Primary Prevention of Allergic Disease in Early Child by Lactobacillus Reuteri

March 19, 2014 updated by: Linkoeping University

An altered microbial exposure may be partly responsible for the increase of allergic diseases in populations with a western lifestyle. Activation of the immune system by microbes early in life is probably required for an accurate maturation of the immune system. Probiotics, live bacteria which are considered to confer health when ingested, have been suggested to prevent eczema and sensitisation infants.

The aim of this study is to assess the effect of oral supplementation with the probiotic bacterium Lactobacillus reuteri in infancy on the development of allergic disease and sensitisation during the first 2 years of life and to examine mechanisms possibly underlying eventual effects on allergic manifestations.

A follow up was performed at 7 years of age.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

An altered microbial exposure may be partly responsible for the increase of allergic diseases in populations with a western lifestyle. Activation of the immune system by microbes early in life is probably required for an accurate maturation of the immune system. Probiotics, live bacteria which are considered to confer health when ingested, have been suggested to prevent eczema and sensitisation infants.

The aim of this study is to assess the effect of oral supplementation with the probiotic bacterium Lactobacillus reuteri (L. reuteri) in infancy on the development of allergic disease and sensitisation during the first 2 years of life and to examine mechanisms possibly underlying eventual effects on allergic manifestations. In the study the development of allergic disease will also be related prospectively to immunological, nutritional and environmental factors.

The study is a prospective double-blind placebo-controlled multicenter trial, comprising 232 families with allergic disease. The families are recruited at the antenatal clinic, and the mothers will receive L. reuteri ATCC 55730 (1 x 100 000 000 colony forming units, Biogaia AB, Stockholm, Sweden) or placebo daily from gestational week 36 until delivery. Their babies then will continue with the same study product from birth until 12 months of age and will be followed up for another year. Clinical follow-up will be done at 1, 3, 6,12 and 24 months of age and telephone interviews at 2,4,5, 8, 10 and 18 months. A questionnaire will be completed on each occasion. Skin prick test will be performed at 6, 12 and 24 months of age. Venous blood will be collected from the umbilical cord and at 6, 12 and 24 months and stored as heparinized plasma or serum until assessment. Peripheral mononuclear blood cells (PBMC) will be separated from the plasma samples before storage. Blood samples will also be collected from the mother and father once during the study. The stool sample will be collected from the mother during the 1 week after delivery and the infant at 5-7 days, 1 month, 3 months, 6 months, 12 months and 24 months of age. Saliva samples will be collected at 3, 6, 12 and 24 months of age and breast milk samples will be collected from the mother 1-3 days and 1 months after delivery. The saliva, breast milk and plasma/serum samples will be stored in -20°C and stool samples and the PBMC in -70°C until assessment.

A follow up was performed at 7 years of age focusing on allergic disease. Spirometry, skin prick test was performed. Of the 188 completing the 2 year follow up, 184 also completed the 7 year follow up.

Study Type

Interventional

Enrollment (Actual)

232

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Sweden
      • Jönköping, Sweden
        • Pediatric Clinic, Ryhov Hospital
      • Linköping, Sweden, SE 581 85
        • Pediatric Clinic, University Hospital
      • Norrköping, Sweden
        • Pediatric Clinic, Vrinnevi Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Pregnant women with history of previous or present allergic disease in at least one member of the immediate family (parents or siblings).
  • Expected compliance.
  • Written informed consent obtained from parents.

Exclusion Criteria:

  • Insufficient compliance, i.e. a consumption of the study product below half of the expected.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Dietary supplement: Placebo
The placebo consists of the same oil that the active study product but without any bacteria and is not possible to differentiate from the active product by smell, taste or visual appearance
Active Comparator: Lactobacillus reuteri
Dietary supplement: Lactobacillus reuteri
The mothers started taking Lactobacillus reuteri ATCC 55730 (BioGaia AB, Stockholm, Sweden) or placebo four weeks before term and continued to do so daily until delivery. After birth, the baby commenced with the same study product as the mother at 1-3 days of age and continued daily for one year. The daily intake, five oil droplets, corresponded to 1 x 100 000 000 colony forming units (CFU)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Allergic disease
Time Frame: Incidence until 2 years of age
Allergic disease was defined as any of the following: eczema, asthma, allergic rhinoconjunctivitis, allergic urticaria, gastrointestinal allergy. These diagnosis are based on predefined criteria.
Incidence until 2 years of age

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sensitization
Time Frame: incidence until 2 years of age
Positive skin prick test and /or circulation IgE against allergen in blood
incidence until 2 years of age
IgE-associated allergic disease
Time Frame: Incidence until 2 years of age
Allergic disease was classified as IgE-associated if the symptomatic infant also was sensitized
Incidence until 2 years of age
Lactobacillus reuteri colonization in stool and breast milk
Time Frame: Point prevalance until 2 years of age
Isolation of Lactobacillus reuteri in stool and breast milk samples from the mother and infant with conventional and molecular methods.
Point prevalance until 2 years of age
Cytokines in breast milk
Time Frame: 1-3 days and 1 months postpartum
Cytokines in breast milk from the mother will be measured by ELISA.
1-3 days and 1 months postpartum
Th1 and Th2- associated chemokines in blood samples
Time Frame: Development from birth until 2 years of age
Th1 and Th2- associated chemokines will be analyzed in blood samples from the infant with ELISA and Luminex.
Development from birth until 2 years of age
Microbial composition in stool samples
Time Frame: Development from birth until 2 years of age
The microbial composition in stoll samples from the mothers and infants will be assessed with conventional cultivation and molecular microbiology methods
Development from birth until 2 years of age
Allergic disease at 7 years of age
Time Frame: 2001-2011
Allergic disease at 7 years of age was defined as any of the following: eczema, asthma, allergic rhinoconjunctivitis, allergic urticaria. These diagnosis are based on predefined criteria.
2001-2011
Prevalence of caries in primary dentition at 8 years of age
Time Frame: 2009-2012
Prevalence of caries in primary dentition is examined by dentists at 8 yeas of age. These diagnosis are based on predefined criteria.
2009-2012

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Linkoeping University

Collaborators

The Swedish Research Council
University Hospital, Linkoeping
BioGaia AB
The Ekhaga Foundation, Sweden
The Heart and Lung foundation, Sweden
The Research Council for the South-East Sweden
The Swedish Asthma and Allergy Association, Sweden

Investigators

  • Principal Investigator: Bengt Björkstén, MD, PhD, The National Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2001

Primary Completion (Actual)

May 1, 2010

Study Completion (Actual)

May 1, 2010

Study Registration Dates

First Submitted

January 27, 2011

First Submitted That Met QC Criteria

January 27, 2011

First Posted (Estimate)

January 28, 2011

Study Record Updates

Last Update Posted (Estimate)

March 20, 2014

Last Update Submitted That Met QC Criteria

March 19, 2014

Last Verified

January 1, 2011

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • BGB 99/02
  • F2000-106 (Other Grant/Funding Number: Research Council for the South-East Sweden)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Allergic Conditions

Clinical Trials on Placebo

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Bosnia & Herzegovina

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe