Lactobacillus Reuteri DSM 17938 Versus Placebo in the Treatment of Infantile Colic

Lactobacillus Reuteri DSM 17938 Versus Placebo in the Treatment of Infantile Colic: A Randomized Double-blind Controlled Trial

Infantile colic is a common medical condition which remains a frustrating problem for parents and health care providers with no clear treatment guidelines. To fill the void in existing literature, we present a protocol to examine whether probiotics are effective in decreasing infantile colic symptoms when compared to placebo treatment.

We hypothesize that oral administration of the probiotic L. reuteri DSM 17938 will reduce symptoms of infantile colic in breastfed infants in comparison to placebo.

An interim analysis will be conducted after 50 infants randomized to monitor both safety and efficacy.

Study Overview

• Status: Completed
• Conditions: Colic
• Intervention / Treatment: Biological: Biogaia L. reuteri DSM 17938; Biological: Probiotic Placebo

Detailed Description

Infantile colic is one of the most commonly reported medical problems within the first three months of life causing appreciable distress for both parents and pediatricians. The reported incidence of infantile colic ranges from 3% to 28% in prospective studies and up to 40% in retrospective surveys.

The pathogenesis of infantile colic remains elusive despite decades of research. It appears that multiple independent origins might be involved: amongst them infant's difficult temperament, inadequate mother-infant communication or maternal anxiety, transient lactase deficiency, exposure to cow's milk, abnormal gastrointestinal function, maternal smoking during pregnancy or after delivery. Consequently, various treatment approaches have been tried to alleviate this condition.

Recent studies have suggested that changes of intestinal microflora of a newborn may play an important role in pathogenesis of infantile colic. Therefore, dietary supplementation with probiotics has been proposed for the improvement of this condition.

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5V1X8
      • The Hospital for Sick Children

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 2 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Healthy term infant 21-90 days of age
2. Birth weight ≥2500 g
3. Exclusively breastfed (to reduce variability in the intestinal microflora attributable to dietary variations)
4. With colic symptoms (>3 hours of crying on >3 days per week) with debut 10 ± 5 days before enrollment
5. Gestational age between 37 and 42 weeks
6. Apgar score higher than 7 at 5 minutes
7. Written informed consent from a parent

Exclusion Criteria:

1. Any chronic illness or gastrointestinal disorder as judged by the pediatrician
2. Any history of antibiotic treatment or probiotic supplementation
3. Failure to obtain a written consent by parent/legal guardian
4. Participation in other clinical trials
5. Infants with acute illness
6. Subjects with allergies or family history of allergies to any of the ingredients of the study product or placebo

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
Experimental: Biogaia L. reuteri DSM 17938; Biogaia L. reuteri DSM 17938, probiotic infant drops (5 drops=10^8 cfu),5 drops, once per day for 21 days.	Biological: Biogaia L. reuteri DSM 17938; Freeze-dried Lactobacillus reuteri DSM 17938 suspended in oil. Brand Name Active Agent: BioGaia™
Placebo Comparator: Probiotic Placebo; Placebo drops (sunflower oil, medium chain triglyceride oil, silicon chloride), 5 drops, once a day for 21 days.	Biological: Probiotic Placebo; Description of Placebo: contains same excipients as Active Agent, without the active ingredient

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change in crying time	Reduction of daily median crying time (measured with parental diary) with L. reuteri DSM 17938 versus placebo at any of the time points 7, 14, and 21 days	Baseline, 7 days, 14 days, 21 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of responders vs. non-responders	Number of responders versus non-responders with L. reuteri versus placebo at the time points 7, 14, and 21 days. Responder is defined as a decrease in daily average crying time of 50% during the study as measured using the maternal daily diary.	Baseline, at 7, 14 and 21 days
Parental quality of life	Parental quality of life assessed by self-administered numerical rating scale from 0 (worst possible) to 10 (perfect well-being)	Daily for 21 days
Number of episodes of crying	Reduction in the number of episodes of crying (measured with parental diary) with L. reuteri DSM 17938 versus placebo	Over 21 days
Duration of episodes of crying	Reduction in the duration of episodes of crying (measured with parental diary) with L. reuteri DSM 17938 versus placebo	Over 21 days
Changes in stool consistency		Over 21 days

Collaborators and Investigators

• Sponsor: The Hospital for Sick Children
• Investigators: Principal Investigator: Gideon Koren, MD, The Hospital for Sick Children

Publications and helpful links

General Publications

• Chau K, Lau E, Greenberg S, Jacobson S, Yazdani-Brojeni P, Verma N, Koren G. Probiotics for infantile colic: a randomized, double-blind, placebo-controlled trial investigating Lactobacillus reuteri DSM 17938. J Pediatr. 2015 Jan;166(1):74-8. doi: 10.1016/j.jpeds.2014.09.020. Epub 2014 Oct 23.

Helpful Links

• Probiotics for Infantile Colic: A Randomized, Double-Blind, Placebo-Controlled Trial Investigating Lactobacillus reuteri DSM 17938

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): June 1, 2014

Study Registration Dates

• First Submitted: February 23, 2012
• First Submitted That Met QC Criteria: February 28, 2012
• First Posted (Estimate): February 29, 2012

Study Record Updates

• Last Update Posted (Estimate): November 20, 2014
• Last Update Submitted That Met QC Criteria: November 19, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Keywords: pediatric; infantile colic; probiotic treatment
• Additional Relevant MeSH Terms: Infant, Newborn, Diseases; Colic
• Other Study ID Numbers: 1000018504