by excretion of non-metabolized sugar probes in urine (LA/Rh ratio). These studies may lead to a non-invasive screening test to identify preterm infants at risk for NEC.

Detailed Description: The proposed study will evaluate the intestinal permeability measured by the urinary La/Rh ratio at one timepoint between d7-10 of life in 200 preterm infants 24-32 weeks gestation in preparation for a future study of probiotics to improve intestinal permeability in this population.

Primary Objective: To estimate mean and variance in IP measured by urinary Lactulose/Rhamnose ratio at 7-10d of life in neonates born between 24 and 32 weeks of gestational age.

Secondary Objectives

1) To assess stool microbiome characteristics in association with intestinal permeability in preterm infants measured by the urinary lactulose/rhamnose ratio.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 211

Inclusion Criteria

<5 days
Gestational age 24-32 weeks

Exclusion criteria:

Nonviable or planned withdrawal of care
Significant GI dysfunction (e.g. heme-positive stools, abdominal distension (girth >2 cm baseline), or bilious emesis/aspirates.
Triplet or higher order multiple
Severe asphyxia
Lethal chromosome abnormalities
Cyanotic congenital heart disease
Intestinal atresia or perforation
Abdominal wall defects
Known galactosemia or other galactose intolerance

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Lactulose - rhamnose solution	Lactulose -rhamnose solution	Preterm Infants age 24-32 weeks gestation

Primary Outcome Measures

Name	Time	Method
Intestinal Permeability	7-10 days postnatal	Intestinal Permeability measured by urinary excretion of orally administered lactulose/rhamnose (La/Rh ratio)

Secondary Outcome Measures

Name	Time	Method
Breastmilk Feeding Duration Prior to La/Rh Measurement	7-10 days postnatal	Number of days breast milk feeding prior to La/Rh measurement between d7-10 days of age.
Stool Microbiota Relative Abundance	7-10 days postnatal	Relative abundance (%) Clostridiales species
Stool Alpha-1 Antitrypsin	7-10 days postnatal	Stool alpha-1 antitrypsin concentrations