Effect of Probiotics in Reducing Infections and Allergies in Young Children Starting Daycare (ProbiComp)

The aim of the intervention is to examine the effect of a combination of the two bacterial strains BB-12 and LGG, provided for 6 month, on the prevalence of infections and allergic manifestations in small children, and how a combination of BB-12 and LGG affects the immune system, gastrointestinal tract and the microbiota. Children are enrolled during 2 winter seasons.

Study Overview

• Status: Completed
• Conditions: Respiratory Tract Infections; Allergy; Gastrointestinal Infections; Days Absent From Daycare
• Intervention / Treatment: Dietary supplement: Probiotic (2 * 10^9 cfu/day); Dietary supplement: Placebo

• Study Type: Interventional
• Enrollment (Actual): 290
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Frederiksberg, Denmark, 1958
    • Section of Paediatric and International nutrition, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 months to 1 year (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Expected to start daycare between the age of 8-14 month
• Intervention start 0 days to 12 weeks before starting daycare
• Expected to start daycare from september to february (both month included)
• Single born

Exclusion Criteria:

• Exclusion Criteria:
• Children born before 37th gestational week
• Children with a birth weight < 2500 g
• Children suffering from severe chronic illness
• Children receiving regular medication
• Children who have received antibiotics within a month before intervention start
• Children whose parents do not speak Danish

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Probiotic (2 * 10^9 cfu/d); Daily intake of bifidobacterium animalis ssp. Lactis (BB12) and Lactobacillus Rhamnosus GG (LGG) in a dosage of 10^9 cfu/day of each strain. The probiotics are provided as powder in a sachet, and can be added to food or drink	Dietary supplement: Probiotic (2 * 10^9 cfu/day); Combination of two probiotics (2 * 10^9 cfu/day) or probiotics for 6 months; Other Names: bifidobacterium animalis ssp. Lactis (BB12), 10^9 cfu/day; Lactobacillus Rhamnosus GG (LGG), 10^9 cfu/day
Placebo Comparator: Placebo; provided as powder in a sachet, and can be added to food or drink	Dietary supplement: Placebo; Placebo for 6 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of days absent from daycare due to respiratory and gastrointestinal infections	Recorded weekly by the parents using web-based questionnaires	up to 6 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute upper respiratory tract infections	Number of days with acute upper respiratory tract infections (URTI); Number of children with at least 1 episode of URTI; Number of children with at least 3 episodes of URTI; Number of URTI episodes/child/year; Duration of URTI episodes (days); Additionally,symptoms of cold (defined as 2 days with runny/stuffy nose or cough) Recorded by the parents daily/weekly using web-based questionnaires.	Up to 6 month
Acute lower respiratory infections	Number of children with at least 1 episode of a lower respiratory tract infection (LRTI). LRTI include bronchitis and pneumonia Recorded by the parents weekly using web-based questionnaires.	Up to 6 month
Gastrointestinal infections	Number of children with at least 1 episode of diarrhea; Duration of episodes with diarrhea(days); Number of episodes/child/year with diarrhea; Number of days with vomiting. Recorded by the parents daily using web-based questionnaires	Up to 6 month
Fever	Number of days with fever Recorded by the parents using web-based questionnaires	Up to 6 month
Antibiotic use	Number of treatments with antibiotics during the intervention period Recorded weekly by the parents using web-based questionnaires	Up to 6 month
Allergies	Number of children developing allergies during the intervention period (asthma, allergic rhinitis, atopic dermatitis, food allergies); Age for diagnosis of allergies; Use of medication due to allergies. Recorded by the parents using web-based questionnaires	Up to 6 month
Absence from day care due to illness other than infections	Number of days the child is absent from day care due to illness, which is not due to infections. Recorded by the parents weekly using web-based questionnaires	Up to 6 month
Parental absence from work due to illness of the child	Number of days a parent is absent from work due to illness of the child (infections and other illnesses, respectively) Recorded by the parents weekly using web-based questionnaires	Up to 6 month
Medical visits	Number of visits to a doctor due to infections and other illnesses, respectively. Recorded by the parents using web-based questionnaires	Up to 6 month
Change from baseline in Thymus size	Change in thymic size during intervention period will be evaluated using ultrasound	At baseline and after 6 mo (end of intervention)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in biological markers for the immune system	Analysis of biological material investigating the effect on the immune system by biological markers .	At baseline and after 6 mo
Change from baseline in biological markers for gastro-intestinal tract	Analysis of biological material investigating the effect on the gastrointestinal tract.	At baseline and after 6 mo
Change from baseline in Biological markers of allergy	analysis of biological samples investigating the effect on allergy by biological markers at baseline and at 6 mo	At baseline and after 6 mo

Collaborators and Investigators

• Sponsor: University of Copenhagen
• Collaborators: Odense University Hospital; University of Bergen; Chr Hansen; Statens Serum Institut; Technical University of Denmark; The Danish Council for Strategic Research

Publications and helpful links

General Publications

• Schmidt RM, Pilmann Laursen R, Bruun S, Larnkjaer A, Molgaard C, Michaelsen KF, Host A. Probiotics in late infancy reduce the incidence of eczema: A randomized controlled trial. Pediatr Allergy Immunol. 2019 May;30(3):335-340. doi: 10.1111/pai.13018. Epub 2019 Feb 21.
• Laursen MF, Laursen RP, Larnkjaer A, Michaelsen KF, Bahl MI, Licht TR. Administration of two probiotic strains during early childhood does not affect the endogenous gut microbiota composition despite probiotic proliferation. BMC Microbiol. 2017 Aug 17;17(1):175. doi: 10.1186/s12866-017-1090-7.

Study record dates

Study Major Dates

• Study Start: August 1, 2014
• Primary Completion (Actual): June 1, 2016
• Study Completion (Actual): June 1, 2016

Study Registration Dates

• First Submitted: June 30, 2014
• First Submitted That Met QC Criteria: June 30, 2014
• First Posted (Estimate): July 2, 2014

Study Record Updates

• Last Update Posted (Estimate): August 24, 2016
• Last Update Submitted That Met QC Criteria: August 23, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: Allergy; Microbiota; Infant; Infections; Immune function
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Immune System Diseases; Disease Attributes; Hypersensitivity; Infections; Communicable Diseases; Respiratory Tract Infections
• Other Study ID Numbers: H-4-2014-032 (Other Grant/Funding Number: The Danish Council for Strategic Research)