Clinical trial NCT04144491: Effect of L. Rhamnosus Yoba on RTI and Other Health Outcomes Among Children (3-6 Years) in Uganda
Official title: A Nutritional Trial on Effect of Probiotic Yoghurt Containing Lactobacillus Rhamnosus Yoba on Respiratory Tract Infection and Other Health Outcomes Among Children Aged 3-6 Years in Southwest Uganda
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Respiratory Tract Infections
Diarrhea
Skin Diseases
Tinea Capitis
Common Cold
Keywords: Lactobacillus rhamnosus yoba 2012
Children
Lead sponsor: VU University of Amsterdam
Sponsor class: OTHER
Collaborators: name: Yoba for Life Foundation
First posted: 2019-10-30
Enrollment: 195
Sex: ALL
Minimum age (years): 3
Maximum age (years): 7
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This is a nutritional trial with two arms: 1) Intervention arm of Probiotic Yoghurt containing Lactobacillus rhamnosus yoba 2012 and 2) Control arm of custard-like dairy product. The study subjects are 200 children between the age of 3-6 years that attend a school in Southwestern Uganda, Sheema district. Children will be randomized and enrolled in either the yoghurt (100 children) or the placebo (100 children) arm. The children will be monitored for 3 weeks in the baseline in regards to the incidence of common childhood diseases. During these three weeks, stool, saliva and urine samples will be collected. Also measurement of anthropometric indicators (weight and height) will take place. Subsequently, the children will consume either 100ml yoghurt or 100ml placebo product, once per day for five days per week for nine weeks, while being daily monitored in regards to the incidence of common childhood diseases. The same samples (stool, urine and saliva) and assessments (anthropometric) will take place at end line.

Detailed description: This is a nutritional trial with two arms: 1) Intervention arm of Probiotic Yoghurt containing Lactobacillus rhamnosus yoba 2012 and 2) Placebo arm of custard-like dairy product. The study subjects are 200 children between the age of 3-6 years that attend a school in Southwestern Uganda, Sheema district. Children will be randomized and enrolled in either the yoghurt (100 children) or the placebo (100 children) arm. The children will be monitored for 3 weeks in the baseline in regards to the incidence of common childhood diseases. During these three weeks, stool, saliva and urine samples will be collected. Also measurement of anthropometric indicators (weight and height) will take place. Subsequently, the children will consume either 100ml yoghurt or 100ml placebo product, once per day for five days per week for nine weeks, while being daily monitored in regards to the incidence of common childhood diseases. The same samples (stool, urine and saliva) and assessments (anthropometric) will take place at end line. The yoghurt and the placebo product will be locally sourced in the district where the school is located. Monitoring and data collection tools are:

1. Baseline, mid line and end line questionnaire administered to parents to identify confounding factors (e.g. use of medication and diet from home) of treatment and control group.
2. Weight and height measurements at baseline and end line in both the treatment and control group (total 2 times).
3. Daily monitoring of the incidence of RTIs, diarrhoea, skin rashes or other diseases in treatment and control groups by a nurse, registered in a mobile application.
4. Collection of urine samples every 4 weeks for 3 months (total 4 times), for assessment of impact of the intervention on system health.
5. Collection of stool samples at baseline and end line, for assessment of impact of the intervention on gut health.
6. Collection of saliva samples before and towards the end of the intervention, for assessment of impact of the intervention on immune biomarkers

The consumption of probiotic yoghurt at school as paid for by the parents, is currently being promoted by an Non-Governmental Organization (NGO) in the region. Following this program, children from a primary school that includes a pre-primary section, in which both the management and the parents have recently decided to purchase yoghurt for the pupils on regular basis will be recruited. The study subjects (children) are recruited at these institutions, after consent from the parent has been obtained. The parent is free to provide his/her child with yoghurt, even if the parent does not consent for the child to take part in the study.

The study will start three weeks before either yoghurt or placebo consumption commences, in order to establish a solid baseline. With the help of tablets and a specially designed mobile application, nurses will keep track of their pupils' health by tracking incidence of diarrhoea, respiratory tract infections, skin rashes and other diseases. Teachers will keep track of the daily attendance of pupils.

Measurements of weight and height will be measured by a nurse at baseline and end line. The measurements will be conducted with the help of Standard Operations Procedures as provided by Life Study and analyzed with the help of World Health Organization (WHO) guidelines. Urine samples will be taken from the children at baseline, after 4 weeks, after 8 weeks, and at end line (12 weeks). Stool samples and saliva samples will be taken at the beginning and the end of the study.

During these 3 months in which the children will be monitored, a questionnaire will be administered to the parents of the children at the start, middle and end of the study. The primary objective and content of the questionnaire is related to diet of the children outside school, in order to determine whether there are significant differences between the diets of the children in the treatment group and in the control group. The questionnaires will furthermore include questions about absenteeism and causes thereof, incidence of diarrhoea, Respiratory Tract Infections (RTI) or any other diseases, and the use of any type of drug or treatment, in order to verify and supplement the information provided by the class-teacher. Lastly, information on the vaccination history of the child will be obtained from the parent

Eligibility criteria: Inclusion Criteria:

* Children of a pre-primary institution in Southwest Uganda are targetted
* During interactions with the pre-primary institutions prior to the study, the parents of the children have agreed to pay for their child to either take probiotic yoghurt (100ml five times per week).
* Parents are willing to provide written consent for their child to participate in the study

Exclusion Criteria:

* The child does not comply with the inclusion criteria
* The child has an aversion against yoghurt or milk products
* The child is lactose-intolerant as indicated by the parent, or has any other medical condition that will prevent him/her from taking yoghurt or milk products

Primary outcomes:
measure: The number of children on each individual day that suffers from Respiratory Tract Infections
timeFrame: 3 months
Secondary outcomes:
measure: Changes in weight of children during the study period
timeFrame: 3 months
measure: Changes in height of the children during the study period
timeFrame: 3 months
measure: The number of children on each individual day that suffers from Diarrhea
timeFrame: 3 months
measure: The number of children on each individual day that suffers from any form of skin diseases
timeFrame: 3 months
measure: The number of children on each individual day that is absent
timeFrame: 3 months
measure: Differences in the metabolic profile of childrens urine between baseline and after 9 weeks of intervention using 1H-Nuclear Magnetic Resonance (NMR) Spectroscopy
timeFrame: 3 months
measure: Differences in the microbial profile of childrens stool between baseline and after 9 weeks of intervention using Next Generation Sequencing (NGS) in combination with Fluorescence In Situ Hybridisation hyphenated to Flow Cytometry (Flow-FISH)
timeFrame: 3 months
measure: Differences in the immune markers of childrens saliva between baseline and after 9 weeks of intervention
timeFrame: 3 months
Other outcomes:
Locations:
city: Kabwohe
country: Uganda
facility: Paragon primary and nursery School
state: Sheema
Study officials:
affiliation: VU Amsterdam
name: Remco Kort, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dezateux, C., Williams, J., Walton, S., Wells, J., 2016. Life Study Standard Operating Procedures: Adult Anthropometry.
citation: Williams, J., Walton, S., Wells, J., 2016. Life Study Standard Operating Procedures: Infant Anthropometry.
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citation: World Health Organization (Ed.), 2006. WHO child growth standards: length/height-for-age, weight-for-age, weight-for-length, weight-for-height and body mass index-for-age ; methods and development. WHO Press, Geneva.
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citation: Kort R, Westerik N, Mariela Serrano L, Douillard FP, Gottstein W, Mukisa IM, Tuijn CJ, Basten L, Hafkamp B, Meijer WC, Teusink B, de Vos WM, Reid G, Sybesma W. A novel consortium of Lactobacillus rhamnosus and Streptococcus thermophilus for increased access to functional fermented foods. Microb Cell Fact. 2015 Dec 8;14:195. doi: 10.1186/s12934-015-0370-x.
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