Human Milk Oligosaccharides and Childhood Diarrhoea

Study Overview
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Brief Summary
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Assessment of the impact of oral Human Milk Oligosaccharides (HMO) application on acute diarrhoea and the development of prolonged and persistent diarrhoea in paediatric patients hospitalized with acute diarrhoea.

Detailed Description
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The trial is single site, double blind, randomized of HMO addition (1.5 g /day) to standard of care in paediatric diarrhoea patients. HMO application and follow-up of the children at home will be done for 2 weeks. Control patients receive only the standard of care (ORS plus zinc). A breastfed group of diarrhoea patients will serve as reference group. The total sample size is 495 patients. Patients will be females and males aged 6 months to 2 years old with acute diarrhoea.

Official Title
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Treatment of Acute Childhood Diarrhoea With Human Milk Oligosaccharides and Impact on Gut Micro Biota Dysbiosis and Nutritional Status

Conditions
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Acute Diarrhea

Intervention / Treatment
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* Other: Oral rehydration solution
* Other: Zinc
* Other: Human milk oligosaccharides
* Other: Breastfeeding


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Non breast-fed children (group I and group II): Both male and female children between the ages of 6 months to 2 years. Acute diarrhoea (<48 hours) without interfering co-morbidities, e.g. acute respiratory tract infection, sepsis, gross electrolyte imbalances etc. Guardian is willing to have the child admitted to the hospital as an inpatient until resolution of diarrhea and to return to the clinic with the child on Day 14 after admission for a final evaluation. Written informed consent must be obtained prior to admission to this study. The subject has a physical examination that reveals no clinically significant abnormalities other than those expected for subjects with acute infectious diarrhea. Exclusion Criteria: Non breast-fed children (group I and group II): Children of either sex who are fully or partially breast-fed until one week before enrolment (since breastfed children receive naturally HMO, their inclusion into the ORS/zinc or HMO/ORS/zinc arms would critically interfere with the study question; depending on children's age 30 to 50 % of mothers would do so at icddr,b). However, an unblinded reference group will be constituted by age-matched children who are breastfed at the moment of hospitalization for acute diarrhea and where the mothers want to continue breastfeeding on the study ward (so breastfeeding is only an exclusion for the randomized groups). Suspected or confirmed cholera as detected by a positive DF examination in stool collected on admission. (The large volume and quick evacuation of stool could interfere with product presence in the gut) Symptom duration > 48 hours at screening. Vomiting severity that is likely to make administration and retention of test product impossible. Severe malnutrition defined (using z-scores) as: severe stunting (SS; height-for-age z-score < -3.00); severe underweight (SU; weight-for-age z-score < -3.00), and severe wasting (SW; weight-for-height z-score < -3.00), using the World Health Organization reference value. Moderate malnutrition was defined as follows: moderate stunting (height-for-age z-score -3.00 to < -2.00); moderate underweight (weight-for-age z-score -3.00 to < -2.00); and moderate wasting (weight-for-height z-score -3.00 to < -2.00). We considered children as well-nourished if their z-scores for weight-for-age, height-for-age and weight-for-height z-score were form -2.00 to +1.00. Children with moderate malnutrition will be enrolled since they develop with higher frequency PD). Child already receiving antibiotics or anti-motility drugs for this diarrhea episode prior to screening. Children with any food allergy. Breast-fed children, (Group III - Reference group) Exclusive Breastfed children Either sex: Male and female Age 6-12 month Acute diarrhoea (<48 hours) without interfering co-morbidities, e.g. acute respiratory tract infection, sepsis, gross electrolyte imbalances etc. Written informed consent must be obtained prior to admission to this study. The subject has a physical examination that reveals no clinically significant abnormalities other than those expected for subjects with acute infectious diarrhea.

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 2 Years

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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ORS+ZINC<br>Oral rehydration solution + Zinc | Other: Oral rehydration solution<br> <br> * Other names: ORS;Other: Zinc<br> <br> |
| Experimental: ORS+ZINC+HMO<br>Oral rehydration solution + Zinc + Human milk oligosaccharides | Other: Oral rehydration solution<br> <br> * Other names: ORS;Other: Zinc<br> <br> Other: Human milk oligosaccharides<br> <br> * Other names: HMO;|
| Placebo Comparator: ORS+ZINC+Breastfeeding<br>Oral rehydration solution + Zinc + Breastfeeding | Other: Oral rehydration solution<br> <br> * Other names: ORS;Other: Zinc<br> <br> Other: Breastfeeding<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement (change) of clinical symptoms of diarrhea | Passage of the last abnormal stool prior to formed/ soft stools during two consecutive 8-hour periods. | Day1, Day2, Day3, Day4, Day5, Day6, Day7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stools output | Stools output, expressed as g/kg of body weight (cumulative output) | Day1, Day2, Day3, Day4, Day5, Day6, Day7 | 
| Weight gain |  | Day1, Day2, Day3, Day4, Day5, Day6, Day7, Day14 | 
| Adverse events |  | Day1, Day2, Day3, Day4, Day5, Day6, Day7, Day14 | 
| Daily stool frequency |  | Day1, Day2, Day3, Day4, Day5, Day6, Day7 | 
| The number of vomiting |  | Day1, Day2, Day3, Day4, Day5, Day6, Day7 | 
| The duration of vomiting |  | Day1, Day2, Day3, Day4, Day5, Day6, Day7 | 
| Change in Z-score |  | Day1, Day14 | 
| The amount of ORS to correct dehydration expressed as ml ORS /kg body weight, daily and cumulative input |  | Day1, Day2, Day3, Day4, Day5, Day6, Day7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Children, Diarrhea, Human milk oligosaccharides