Primary Prevention of Allergic Disease in Early Child by Lactobacillus Reuteri

This study has been completed.
Sponsor:
Collaborators:
BioGaia AB, Sweden
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
The Swedish Research Council
University Hospital, Linkoeping
Information provided by:
Linkoeping University
ClinicalTrials.gov Identifier:
NCT01285830
First received: January 27, 2011
Last updated: March 19, 2014
Last verified: January 2011
  Purpose

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.


Condition Intervention Phase
Allergic Conditions
Dietary Supplement: Lactobacillus reuteri
Dietary Supplement: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Primary Prevention of Allergic Disease in Early Child by Lactobacillus Reuteri

Resource links provided by NLM:


Further study details as provided by Linkoeping University:

Primary Outcome Measures:
  • Allergic disease [ Time Frame: Incidence until 2 years of age ] [ Designated as safety issue: No ]
    Allergic disease was defined as any of the following: eczema, asthma, allergic rhinoconjunctivitis, allergic urticaria, gastrointestinal allergy. These diagnosis are based on predefined criteria.


Secondary Outcome Measures:
  • Sensitization [ Time Frame: incidence until 2 years of age ] [ Designated as safety issue: No ]
    Positive skin prick test and /or circulation IgE against allergen in blood

  • IgE-associated allergic disease [ Time Frame: Incidence until 2 years of age ] [ Designated as safety issue: No ]
    Allergic disease was classified as IgE-associated if the symptomatic infant also was sensitized

  • Lactobacillus reuteri colonization in stool and breast milk [ Time Frame: Point prevalance until 2 years of age ] [ Designated as safety issue: No ]
    Isolation of Lactobacillus reuteri in stool and breast milk samples from the mother and infant with conventional and molecular methods.

  • Cytokines in breast milk [ Time Frame: 1-3 days and 1 months postpartum ] [ Designated as safety issue: No ]
    Cytokines in breast milk from the mother will be measured by ELISA.

  • Th1 and Th2- associated chemokines in blood samples [ Time Frame: Development from birth until 2 years of age ] [ Designated as safety issue: No ]
    Th1 and Th2- associated chemokines will be analyzed in blood samples from the infant with ELISA and Luminex.

  • Microbial composition in stool samples [ Time Frame: Development from birth until 2 years of age ] [ Designated as safety issue: No ]
    The microbial composition in stoll samples from the mothers and infants will be assessed with conventional cultivation and molecular microbiology methods

  • Allergic disease at 7 years of age [ Time Frame: 2001-2011 ] [ Designated as safety issue: Yes ]
    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.

  • 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.


Enrollment: 232
Study Start Date: February 2001
Study Completion Date: May 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)

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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01285830

Locations
Sweden
Pediatric Clinic, Ryhov Hospital
Jönköping, Sweden
Pediatric Clinic, University Hospital
Linköping, Sweden, SE 581 85
Pediatric Clinic, Vrinnevi Hospital
Norrköping, Sweden
Sponsors and Collaborators
Linkoeping University
BioGaia AB, Sweden
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
The Swedish Research Council
University Hospital, Linkoeping
Investigators
Principal Investigator: Bengt Björkstén, MD, PhD The National Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
  More Information

Publications:

Responsible Party: Professor Bengt Björkstén, The National Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
ClinicalTrials.gov Identifier: NCT01285830     History of Changes
Other Study ID Numbers: BGB 99/02, F2000-106
Study First Received: January 27, 2011
Last Updated: March 19, 2014
Health Authority: Sweden: National Food Administration

Keywords provided by Linkoeping University:
Infants
Probiotics
Prevention
Lactobacillus reuteri
Eczema
IgE
Sensitization
Microbiota
Chemokines

ClinicalTrials.gov processed this record on August 25, 2014