Intestinal Permeability in Preterm Infants (IPPI)

November 15, 2023 updated by: Rose Viscardi, University of Maryland, Baltimore

Gut Permeability in Very Low Birth Weight Infants

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

211

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • University of Maryland Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 4 days (Child)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Screening
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Intestinal Permeability
Time Frame: 7-10 days postnatal
Intestinal Permeability measured by urinary excretion of orally administered lactulose/rhamnose (La/Rh ratio)
7-10 days postnatal

Secondary Outcome Measures

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

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Occurrence of Necrotizing Enterocolitis
Time Frame: 0-28 days postnatal
Frequency of ≥ Stage 2 Necrotizing enterocolitis
0-28 days postnatal
Percent Participants Exposed to Antibiotics Prior to La/Rh Measurement
Time Frame: 7-10 days postnatal
Percent of participants with antibiotic exposure prior to La/Rh measurement
7-10 days postnatal
Postnatal Age Full Feeds Reached
Time Frame: 0-100 days postnatal
Postnatal age when all nutrition is provided by enteral feeds
0-100 days postnatal

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Maryland, Baltimore

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 1, 2013

Primary Completion (Actual)

August 31, 2021

Study Completion (Actual)

August 31, 2021

Study Registration Dates

First Submitted

December 19, 2012

First Submitted That Met QC Criteria

December 21, 2012

First Posted (Estimated)

December 24, 2012

Study Record Updates

Last Update Posted (Estimated)

November 17, 2023

Last Update Submitted That Met QC Criteria

November 15, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HP-00049647

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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