Effects on Crying Time in Colicky Infants With the Supplementation of Lactobacillus Reuteri DSM 17938

Study Overview
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Brief Summary
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Infant colic is a common condition characterized by excessive crying. The otherwise healthy infant aged less than 3 months is difficult to console during the periods with crying. The condition is defined by modified Wessel's criteria i.e. crying for more than 3 hours of the day, for more than 3 days of the week for at least 1 week. The description of infant colic hasalso been defined by Rome III diagnostic criteria andincludes infants from birth to 4 months of age,without failure to thrive, that are showing paroxysms of irritability, fussing or crying that starts and stops without obvious cause. The episodes last 3 or more hours/day and occur at least 3days/week for at least one week. The infant has no signs of central nervous system or intrinsic developmental difficulties, is normal on physical examination, and has normal growth patterns. Although infant colic is considered to be self limiting it is a distressing problem for families. It is in fact one of the most common reasons why parents seek the advice of a paediatrician or family practitioner during their child's first 3 months of life Up to 20% of infants under three months are affected by infant colic. Infant colic could have significant adverse effects on family quality of life and could even be a trigger for shaken baby syndrome. Parental perception associated with colicky complaints is therefor strongly recommended to be an outcome measure in trials of infantile colic. Measurement of parental/family quality of life and parental perception of colic severity with the help of a Visual Analogue Scale (VAS) in a Polish study showed that the use of a probiotic, Lactobacillus reuteri DSM 17938, could improve the perceived problems. The relationship between infant colic and gastroenterological, allergical and psychological disorders later in childhood was studied in a prospective study on 96 infants divided into two groups, colicky and non-colicky. The children diagnosed with infant colic, showed an increased susceptibility to recurrent abdominal pain, allergic and psychological disorders in childhood when they were 10 years old. The aetiology of infantile colic seems to be multifactorialbut is,despite many years of research, still unknown. The intestinal microbiota differs between infants with and without colic and has therefore been suggested to have a potential role. Other possible explanations are for example gut motility disturbances, low-grade mucosal inflammation and visceral hypersensitivity. Evidence suggests thatadministration of the probioticL. reuteri DSM 17938 might offer some benefit.L. reuteri DSM 17938 has been tested for its effect on crying in colicky infants and has been demonstrated to have a significantly favourable effect on crying time in fivetrials. One is a randomized trial that compared the probioticto Simethicone; three areplacebo controlled randomized double blind trials and yet another is a placebo controlled randomized, single blind, observational study. A fifth studydid not find any effect. Combining the results in a meta-analysis from three double blind, placebo controlled randomized trials (published at the time of the analysis, including the neutral one) found that, compared with placebo, L. reuteri administration reduced crying time at day 21 with about 40 min. Recently it has been documented in a clinical trial that prophylactic use of L. reuteriDSM 17938during the first three months of lifereduced the onset offunctional gastrointestinal disorders, particularly functional constipation, regurgitation and infantile colic. In conclusion, the administration L. reuteri DSM 17938 may reduce the crying time in children with infantile colic, especially those fed predominantly or exclusively with breast milk. However, further randomized controlled studies, are required to be able develop recommendations in the management of infant colic. The present trial is undertaken to further document the effect of L. reuteri DSM 17938 on crying in colicky infants.

Official Title
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Effects on Crying Time in Colicky Infants With the Supplementation of Lactobacillus Reuteri DSM 17938: A Randomized, Double Blind, Placebo-controlled Study

Conditions
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Crying Time in Colicky Infants

Intervention / Treatment
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* Drug: L. reuteri DSM 17938
* Other: The placebo consists of an identical formulation without L. reuteri DSM 17938


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis according to modified Wessel's definition of infant colic i.e. crying for more than 3 hours of the day, for more than3 days of the week Full term infant, i.e. gestational age between 37 and 42 weeks Breast fed, either exclusively or predominantly, i.e. to more than 50% Birth weight 2500 - 4000g. Apgar score ≥7 at 5 minutes at birth Age from birth to 4 months of age 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 Failure to thrive Use of antibiotics two weeks before randomisation and throughout the intervention period, both infant and mother Use of probiotics two weeks before randomisation and throughout the intervention period, both infant (infant formula and/or supplementation)and mother Use of proton pump inhibitors two weeks before randomisation and throughout the intervention period. Infant receiving solid foods, such as cereals, mashed fruits or vegetable puree Participation in other clinical trials

Ages Eligible for Study
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Maximum Age: 4 Months

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: L. reuteri DSM 17938 group<br>L. reuteri DSM 17938 will be given at a dose of 100000000 colony forming units (CFU) 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 with pharmaceutical grade silicon dioxide to give the product the correct rheological properties. Each day, at about the same time, the infants will be given 5 drops (1x100000000 CFU) of the study product in connection with feeding. | Drug: L. reuteri DSM 17938<br>* Effects on crying time in colicky infants with the supplementation of Lactobacillus reuteri DSM 17938<br>|
| Placebo Comparator: Placebo group<br>The placebo consists of an identical formulation without L. reuteri. Each day, at about the same time, the infants will be given 5 drops placebo in connection with feeding. | Other: The placebo consists of an identical formulation without L. reuteri DSM 17938<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Daily crying time will be measured at Day 7 through questionnaire finished by parents. | 50 evaluable infants in each group will be needed to detect (i.e. get a two-sided p-value less than 5%) a 50 minutes difference in crying time between L. reuteri DSM 17938 and placebo group and with a 90 minutes standard deviation, and a power of 80%, two-sided hypothesis. | Day 7 | 
| Daily crying time will be measured at Day 14 through questionnaire finished by parents. | 50 evaluable infants in each group will be needed to detect (i.e. get a two-sided p-value less than 5%) a 50 minutes difference in crying time between L. reuteri DSM 17938 and placebo group and with a 90 minutes standard deviation, and a power of 80%, two-sided hypothesis. | Day 14 | 
| Daily crying time will be measured at Day 21 through questionnaire finished by parents. | 50 evaluable infants in each group will be needed to detect (i.e. get a two-sided p-value less than 5%) a 50 minutes difference in crying time between L. reuteri DSM 17938 and placebo group and with a 90 minutes standard deviation, and a power of 80%, two-sided hypothesis. | Day 21 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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crying, colicky, infants, Lactobacillus reuteri DSM 17938