IPPI: Intestinal Permeability in Preterm Infants

Sponsor

University of Maryland, Baltimore (Other)

Overall Status

Completed

CT.gov ID

NCT01756040

Collaborator

(none)

214

Enrollment

Location

Arm

102.9

Actual Duration (Months)

2.1

Patients Per Site Per Month

Study Details

Study Description

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 (serum zonulin, urine lactulose/rhamnose (LA/Rh), and fecal alpha1- antitrypsin will identify infants at high risk for NEC. The purpose of the study is to determine whether measurement of intestinal permeability in serum will correlate with other markers of intestinal barrier leakiness measured in urine (LA/Rh) and stool (alpha-1 antitrypsin. If there is good correlation, then zonulin or serum rhamnose may be a useful measure to identify preterm babies at risk for NEC.

Condition or Disease	Intervention/Treatment	Phase
Prematurity Intestinal Permeability	Drug: Lactulose -rhamnose solution	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

214 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Screening

Official Title:

Gut Permeability in Very Low Birth Weight Infants

Actual Study Start Date :

Feb 1, 2013

Actual Primary Completion Date :

Aug 31, 2021

Actual Study Completion Date :

Aug 31, 2021

Arms and Interventions

Arm	Intervention/Treatment
Other: Lactulose - rhamnose solution Preterm Infants age 24-32 weeks gestation	Drug: Lactulose -rhamnose solution Measurement of intestinal permeability by use of mon- digestible sugars known not to cross the intestinal barrier in normal healthy intestinal tissue Other Names: dual sugar solution

Arm

Intervention/Treatment

Other: Lactulose - rhamnose solution

Preterm Infants age 24-32 weeks gestation

Drug: Lactulose -rhamnose solution

Measurement of intestinal permeability by use of mon- digestible sugars known not to cross the intestinal barrier in normal healthy intestinal tissue

Other Names:

dual sugar solution

Outcome Measures

Primary Outcome Measures

Intestinal permeability [7 years]
Intestinal Permeability measured by urinary excretion of orally administered lactulose/rhamnose (La/Rh ratio)

Secondary Outcome Measures

Stool alpha-1 antitrypsin [7 years]
Stool alpha-1 antitrypsin concentrations
Stool microbiota relative abundance [7 years]
Relative abundance (%) Clostridiales species
Clostridiales absolute copy number [7 years]
absolute copy number of Clostridiales species/g stool

Other Outcome Measures

Occurrence of Necrotizing enterocolitis [7 years]
Frequency of ≥ Stage 2 Necrotizing enterocolitis
Duration of antibiotic exposure [7 years]
Number of days of antibiotic exposure
Breastmilk feeding initiation [7 years]
Postnatal age when breast milk feeding initiated
Postnatal age full feeds reached [7 years]
Postnatal age when all nutrition is provided by enteral feeds

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 4 Days

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Maryland Medical Center	Baltimore	Maryland	United States	21201

Sponsors and Collaborators

University of Maryland, Baltimore

Investigators

Principal Investigator: Alessio Fasano, MD, Massachusetts General Hospital
Principal Investigator: Rose M Viscardi, MD, University of Maryland, College Park