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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Colic

Intervention / Treatment
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* Biological: Biogaia L. reuteri DSM 17938
* Biological: Probiotic Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy term infant 21-90 days of age Birth weight ≥2500 g Exclusively breastfed (to reduce variability in the intestinal microflora attributable to dietary variations) With colic symptoms (>3 hours of crying on >3 days per week) with debut 10 ± 5 days before enrollment Gestational age between 37 and 42 weeks Apgar score higher than 7 at 5 minutes Written informed consent from a parent Exclusion Criteria: Any chronic illness or gastrointestinal disorder as judged by the pediatrician Any history of antibiotic treatment or probiotic supplementation Failure to obtain a written consent by parent/legal guardian Participation in other clinical trials Infants with acute illness Subjects with allergies or family history of allergies to any of the ingredients of the study product or placebo

Ages Eligible for Study
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Minimum Age: 21 Days
Maximum Age: 180 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Biogaia L. reuteri DSM 17938<br>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<br>* Freeze-dried Lactobacillus reuteri DSM 17938 suspended in oil. Brand Name Active Agent: BioGaia™<br>|
| Placebo Comparator: Probiotic Placebo<br>Placebo drops (sunflower oil, medium chain triglyceride oil, silicon chloride), 5 drops, once a day for 21 days. | Biological: Probiotic Placebo<br>* Description of Placebo: contains same excipients as Active Agent, without the active ingredient<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pediatric, infantile colic, probiotic treatment