Effect of L. Reuteri on Bowel Movements in Children (BIOWELL Study) (BIOWELL)

Randomised Controlled Trial With Two Parallel Arms Testing the Effect of L. Reuteri on Bowel Movements in Children Aged 6 Months to 4 Years

A randomized, multicenter, placebo-controlled, double blind study in two parallel groups testing the efficacy of daily oral supplementation with the probiotic L.reuteri DSM17938 compared to placebo in increasing the number of spontaneous bowel movements in infants and children with functional constipation.

Study Overview

• Status: Completed
• Conditions: Constipation
• Intervention / Treatment: Dietary supplement: L.reuteri; Drug: Placebo

Detailed Description

Functional constipation in infants up to 4 years of age is defined according to Rome III criteria (Hyman 2006). The diagnose must include 1 month of at least two of the following criteria: two or fewer defecations per week; at least 1 episode per week of incontinence after the acquisition of toilet skills; history of excessive stool retention; history of painful or hard bowel movements; presence of a large faecal mass in the rectum; history of large-diameter stools that may obstruct the toilet.

Accompanying symptoms may include irritability, decreased appetite and/or early satiety. The accompanying symptoms disappear immediately following passage of a large stool.

There is a growing interest for the use of probiotics in functional constipation as research suggests that probiotics could provide beneficial support in the traditional treatment arsenal although the mechanisms of actions are not completely understood.

Wu et al have demonstrated that Lactobacillus reuteri DSM 17938 may have a region-specific intestinal effect on gut motility and therefore could be beneficial in treatment of constipation

Lactobacillus reuteri DSM 17938 has shown significant favourable effects in adults (Ojetti 2014) and young children as described above (Coccorullo 2010, Olgac 2013). These studies require confirmation however. The present clinical study has been designed to strengthen the current available data that L. reuteri DSM 17938 has beneficial effects in infants and young children with functional constipation.

We hypothesize that daily oral supplementation with the probiotic Lactobacillus reuteri DSM 17938 will effectively increase the number of spontaneous bowel movements in infants/children diagnosed with functional constipation according to Rome IV.

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Corbeil-Essonnes, France
    • CH SUd Francilien
  • Créteil, France, 94000
    • CHI Créteil
  • Le Havre, France
    • Hôpital J. Monod - Pavillon Femme Mère Enfant - Le Havre
  • Lille, France
    • Hôpital Saint Vincent-de-Paul
  • Paris, France
    • CHU Robert Debré

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 months to 2 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age: 6 months up to 4 years
• Suffering from functional constipation, as defined by modified Rome III criteria for children aged 4 years or less (Hyman 2006)
• Parent(s) willingness to postpone major changes in the infant feeding mode
• Parent(s) willingness and ability to fill in diary and questionnaires
• Written informed consent from parents
• Stated availability throughout the study period

Exclusion Criteria:

• Chronic illness or major medical problem
• Gastrointestinal disease (including organic cause of constipation and dyschezia or history of severe fecalome)
• Intractable constipation (not responding to conventional treatment for more than 3 months)
• Gastrointestinal surgery (in the year before enrolment)
• Food allergy, lactose or gluten intolerance, as declared by parents
• Use of L. reuteri two weeks before randomisation and throughout the intervention period. If fed with infant formula, it cannot contain L. reuteri.
• Use of antibiotics two weeks before randomisation and throughout the intervention period, both infant/child and lactating mother
• If breastfeeding, use of L reuteri by the mother 2 weeks prior to enrolment
• Conventional treatment for constipation within 2 weeks before enrolment
• Medication that influences gastrointestinal motility
• Mental or behavioral disorders as judged by the investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: L.reuteri; probiotics: L.reuteri produced by Biogaia 5 drops per day: 10exp(8) colony forming unit will be delivered	Dietary supplement: L.reuteri; Each day, at about the same time, the subjects will be given 5 drops (1x10^8 CFU) of the study product in connection with feeding; Other Names: Lactobacillus reuteri
Placebo Comparator: Placebo; Same formulation as probiotics, without active substance. 5 drops per day will be delivered	Drug: Placebo; Same formulation as study product, without probiotics.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in number of spontaneous bowel movements	Change in number of spontaneous bowel movements at week 4 compared to baseline evaluated by a bowel habit questionnaire (BQH)	Week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
rescue medication	Total number of rescue medication during the intervention period	week 4
fecal retention	number of subjects with 3 or more than 3 stools per week and without fecal retention at the last week of the intervention period	week 4
weekly number of spontaneous bowel movements	weekly number of spontaneous bowel movements evaluated by the Bowel habit Questionnaire	week 1
weekly number of spontaneous bowel movements	weekly number of spontaneous bowel movements evaluated by the Bowel habit Questionnaire	week 2
weekly number of spontaneous bowel movements	weekly number of spontaneous bowel movements evaluated by the Bowel habit Questionnaire	week 3
weekly number of spontaneous bowel movements	weekly number of spontaneous bowel movements evaluated by the Bowel habit Questionnaire	week 4
weekly number of spontaneous bowel movements	weekly number of spontaneous bowel movements evaluated by the Bowel habit Questionnaire	week 8
Score of QOL	Score of quality of life measured using the PedsQL Parent family acute version	baseline
Score of QOL	Score of quality of life measured using the PedsQL Parent family acute version	week 4
Score of QOL	Score of quality of life measured using the PedsQL Parent family acute version	week 8
Pain during defecation	Score of pain during defecation measured using Hick or Wong baker faces	baseline
Pain during defecation	Score of pain during defecation measured using Hick or Wong baker faces	week 4
Pain during defecation	Score of pain during defecation measured using Hick or Wong baker faces	week 8

Collaborators and Investigators

• Sponsor: Centre Hospitalier Intercommunal Creteil
• Collaborators: BioGaia AB

Publications and helpful links

General Publications

• Jung C, Kalach N, Degas V, Jeridi Y, Bertrand V, Bellaiche M. Effect of L. reuteri on bowel movements in children aged 6 months to 4 years: A double-blind randomized controlled trial. Front Pediatr. 2022 Oct 26;10:997104. doi: 10.3389/fped.2022.997104. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2017
• Primary Completion (Actual): June 30, 2021
• Study Completion (Actual): July 30, 2021

Study Registration Dates

• First Submitted: January 23, 2017
• First Submitted That Met QC Criteria: January 24, 2017
• First Posted (Estimate): January 25, 2017

Study Record Updates

• Last Update Posted (Actual): June 13, 2022
• Last Update Submitted That Met QC Criteria: June 9, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: probiotics; constipation; Lactobacillus reuteri
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Constipation
• Other Study ID Numbers: BIOWELL; 2016-A00419-42 (Other Identifier: ID-RCB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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