Efficacy of an Oral Rehydration Solution Containing the Probiotic Lactobacillus Reuteri Protectis and Zinc in Infants With Acute Gastroenteritis

Study Overview
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Brief Summary
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An ORS with L. reuteri DSM 17938 and zinc is expected to reduce duration and severity of symptoms in infants and young children with acute gastroenteritis.

Detailed Description
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Oral rehydration solution is recommended for treatment and prevention of dehydration due to acute gastroenteritis in infants and children (WHO/UNICEF, 2004; ESPGHAN / ESPID Guidelines, 2008). Acute diarrhoea may lead to zinc depletion in infants, and zinc supplementation is recommended in infants and children with acute gastroenteritis living in developing countries. In developed countries however, the studies on the efficacy of zinc supplementation in children with acute gastroenteritis are few and conflicting. Selected strains of probiotics, including L. reuteri ATCC 55730, have been shown in several studies to reduce the duration and the severity of diarrhoea in children with acute gastroenteritis and the effect is greater if the probiotics are given within 60 hours from the onset of symptoms. Lactobacillus reuteri (L. reuteri) has been shown to reduce the duration and severity of acute gastroenteritis in children aged 6-36 months. In these studies L. reuteri was reported to have clinical effect on diarrhoea of both bacterial and viral (rotavirus) origin. Furthermore, L. reuteri strain DSM 17938 has recently been shown to reduce the duration of watery diarrhoea by 1.2 days among 6-36 mo old Italian children with acute gastroenteritis treated in hospital. The present study is a prospective, randomized, double blind, controlled study with parallel groups. The planned investigation is designed to compare the efficacy of an ORS with L. reuteri DSM 17938 and zinc to an ORS with similar osmolarity and content of salts but without L. reuteri DSM 17938 and zinc, on the duration and severity of acute gastroenteritis. 92 children aged 6-36 months seen at private pediatric clinics and/or at the emergency clinics of the Athens Childrens Hospital AGIA SOPHIA, and treated either as outpatients or as inpatients will be recruited until the final sample size is reached. Assuming a difference of 30% between groups in the primary outcome of prevalence of diarrhoea on day 2, and estimating an attrition rate of approximately 15%, the final sample size will be 92 subjects, or 46 subjects in each arm. Data collection points will be on day 7 at the outpatient clinic of the Division of Pediatric Gastroenterology & Nutrition of the First Department of Paediatrics, Athens University Hospital.

Conditions
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Acute Gastroenteritis

Intervention / Treatment
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* Dietary Supplement: ORS rehydration solution
* Dietary Supplement: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 6 - 36 months old children 3 or more watery or soft stools per day for the past 24-48 hours Clinically judged as having mild to moderate dehydration (Bailey scale scores 1 to 4) Available throughout the study period Re-examination on the 7th day from the enrolment The signed informed consent by one/both parents or legal guardian Parents or legal guardian should have the mental ability to understand and willingness to fulfil all the details of the protocol Exclusion Criteria: Diarrhoea lasting more than 48 h Clinical signs of severe dehydration (Bailey scale scores = or > 5) Malnutrition as judged by a body weight/height ratio below the 5th percentile Clinical signs of a coexisting severe acute systemic illness (meningitis, sepsis, pneumonia) Immunodeficiency Severe chronic disease including cystic fibrosis Food allergy diagnosed by physician or other chronic gastrointestinal diseases Use of pre-/probiotics in the previous 2 weeks, for example infant formula containing probiotics and/or prebiotics. Use of antibiotics or any anti-diarrhoeal medication in the previous 4 weeks

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 36 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ORS with probiotic and zinc<br>ORS with probiotic and zinc Oral rehydration solution with freeze-dried Lactobacillus reuteri DSM 17938 and zinc sulphate | Dietary Supplement: ORS rehydration solution<br> <br> |
| Placebo Comparator: Placebo Comparator<br>Standard oral rehydration solution | Dietary Supplement: placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resolution of diarrhoea. | Proportion of children without watery (3A ISS by Amsterdam infant stool scale ) or soft (3B ISS Amsterdam infant stool scale) stools on day 2 of treatment. Day 0 = day of enrolment and start of treatment, day 1 = first complete day of treatment Time from start of treatment and until last watery or soft stool. | 48 hrs after start of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of severity of diarrhoea | Reduction of severity of diarrhoea will be evaluated as though : Number of watery (type 3A ISS ) and soft ( 3B ISS) stools daily on each of the day of the therapy and up to 5 days. Proportion of children with watery (3A ISS) and soft ( 3B ISS) stools on each of the day 1-5 (Day 0 = day of enrolment and start of treatment, day 1 = first complete day of treatment) Νumber of vomiting episodes: per child on each of the treatment days 1-5. Volume of ORS intake during the first 24h of treatment. Need of hospitalization Absence of workdays for the parents. Child's absence from day care / nursery. Medication needed for treatment of diarrhoea. | 120 hrs from the start on treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute gastroenteritis, Probiotics, Lactobacillus reuteri, Zinc supplementation, Infants, Age 6 months to 36 months