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

NCT ID: NCT00810160

Last Updated: 2017-07-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 59 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-06-30
• Study Completion Date: 2015-11-30

Brief Summary

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

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

Conditions

Fecal Microflora in the Formula Fed Premature Infant

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

1

Permeate

Group Type: ACTIVE_COMPARATOR

ProlactPlus

Intervention Type: DIETARY_SUPPLEMENT

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.

2

GOS

Group Type: ACTIVE_COMPARATOR

GOS galacto-oligosaccharides

Intervention Type: DIETARY_SUPPLEMENT

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.

3

Bifidobacterium infantis

Group Type: ACTIVE_COMPARATOR

Bifidobacterium infantis

Intervention Type: DIETARY_SUPPLEMENT

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.

4

Bifidobacterium animalis

Group Type: ACTIVE_COMPARATOR

Bifidobacterium animalis

Intervention Type: DIETARY_SUPPLEMENT

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.

Interventions

ProlactPlus

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.

Intervention Type: DIETARY_SUPPLEMENT

GOS galacto-oligosaccharides

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.

Intervention Type: DIETARY_SUPPLEMENT

Bifidobacterium infantis

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.

Intervention Type: DIETARY_SUPPLEMENT

Bifidobacterium animalis

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.

Intervention Type: DIETARY_SUPPLEMENT

Other Intervention Names

human milk oligosaccharides; galacto-oligosaccharides; bifidobacteria; B. infantis; B. animalis; bifidobacteria

Eligibility Criteria

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.

• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

University of California, Davis

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mark Underwood, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, Davis

Locations

UC Davis Medical Center

Sacramento, California, United States

Countries

United States

References

Underwood MA, Kalanetra KM, Bokulich NA, Lewis ZT, Mirmiran M, Tancredi DJ, Mills DA. A comparison of two probiotic strains of bifidobacteria in premature infants. J Pediatr. 2013 Dec;163(6):1585-1591.e9. doi: 10.1016/j.jpeds.2013.07.017. Epub 2013 Aug 29.

Reference Type: DERIVED

PMID: 23993139 (View on PubMed)

Other Identifiers

R01HD059127

Identifier Type: NIH

Identifier Source: secondary_id

View Link

HD059127-01

Identifier Type: OTHER

Identifier Source: secondary_id

243213

Identifier Type: -

Identifier Source: org_study_id