The Use of Lactobacillus Reuteri in Functional Constipation in Children

The Use of Lactobacillus Reuteri in Functional Constipation in Children: A Double Blind Randomized Control Trial

Functional constipation (FC) is a common condition in childhood, with an estimated prevalence of 0.7% to 29%.The diagnosis and treatment of FC can be difficult tasks, and children are often referred to specialist services causing treatment to become expensive and time-consuming.The standard treatment based on osmotic laxatives (mainly PEG). The recovery rate is 50% to 60% after 1 year of treatment, with 50% of the children having relapse within 5 years. Studies in adults have established the effectiveness of some lactic acid bacteria in the treatment of chronic constipation.

Study Overview

• Status: Terminated
• Conditions: Functional Constipation
• Intervention / Treatment: Dietary supplement: probiotic - Lactobacillus reuteri; Other: placebo - with no active ingredient

Detailed Description

Functional constipation (FC) is a common condition in childhood, with an estimated prevalence of 0.7% to 29%.The diagnosis and treatment of FC can be difficult tasks, and children are often referred to specialist services causing treatment to become expensive and time-consuming.The standard treatment based on osmotic laxatives (mainly PEG). The recovery rate is 50% to 60% after 1 year of treatment, with 50% of the children having relapse within 5 years. Studies in adults have established the effectiveness of some lactic acid bacteria in the treatment of chronic constipation.However, it is unclear whether similar effects occur in children. Lactobacilli and Bifidobacteria are the most studied species showing a high safety profile. Both are able to promote colonic peristalsis which could be beneficial for the treatment of constipation .Even though traditional treatment is well established and safe, high proportion of children need prolonged treatment for several months or even years. For many parents there is a concern regarding prolonged treatment with PEG .Lactobacilli, bifidobacteria and FOS (fructooligosaccharide) increase stool frequency and decrease consistency in healthy adults and therefore could prevent recurrence of constipation after PEG withdrawal .The principle investigator hypothesize that treatment with probiotics adjunct to PEG and several months thereafter could decrease the proportion of children needed permanent or prolonged treatment (>12 months) with PEG.

The importance of the study and its practical benefits:

Treatment with PEG for FC is well established and is considered safe. Despite that, a high proportion of children need prolonged treatment for several months or even years. For many parents there is a concern regarding prolonged treatment with PEG. Previous studies did not demonstrate efficacy of treatment with probiotics or prebiotics in FC. Neither of these studies assessed effectiveness probiotics/prebiotic products as adjunct to the traditional treatment (PEG) of FC in shortening its period.

A recently published studies including from Israel, demonstrated efficacy of Lactobacillus reuteri in irritable bowel syndrome, infantile colic and functional abdominal pain .Therefore, demonstration of positive effect of treatment with probiotic product in FC, could imply for potential use of this product in other functional gastrointestinal disorders among children.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Israel
  • Afula, Israel
    • Emek Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 15 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 0.5 - 15 years
• Diagnosis of functional constipation according to Rome IV criteria

Exclusion Criteria:

• Children with chronic diseases which could cause constipation: Celiac disease, food allergy, Hypothyroidism, Inflammatory Bowel Disease, electrolytes disturbances, Cystic fibrosis, Hirschsprung disease, Neuropathic conditions (Spinal cord trauma, Neurofibromatosis, Tethered cord) or intestinal pseudo-obstruction.
• Prematurity (< 34 weeks)
• S/P intestinal surgery
• Children treated with medications associated with constipation.
• Existing malignancy
• Primary or secondary immunodeficiency

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Treatment Arm; 25 consecutive children diagnosed with functional constipation will be treated with full dose PEG (Polyethylene glycol 3350) treatment (dose of ~1g/kg/day) for 12 weeks. After 12 weeks of treatment they will be randomized: treated arm will receive probiotic containing Lactobacillus reuteri for 12 weeks while tapering the PEG dose Dose of 5 drops per day for 48 weeks	Dietary supplement: probiotic - Lactobacillus reuteri; The treated arm will receive 5 drops per day for 48 weeks
Placebo Comparator: Placebo Arm; 25 consecutive children diagnosed with functional constipation will be treated with full dose PEG (Polyethylene glycol 3350) treatment (dose of ~1g/kg/day) for 12 weeks. After 12 weeks of treatment they will be randomized: control arm will receive placebo for 12 weeks while tapering the PEG dose Dose of 5 drops per day for 48 weeks	Other: placebo - with no active ingredient; The control arm will receive 5 drops per day for 48 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The prevalence of constipation recurrence	according to Rome IV criteria	This measure will be assessed at weeks 24.
The prevalence of constipation recurrence	according to Rome IV criteria	This measure will be assessed at weeks 60.
failure of maintaining normal bowel movements without PEG and the need to resume PEG treatment	according to Rome IV criteria	This measure will be assessed at weeks 24.
failure of maintaining normal bowel movements without PEG and the need to resume PEG treatment	according to Rome IV criteria	This measure will be assessed at weeks 60.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The number of bowel movements per week	The investigator will collect the information during the following visits from the patient	This measure will be assessed at baseline and at 24, 36, 48 and 60 weeks after enrolment
The number of episodes of fecal incontinence per week	The investigator will collect the information during the following visits from the patient	This measure will be assessed at baseline and at 24, 36, 48 and 60 weeks after enrolment
The stool consistency in patients without PEG treatment	The investigator will collect the information during the following visits from the patient	This measure will be assessed at baseline and at 24, 36, 48 and 60 weeks after enrolment

Collaborators and Investigators

• Sponsor: HaEmek Medical Center, Israel

Study record dates

Study Major Dates

• Study Start (Actual): June 26, 2018
• Primary Completion (Actual): June 26, 2018
• Study Completion (Actual): June 26, 2018

Study Registration Dates

• First Submitted: October 10, 2017
• First Submitted That Met QC Criteria: November 3, 2017
• First Posted (Actual): November 6, 2017

Study Record Updates

• Last Update Posted (Actual): October 4, 2018
• Last Update Submitted That Met QC Criteria: October 2, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Constipation
• Other Study ID Numbers: 0042-17-EMC

Drug and device information, study documents

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