Probiotics and Early Microbial Contact in Preterm Neonates (ProPre)

Probiotic Modulation of Early Microbial Contact in Premature Infants

Probiotics are live microbes which, when administered in sufficient amounts, confer a health benefit to the host. According to recent clinical trials, administration of probiotics to very low birth weight infants significantly reduces overall mortality and risk of necrotizing enterocolitis, a devastating inflammatory intestinal disease. The investigators have previously demonstrated that administering probiotics to the lactating mother enhances the immunoprotective properties of breast milk. Despite the promising data, the optimal probiotic intervention is yet to be established. The mechanisms by which probiotics exert their effects remain largely unknown.

This research project is based on the notion that modulation of early microbial contact by probiotics may provide a safe and effective means to improve the health of preterm infants. In particular, the investigators hypothesize that the protective potential of probiotics may be enhanced via breast milk by administering probiotics to the lactating mother. All of the potentially beneficial effects of probiotic bacteria are strain-specific and therefore preliminary laboratory and clinical research with regard to different physiological targets of probiotic intervention should be carried out to guide the design of large-scale clinical trials aiming show clinical efficacy and establish clinical practice. The purpose of this research project is to identify targets for probiotic therapy in premature neonates and to provide insight into the optimal probiotic strains and administration protocol the clinical efficacy of which will subsequently be tested in a randomized controlled trial.

The specific aims of the project are:

1. To determine the effect of maternal consumption of probiotics during lactation on immunomodulatory properties of breast milk in mothers of premature infants. Concentrations of immunomodulatory factors and microbiological properties of breast milk will be measured.
2. To investigate the impact of different probiotic administration protocols on gut microbiota composition in preterm infants. In particular, the issue whether maternal probiotic consumption instead or in addition to probiotics administered to the infant is effective will be elucidated. Different potential probiotic strains will be assessed.
3. To elucidate the impact probiotic bacteria administered to the lactating mother and/or directly to the infant on gut immunophysiology in preterm infants.

Study Overview

• Status: Unknown
• Conditions: Breastfeeding; Premature; Infant, Light-for-dates
• Intervention / Treatment: Dietary supplement: LGG; Dietary supplement: Placebo; Dietary supplement: LGG+Bb-12

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Samuli Rautava, MD, PhD; Phone Number: +358 40 7033166; Email: samrau@utu.fi

Study Locations

• Finland
  • Turku, Finland, 20520
    • Recruiting
    • Turku University Hospital
    • Contact: Samuli Rautava, MD, PhD; Phone Number: +358 40 7033166; Email: samrau@utu.fi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 3 days (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• premature infant born at <35 weeks gestational age

Exclusion Criteria:

• severe asphyxia
• significant anomalies

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: placebo mother - LGG infant; Placebo is administered to the lactating mother whilst the infant receives the probiotic LGG.	Dietary supplement: LGG; Lactobacillus rhamnosus GG 10E9 cfu / day
Placebo Comparator: placebo mother - placebo infant; Placebo is administered to both the lactating mother and her infant.	Dietary supplement: Placebo; Microcrystalline cellulose is used as placebo.
Active Comparator: LGG mother - placebo infant; The probiotic LGG is administered to the lactating mother whilst the infant receives placebo.	Dietary supplement: LGG; Lactobacillus rhamnosus GG 10E9 cfu / day
Active Comparator: LGG+Bb-12 mother - Placebo infant; A combination of the probiotics LGG and Bb-12 is administered to the lactating mother, the infant receives placebo.	Dietary supplement: LGG+Bb-12; A combination of the probiotics Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb-12 administered 10E9 cfu / day each.
Active Comparator: Pacebo mother - LGG+Bb-12 infant; Placebo is administered to the lactating mother, the infant receives a combination of the probiotics LGG and Bb-12	Dietary supplement: LGG+Bb-12; A combination of the probiotics Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb-12 administered 10E9 cfu / day each.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gut microbiota	Assessment of indigenous intestinal microbiota composition in premature neonates during the first month of life	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intestinal immunity	Intestinal immune gene expression profiles will be assessed from fecal samples.	1 month
Breast milk compostion	Immunological and microbiological properties of breast milk will be investigated.	1 months

Collaborators and Investigators

• Sponsor: Turku University Hospital
• Collaborators: Massachusetts General Hospital; University of Turku
• Investigators: Principal Investigator: Samuli Rautava, MD, PhD, Turku University Hospital

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Anticipated): April 1, 2019
• Study Completion (Anticipated): April 1, 2019

Study Registration Dates

• First Submitted: October 10, 2011
• First Submitted That Met QC Criteria: October 14, 2011
• First Posted (Estimate): October 19, 2011

Study Record Updates

• Last Update Posted (Actual): April 19, 2018
• Last Update Submitted That Met QC Criteria: April 18, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: Probiotics; Breastfeeding; Intestinal microbiota; Premature infant; Intestinal immunity
• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Premature Birth
• Other Study ID Numbers: ETMK 104/180/2011