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Intestinal Permeability in Preterm Infants (IPPI)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT01756040
Recruitment Status : Recruiting
First Posted : December 24, 2012
Last Update Posted : November 4, 2020
Information provided by (Responsible Party):
Rose Viscardi, 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 (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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 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 : February 1, 2013
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : June 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Birth Weight
Drug Information available for: Lactulose

Arm Intervention/treatment
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 Name: dual sugar solution

Primary Outcome Measures :
  1. Intestinal permeability [ Time Frame: 7 years ]
    Intestinal Permeability measured by urinary excretion of orally administered lactulose/rhamnose (La/Rh ratio)

Secondary Outcome Measures :
  1. Stool alpha-1 antitrypsin [ Time Frame: 7 years ]
    Stool alpha-1 antitrypsin concentrations

  2. Stool microbiota relative abundance [ Time Frame: 7 years ]
    Relative abundance (%) Clostridiales species

  3. Clostridiales absolute copy number [ Time Frame: 7 years ]
    absolute copy number of Clostridiales species/g stool

Other Outcome Measures:
  1. Occurrence of Necrotizing enterocolitis [ Time Frame: 7 years ]
    Frequency of ≥ Stage 2 Necrotizing enterocolitis

  2. Duration of antibiotic exposure [ Time Frame: 7 years ]
    Number of days of antibiotic exposure

  3. Breastmilk feeding initiation [ Time Frame: 7 years ]
    Postnatal age when breast milk feeding initiated

  4. Postnatal age full feeds reached [ Time Frame: 7 years ]
    Postnatal age when all nutrition is provided by enteral feeds

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 4 Days   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01756040

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Contact: Rose M Viscardi, MD 410-706-1913

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United States, Maryland
University of Maryland Medical Center Recruiting
Baltimore, Maryland, United States, 21201
Principal Investigator: Rose M Viscardi, MD         
Sponsors and Collaborators
University of Maryland, Baltimore
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Principal Investigator: Alessio Fasano, MD Massachusetts General Hospital
Principal Investigator: Rose M Viscardi, MD University of Maryland, College Park

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Rose Viscardi, University of Maryland, University of Maryland, Baltimore Identifier: NCT01756040    
Other Study ID Numbers: HP-00049647
First Posted: December 24, 2012    Key Record Dates
Last Update Posted: November 4, 2020
Last Verified: November 2020
Keywords provided by Rose Viscardi, University of Maryland, Baltimore:
intestinal permeability
preterm infants
dual sugar test
Additional relevant MeSH terms:
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Premature Birth
Obstetric Labor, Premature
Obstetric Labor Complications
Pregnancy Complications
Pharmaceutical Solutions
Gastrointestinal Agents