The Impact of Oligosaccharides and Bifidobacteria on the Intestinal Microflora of Premature Infants

Study Overview
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Brief Summary
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The purpose of this study is to see whether dietary supplements can change the germs in the intestines of premature infants to be more like those of healthy breast fed term babies.

Detailed Description
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To determine the optimum dose and optimum dietary supplement to promote a fecal microflora in the formula fed premature infant that is similar to that of the term breast fed infant (a predominance of bifidobacteria). In the initial phase of this trial, 30 premature infants will be randomly assigned to receive increasing doses of one of four dietary supplements: Permeate (a pasteurized human milk concentrate containing human milk oligosaccharides processed by Prolacta), GOS (galacto-oligosaccharides manufactured by Friesland foods), Bifidobacterium infantis or Bifidobacterium animalis. Weekly stool specimens will be examined by PCR to determine content of bifidobacteria and total bacteria. This study is limited to formula fed infants in order to avoid the confounding effects of the human milk oligosaccharides in breast milk. An additional 12 human milk fed infants will be enrolled and will have their diet supplemented with ProlactPlus (a pasteurized human milk concentrate containing humna milk oligosaccharides) or powdered human milk fortifier for comparison

Official Title
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Phase 1A Study of Impact of Oligosaccharides and Bifidobacteria on the Intestinal Microflora of Premature Infants

Conditions
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Fecal Microflora in the Formula Fed Premature Infant

Intervention / Treatment
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* Dietary Supplement: ProlactPlus
* Dietary Supplement: GOS galacto-oligosaccharides
* Dietary Supplement: Bifidobacterium infantis
* Dietary Supplement: Bifidobacterium animalis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Born in or transferred to UCDMC within the first two weeks of life. Birth weight less than 1500 grams. Gestational age less than 33 completed weeks. Exclusively formula fed. Exclusion Criteria: Gastrointestinal or cardiac anomalies.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Permeate | Dietary Supplement: ProlactPlus<br>* Group 1 infants will be fed a concentration of Permeate mixed with formula. The ProlactPlus will be increased each week as follows: week 1 95:5 (formula:ProlactPlus), week 2 90:10, week 3 85:15, week 4 80:20, and week 5 75:25. Caloric content is roughly as follows: week 1 21 cal/oz, week 2 22 cal/oz, week 3 23 cal/oz, week 4 24 cal/oz, and week 5 25 cal/oz.<br>* Other names: human milk oligosaccharides;|
| Active Comparator: 2<br>GOS | Dietary Supplement: GOS galacto-oligosaccharides<br>* Group 2 infants will have their formula supplemented with galacto-oligosaccharides (GOS) for each feeding as follows: week 1 0.25 g/dL, week 2 0.5 g/dL, week 3 1.0 g/dL, week 4 1.5 g/dL, and week 5 2.0 g/dL.<br>* Other names: galacto-oligosaccharides;|
| Active Comparator: 3<br>Bifidobacterium infantis | Dietary Supplement: Bifidobacterium infantis<br>* Group 3 infants will have their formula supplemented with B. infantis twice daily increasing the dose each week as follows: week 1 5x107, week 2 1.5x108, week 3 4.5x108, week 4 1.4x109, and week 5 4.2x109.<br>* Other names: B. infantis;|
| Active Comparator: 4<br>Bifidobacterium animalis | Dietary Supplement: Bifidobacterium animalis<br>* Group 4 infants will have their formula supplemented with B. animalis twice daily increasing the dose each week as follows: week 1 5x107, week 2 1.5x108, week 3 4.5x108, week 4 1.4x109, and week 5 4.2x109.<br>* Other names: bifidobacteria;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the optimum dose and optimum dietary supplement to promote a fecal microflora in the formula fed premature infant that is similar to that of the term breast fed infant (a predominance of bifidobacteria). |  | six weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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probiotic, prebiotic, oligosaccharides, GOS, galacto oligosaccharides, Bifidobacterium infantis, Bifidobacterium animalis