Clinical trial NCT03030664: Effect of L. Reuteri on Bowel Movements in Children (BIOWELL Study)
Official title: Randomised Controlled Trial With Two Parallel Arms Testing the Effect of L. Reuteri on Bowel Movements in Children Aged 6 Months to 4 Years
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Constipation
Keywords: constipation
Lactobacillus reuteri
probiotics
Lead sponsor: Centre Hospitalier Intercommunal Creteil
Sponsor class: OTHER
Collaborators: name: BioGaia AB
First posted: 2017-01-25
Enrollment: 52
Sex: ALL
Minimum age (years): 6
Maximum age (years): 4
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in number of spontaneous bowel movements
timeFrame: Week 4
Secondary outcomes:
measure: rescue medication
timeFrame: week 4
measure: fecal retention
timeFrame: week 4
measure: weekly number of spontaneous bowel movements
timeFrame: week 1
measure: weekly number of spontaneous bowel movements
timeFrame: week 2
measure: weekly number of spontaneous bowel movements
timeFrame: week 3
measure: weekly number of spontaneous bowel movements
timeFrame: week 4
measure: weekly number of spontaneous bowel movements
timeFrame: week 8
measure: Score of QOL
timeFrame: baseline
measure: Score of QOL
timeFrame: week 4
measure: Score of QOL
timeFrame: week 8
measure: Pain during defecation
timeFrame: baseline
measure: Pain during defecation
timeFrame: week 4
measure: Pain during defecation
timeFrame: week 8
Other outcomes:
Locations:
city: Corbeil-Essonnes
country: France
facility: CH Sud francilien
city: Créteil
country: France
facility: CHI Creteil
city: Le Havre
country: France
facility: Hôpital J. Monod - Pavillon Femme Mère Enfant - Le Havre
city: Lille
country: France
facility: Hôpital Saint Vincent-de-Paul
city: Paris
country: France
facility: CHU Robert Debré
Study officials:
affiliation: Hopital Universitaire Robert-Debre
name: Marc BELLAICHE, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.