A Multi-strain Synbiotic Versus a Multi-strain Probiotic in Premature Infants

Study Overview
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Brief Summary
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The aims are to 1) compare two probiotic treatments (multi-strain synbiotic vs. multi-strain probiotic) on bifidobacteria fecal colonization counts at 1, 2, 3, and 4 weeks of life, 34 weeks corrected gestation age (CGA) ; 2) compare infants successfully colonized with probiotic organisms to infants not successfully colonized at 1, 2, 3, and 4 weeks of life, 34 weeks CGA on infant outcomes and on stress biomarker patterns at birth, day of life (DOL) 1, DOL 7; 3) determine long-term safety and outcomes of probiotic treatments at 6, 16, and 24 months CGA.

Detailed Description
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Feeding Intolerance and other GI issues are a major concern in a NICU hospitalized population. Successful colonization with probiotic bacteria is thought to impact the incidence of GI related issues. This study will study the impact of prebiotics on the colonization of a population of VLBW infants in the NICU setting.

Official Title
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A Randomized Controlled Trial on a Multi-strain Synbiotic vs. a Multi-strain Probiotic on Fecal Colonization in the Very Low Birth Weight Infant

Conditions
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Feeding; Difficult, Newborn, Necrotizing Enterocolitis

Intervention / Treatment
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* Dietary Supplement: Multi-strain Probiotic


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: infants with a birth weight < 1500g admission to NICU at The Nebraska Medical Center Exclusion Criteria: infants who have congenital anomalies have a diagnosis of a congenital metabolic disease are made a ward of the State or are born to a mother < 19 years of age
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Multi-strain Synbiotic<br>Multi-strain probiotic with prebiotics | Dietary Supplement: Multi-strain Probiotic<br>* Multi-strain Synbiotic: 1.5 billion CFU of Lactobacillus acidophilus, Bifidobacterium bifidum,and Bifidobacterium lactis WITH galacto-oligosaccharide(GOS)/fructo-oligosaccharide (FOS) combination at 1g/dL (0.9g/dL GOS/ 0.1g/dL FOS)<br>* Other names: Lactobacillus;|
| Active Comparator: Multi-strain Probiotic<br>Multi-strain Probiotic without prebiotics. | Dietary Supplement: Multi-strain Probiotic<br>* Multi-strain Synbiotic: 1.5 billion CFU of Lactobacillus acidophilus, Bifidobacterium bifidum,and Bifidobacterium lactis WITH galacto-oligosaccharide(GOS)/fructo-oligosaccharide (FOS) combination at 1g/dL (0.9g/dL GOS/ 0.1g/dL FOS)<br>* Other names: Lactobacillus;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparing a multi-strain synbiotic vs. a multi-strain probiotic on mean bifidobacteria fecal colonization counts | Infants will be given the synbiotic or probiotic supplementation within the first week of life (upon inititation of enteral feedings) until approximately 34 weeks corrected gestational age. | 1,2, 3, 4 and 34 weeks of age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare the difference between two groups (multi-strain synbiotic vs. multi-strain probiotic) on demographic data and selected standard clinical infant outcomes. | Two probiotic groups will be compared on demographics: mean [birth wt(g), birth length(cm), birth hc(cm), GA at birth, 1-& 5- minute APGAR scores], race, gender, prenatal antibiotics(y/n), and enteral feeding type(breastmilk, formula, both); and on selected infant outcomes: Feeding Intolernce(number of times the feeding care plan is disrupted), NEC(y/n), late-onset sepsis(y/n), IVH(y/n;Grade I-IV), PDA(y/n), CLD(y/n), mean [endotracheal ventilation(days), inspired oxygen, discharge wt(g),discharge length(cm), discharge hc(cm), days to reach full feedings, length of stay, days on antibiotics]. | From birth to NICU discharge (average 36 weeks corrected gestational age) | 
| Compare the difference between infants successfully colonized with probiotic organisms (>10^2 colonies on a 10^4-fold dilution plate)to infants not successfully colonized on demographics and selected standard clinical outcomes | Two colonization groups will be compared on demographics: mean[birth wt(g), birth length(cm),birth hc(cm),GA at birth,1-& 5- minute APGAR scores],race, gender,prenatal antibiotics(y/n),and enteral feeding type(breastmilk, formula, both); and on selected infant outcomes: Feeding Intolernce(number of times the feeding care plan is disrupted), NEC(y/n), late-onset sepsis(y/n), IVH(y/n;Grade I-IV), PDA(y/n), CLD(y/n), mean [endotracheal ventilation(days), inspired oxygen, discharge wt(g),discharge length(cm), discharge hc(cm), days to reach full feedings, length of stay, days on antibiotics]. | 1 week of life to NICU discharge | 
| Compare infants successfully colonized with probiotic organisms(>10^2 colonies on a 10^4-fold dilution plate) to infants not successfully colonized on stress biomarker levels | Interquartile ranges of biomarkers will be compared between the two colonization groups. Biomarkers include: serum cortisol(cord blood), salivary cortisol (DOL 1,7), serum 8-hydroxydeoxyguanosine (cord blood), urinary 8-hydroxydeoxyguanosine (DOL 1,7) | day of life 1 to day of life 7 | 
| Compare trends of stress biomarker levels in relation to demographics and selected standard infant outcomes | Interquartile ranges of biomarkers (listed above) will be compared on the demographic data and selected standard infant outcomes (listed above) at each time (DOL 1, 7) and over-time. | day of life 1 to day of life 7 | 
| Compare the difference between the two probiotic treatment groups (multi-strain synbiotic vs. multi-strain probiotic) on longitudinal neurodevelopmental outcomes. | Appropriate Bayley scales conducted by developmental pediatricians will be used for the neurodevelopmental data. | 6, 16 & 24 months corrected gestational age. |