Human Milk Oligosaccharides and Childhood Diarrhoea

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

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.

Study Overview

• Status: Completed
• Conditions: Acute Diarrhea
• Intervention / Treatment: Other: Oral rehydration solution; Other: Zinc; Other: Human milk oligosaccharides; Other: Breastfeeding

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 435
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Bangladesh
  • Dhaka, Bangladesh
    • International Center for Diarrheal Disease Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 2 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria: Non breast-fed children (group I and group II):

1. Both male and female children between the ages of 6 months to 2 years.
2. Acute diarrhoea (<48 hours) without interfering co-morbidities, e.g. acute respiratory tract infection, sepsis, gross electrolyte imbalances etc.
3. 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.
4. Written informed consent must be obtained prior to admission to this study.
5. 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):

1. 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).
2. 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)
3. Symptom duration > 48 hours at screening.
4. Vomiting severity that is likely to make administration and retention of test product impossible.

5. 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).

6. Child already receiving antibiotics or anti-motility drugs for this diarrhea episode prior to screening.
7. Children with any food allergy.

Breast-fed children, (Group III - Reference group)

1. Exclusive Breastfed children Either sex: Male and female
2. Age 6-12 month
3. Acute diarrhoea (<48 hours) without interfering co-morbidities, e.g. acute respiratory tract infection, sepsis, gross electrolyte imbalances etc.
4. Written informed consent must be obtained prior to admission to this study.
5. The subject has a physical examination that reveals no clinically significant abnormalities other than those expected for subjects with acute infectious diarrhea.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: ORS+ZINC; Oral rehydration solution + Zinc	Other: Oral rehydration solution; Other Names: ORS; Other: Zinc
Experimental: ORS+ZINC+HMO; Oral rehydration solution + Zinc + Human milk oligosaccharides	Other: Oral rehydration solution; Other Names: ORS; Other: Zinc; Other: Human milk oligosaccharides; Other Names: HMO
Placebo Comparator: ORS+ZINC+Breastfeeding; Oral rehydration solution + Zinc + Breastfeeding	Other: Oral rehydration solution; Other Names: ORS; Other: Zinc; Other: Breastfeeding

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Nestlé

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2016
• Primary Completion (Actual): October 1, 2018
• Study Completion (Actual): February 1, 2019

Study Registration Dates

• First Submitted: August 10, 2016
• First Submitted That Met QC Criteria: September 6, 2016
• First Posted (Estimate): September 12, 2016

Study Record Updates

• Last Update Posted (Actual): July 23, 2019
• Last Update Submitted That Met QC Criteria: July 22, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Diarrhea; Children; Human milk oligosaccharides
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Diarrhea
• Other Study ID Numbers: 13.26.INF

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No