Lactobacillus Reuteri DSM17938 in C-Section Infants

Influence of Lactobacillus Reuteri DSM17938 on Early Gut Microbial Colonization in Infants Born by Caesarean Section: A Double-blinded, Randomized, Placebo-controlled Study

RCT designed to evaluate the impact of Lactobacillus reuteri DSM17938 to modify gut microbiota in children delivered by C-section

Study Overview

• Status: Completed
• Conditions: C-section
• Intervention / Treatment: Dietary supplement: Lactobacillus reuteri DSM17038; Other: Placebo for Probiotics

Detailed Description

RCT designed to evaluate the safety and efficacy of L. reuteri DSM17938 administrated to newborns babies to modify the fecal microbiome after 30 days of supplementation. Secondary Secondary endpoints will be evaluate the occurrence and frequency of AEs Day 0 to Day 60; The gut bacterial composition Day 7 and Day 30 as described in primary endpoint; the gut bacterial composition in infants born by c-section and supplemented with L. reuteri DSM17938 compared to the gut bacterial composition in infants born vaginally and the salivary concentration of IgA at 48h ±3h after birth and at Day 30.

• Study Type: Interventional
• Enrollment (Actual): 69
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Mexico
  • Tlalpan
    • Mexico city, Tlalpan, Mexico, 14080
      • Hospital General Dr. Manuel Gea Gonzalez

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 hours to 1 day (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Gestational age >37weeks +0 days and <39 weeks +0 days
• Birth weight appropriate for gestational age (AGA) or Large for Gestational Age (LGA)
• Apgar score 8 or greater
• Children will receive more than 50% of the feeding occasions with human breastmilk
• Mothers will have the intention to exclusively or predominantly breastfeed the subject. On the diary report form mother will report day by day the frequency of human lactation and the frequency and amount of infant formula.
• Readiness and the opportunity for parents to fill out a study diary, questionnaires.
• Parent(s) are willing to postpone major changes in the infant feeding mode, and
• Written informed consent from parents

Exclusion Criteria:

• Older than 24 hours after birth when given the first dose of investigational product
• Any kind of chronic or acute diseases during pregnancy that can modify fecal microbiota in children, e.g. gestational diabetes, pre-clampsia, gastrointestinal disease
• Congenital malformations or anomalies
• Maternal use of antibiotics from gestational week 33 and throughout the study period.
• Maternal use of probiotics from gestational week 33 and throughout the study period.
• Maternal severe obesity at inclusion or at delivery evaluated using Rosso Madrones centiles
• Infant use of antibiotics throughout the study period.
• Infant use of probiotics throughout the study period, including infant formula and/or supplementation.
• Infants carrying out general anesthesia
• Meconium aspiration syndrome
• History of premature disruption of membranes for >24h
• Participation in other clinical trials

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lactobacillus reuteri DSM17038; Lactobacillus reuteri DSM17038, 1x108 CFU once a day for 30 days	Dietary supplement: Lactobacillus reuteri DSM17038; Oil drops of L. reuteri containing 1x10>8 CFU
Placebo Comparator: Placebo probiotics; Placebo for probiotics, pols drops similar in consistency and flavor as experimental product	Other: Placebo for Probiotics; Oil drops mimicking in consistency and flavor to experimental product

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes on fecal microbiome diversity at day 14	Changes on diversity evaluated by Shannon Index of firmicutes, bacteroidetes and actinobacteria at day 14 after intervention	14 days
Changes on fecal microbiome abundance at day 14	Changes on abundance evaluated by Simpson Index of firmicutes, bacteroidetes and actinobacteria at day 14 after intervention	14 days
Changes on fecal microbiome stability at day 14	Changes on stability evaluated by Chao Index of firmicutes, bacteroidetes and actinobacteria at day 14 after intervention	14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes on fecal microbiome diversity at day 7, 30 and 60	Changes on abundance evaluated by Channon Index of firmicutes, bacteroidetes and actinobacteria at day 7, 30 and 60 after intervention	7, 30 and 60 days
Changes on fecal microbiome abundance at day 7, 30 and 60	Changes on abundance evaluated by Simpson Index of firmicutes, bacteroidetes and actinobacteria at day 7, 30 and 60 after intervention	7, 30 and 60 days
Changes on fecal microbiome stability at day 7, 30 and 60	Changes on stability evaluated by Chao Index of firmicutes, bacteroidetes and actinobacteria at day 7, 30 and 60 after intervention	7, 30 and 60 days
Changes on Salivary IgA levels	Levels of salivary IgA after 7,30 and 60 days after intervention	7, 30 and 60 days
Frequency of Adverse Event	Frequency of adverse events reported after randomization and until finish the treatment (day 30)	30 days

Collaborators and Investigators

• Sponsor: Innovacion y Desarrollo de Estrategias en Salud
• Collaborators: BioGaia AB
• Investigators: Principal Investigator: Pedro Gutierrez Castrellon, MD, MSc, DSc, Hospital General Dr. Manuel Gea Gonzalez

Publications and helpful links

General Publications

• Chandel DS, Perez-Munoz ME, Yu F, Boissy R, Satpathy R, Misra PR, Sharma N, Chaudhry R, Parida S, Peterson DA, Gewolb IH, Panigrahi P. Changes in the Gut Microbiota After Early Administration of Oral Synbiotics to Young Infants in India. J Pediatr Gastroenterol Nutr. 2017 Aug;65(2):218-224. doi: 10.1097/MPG.0000000000001522.
• Garcia Rodenas CL, Lepage M, Ngom-Bru C, Fotiou A, Papagaroufalis K, Berger B. Effect of Formula Containing Lactobacillus reuteri DSM 17938 on Fecal Microbiota of Infants Born by Cesarean-Section. J Pediatr Gastroenterol Nutr. 2016 Dec;63(6):681-687. doi: 10.1097/MPG.0000000000001198.
• Nitert MD, Barrett HL, Foxcroft K, Tremellen A, Wilkinson S, Lingwood B, Tobin JM, McSweeney C, O'Rourke P, McIntyre HD, Callaway LK. SPRING: an RCT study of probiotics in the prevention of gestational diabetes mellitus in overweight and obese women. BMC Pregnancy Childbirth. 2013 Feb 25;13:50. doi: 10.1186/1471-2393-13-50.
• Jansman AJ, Zhang J, Koopmans SJ, Dekker RA, Smidt H. Effects of a simple or a complex starter microbiota on intestinal microbiota composition in caesarean derived piglets. J Anim Sci. 2012 Dec;90 Suppl 4:433-5. doi: 10.2527/jas.53850.
• Kuitunen M, Kukkonen K, Juntunen-Backman K, Korpela R, Poussa T, Tuure T, Haahtela T, Savilahti E. Probiotics prevent IgE-associated allergy until age 5 years in cesarean-delivered children but not in the total cohort. J Allergy Clin Immunol. 2009 Feb;123(2):335-41. doi: 10.1016/j.jaci.2008.11.019. Epub 2009 Jan 8.

Study record dates

Study Major Dates

• Study Start (Actual): February 8, 2019
• Primary Completion (Actual): April 18, 2019
• Study Completion (Actual): June 18, 2019

Study Registration Dates

• First Submitted: February 5, 2019
• First Submitted That Met QC Criteria: February 5, 2019
• First Posted (Actual): February 8, 2019

Study Record Updates

• Last Update Posted (Actual): June 20, 2019
• Last Update Submitted That Met QC Criteria: June 18, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Other Study ID Numbers: CSUB0153

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Protocol documents and data base results will be available at international sites
• IPD Sharing Time Frame: January 2019, for 12 months
• IPD Sharing Access Criteria: IPD sharing access will be available for all investigators who want to do secondary analysis, always giving credits to principal investigators and owner of this research
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No