Clinical Trial of L. Reuteri in Infantile Colic 2017

Study Overview
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Brief Summary
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RCT to evaluate the safety and efficacy of Lactobacillus reuteri DSM 17938 to significantly reduce the duration of crying time and fussines in infants from 15days to 4 months of age with colic, feed with human milk (30% sample) or infant formula (70%)

Detailed Description
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RCT to evaluate the safety and efficacy of Lactobacillus reuteri DSM 17938 administrated for 21 days to significantly reduce the duration of crying time and fussines in infants from 15days to 4 months of age with colic. 66 infants feed with human milk and 180 infant feed with infant formula will be included. As primary outcome we will measure the difference between children receiving L. reuteri DSM 17938, 108 CFU vs children receiving placebo regarding average daily crying duration (minutes per day, from average of crying from days 19 to 21 after randomization), measured by Barr diary. Secondary/exploratory outcomes will be average of crying time on day 7 and 14 (Barr diary) of L. reuteri groups vs placebo group; average of crying and fussing time on day 7, 14 and average from days 19 to 21 after randomization (Barr diary) of L. reuteri groups vs placebo group; responders percentage on day 7, 14 and 21, decrease in daily average crying time of 50% during the study; QoL (PedsQL-2.0-Family Impact Module AU2.0 spa-MX) changes from baseline to days 7, 14 and 21 and Edinburg postnatal depression scale for mothers from baseline to days 7, 14 and 21

Official Title
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Safety and Efficacy of Lactobacillus Reuteri DSM 17938 to Reduce the Crying Time in Infants With Colic: Randomised Controlled Trial With Two Parallel Arms. Version 3.3. Nov,11th,2016

Conditions
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Infantile Colic

Intervention / Treatment
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* Dietary Supplement: L. reuteri DSM 17938 in drops
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Younger than 10 weeks of age Full term infant (37-42 weeks gestational age) Birth weight ≥ 2,500g Apgar score ≥ 7 at 5 minutes Infantile colic diagnosed according to modified Wessel's criteria (crying more than 180 min/day during 3 days for at least a week prior to enrolment) Parental motivation to postpone changes in the infant feeding mode, unless necessary Stated availability throughout the study period Parent(s) willingness and ability to fill out charts and questionnaires Signed informed consent Exclusion Criteria: Failure to thrive Chronic illness or major medical problem Gastrointestinal disease Use of any antibiotic 2 weeks before Day 1 in the study. This applies also to lactating mothers whose infants participate in the trial Use of supplements/eaten foods that contain Lactobacillus reuteri, 2 weeks before Day 1 Use of proton pump inhibitors in the week (7 days) prior to enrolment If breastfeeding, use of probiotic by the mother in the week (7 days) prior to enrolment and throughout the study period Use of infant formula with hydrolysed protein Infant receiving solid foods (such as cereals, mashed fruits or vegetable purée) Change of feeding mode planned by parents during the study period

Ages Eligible for Study
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Minimum Age: 1 Week
Maximum Age: 9 Weeks

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
Interventional Model Description: Randomized controlled trial, double blind allocation concealment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HMilkProb<br>L. reuteri DSM 17938 in drops will be given at a dose of 5 drops containing 1x108 colony-forming units (CFU) once time per day in an oil formulation delivered from a drop bottle. In the active study product, freeze-dried L. reuteri is suspended in a mixture of pharmaceutical grade medium chain triglycerides and sunflower oil together to give the product the correct rheological properties | Dietary Supplement: L. reuteri DSM 17938 in drops<br>* L. reuteri DSM 17938 will be given at a dose of 5 drops containing 1x108 colony-forming units (CFU) once time per day in an oil formulation delivered from a drop bottle<br>|
| Placebo Comparator: HMilkPlacebo<br>The placebo consists of an identical formulation except that the L. reuteri is not present | Other: Placebo<br>* The placebo consists of an identical formulation except that the L. reuteri is not present<br>|
| Experimental: IFormProb<br>L. reuteri DSM 17938 in drops will be given at a dose of 5 drops containing 1x108 colony-forming units (CFU) once time per day in an oil formulation delivered from a drop bottle. In the active study product, freeze-dried L. reuteri is suspended in a mixture of pharmaceutical grade medium chain triglycerides and sunflower oil together to give the product the correct rheological properties | Dietary Supplement: L. reuteri DSM 17938 in drops<br>* L. reuteri DSM 17938 will be given at a dose of 5 drops containing 1x108 colony-forming units (CFU) once time per day in an oil formulation delivered from a drop bottle<br>|
| Placebo Comparator: IFormPlacebo<br>The placebo consists of an identical formulation except that the L. reuteri is not present | Other: Placebo<br>* The placebo consists of an identical formulation except that the L. reuteri is not present<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Crying time | Difference between children receiving L. reuteri DSM 17938, 108 CFU vs children receiving placebo regarding average daily crying duration (minutes per day, from average of crying from days 19 to 21 after randomization), measured by Barr diary. Difference between children receiving L. reuteri DSM 17938, 108 CFU vs children receiving placebo regarding average daily crying duration (minutes per day, from average of crying from days 19 to 21 after randomization), measured by Barr diary. | 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Preliminary crying time | Average of crying time on day 7 and 14 (Barr diary) of L. reuteri groups vs placebo group | Day 7 and 14 | 
| Crying and fussing | Average of crying and fussing time on day 7, 14 and average from days 19 to 21 after randomization (Barr diary) of L. reuteri groups vs placebo group | 7,14 and 21 days | 
| Total responders | Responders percentage on day 7, 14 and 21, decrease in daily average crying time of 50% during the study | 7,14 and 21 days | 
| Impact on Quality of Life | Impact on Quality of Life measured by PedsQL-2.0-Family Impact Module AU2.0 spa-MX. Changes from baseline to days 7, 14 and 21 | 7, 14 and 21 days | 
| Maternal depression | Maternal depression evaluated with Edinburgh Postnatal Depression Scale (EPDS) | 7, 14 and 21 days |