Clinical trial NCT02896465: Human Milk Oligosaccharides and Childhood Diarrhoea
Official title: Treatment of Acute Childhood Diarrhoea With Human Milk Oligosaccharides and Impact on Gut Micro Biota Dysbiosis and Nutritional Status
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Acute Diarrhea
Keywords: Children
Diarrhea
Human milk oligosaccharides
Lead sponsor: Société des Produits Nestlé (SPN)
Sponsor class: INDUSTRY
First posted: 2016-09-12
Enrollment: 435
Sex: ALL
Minimum age (years): 6
Maximum age (years): 2
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Improvement (change) of clinical symptoms of diarrhea
timeFrame: Day1, Day2, Day3, Day4, Day5, Day6, Day7
Secondary outcomes:
measure: Stools output
timeFrame: Day1, Day2, Day3, Day4, Day5, Day6, Day7
measure: Weight gain
timeFrame: Day1, Day2, Day3, Day4, Day5, Day6, Day7, Day14
measure: Adverse events
timeFrame: Day1, Day2, Day3, Day4, Day5, Day6, Day7, Day14
measure: Daily stool frequency
timeFrame: Day1, Day2, Day3, Day4, Day5, Day6, Day7
measure: The number of vomiting
timeFrame: Day1, Day2, Day3, Day4, Day5, Day6, Day7
measure: The duration of vomiting
timeFrame: Day1, Day2, Day3, Day4, Day5, Day6, Day7
measure: Change in Z-score
timeFrame: Day1, Day14
measure: The amount of ORS to correct dehydration expressed as ml ORS /kg body weight, daily and cumulative input
timeFrame: Day1, Day2, Day3, Day4, Day5, Day6, Day7
Other outcomes:
Locations:
city: Dhaka
country: Bangladesh
facility: International Center for Diarrheal Disease Research
Study officials:
References: