NCT01285830

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
232

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Feb 2001

Longer than P75 for phase_2

Geographic Reach
1 country

3 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 1, 2001

Completed
9.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2010

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2010

Completed
9 months until next milestone

First Submitted

Initial submission to the registry

January 27, 2011

Completed
1 day until next milestone

First Posted

Study publicly available on registry

January 28, 2011

Completed
Last Updated

March 20, 2014

Status Verified

January 1, 2011

Enrollment Period

9.2 years

First QC Date

January 27, 2011

Last Update Submit

March 19, 2014

Conditions

Allergic Conditions

Keywords

InfantsProbioticsPreventionLactobacillus reuteriEczemaIgESensitizationMicrobiotaChemokines

Outcome Measures

Primary Outcomes (1)

  • Allergic disease

    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 Outcomes (8)

  • Sensitization

    incidence until 2 years of age

  • IgE-associated allergic disease

    Incidence until 2 years of age

  • Lactobacillus reuteri colonization in stool and breast milk

    Point prevalance until 2 years of age

  • Cytokines in breast milk

    1-3 days and 1 months postpartum

  • Th1 and Th2- associated chemokines in blood samples

    Development from birth until 2 years of age

  • +3 more secondary outcomes

Study Arms (2)

Placebo

PLACEBO COMPARATOR
Dietary Supplement: Placebo

Lactobacillus reuteri

ACTIVE COMPARATOR
Dietary Supplement: Lactobacillus reuteri

Interventions

Lactobacillus reuteriDIETARY_SUPPLEMENT

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)

Lactobacillus reuteri
PlaceboDIETARY_SUPPLEMENT

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

Placebo

Eligibility Criteria

Sexall
Healthy VolunteersYes
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Pediatric Clinic, Ryhov Hospital

Jönköping, Sweden

Location

Pediatric Clinic, University Hospital

Linköping, SE 581 85, Sweden

Location

Pediatric Clinic, Vrinnevi Hospital

Norrköping, Sweden

Location

Related Publications (12)

  • Abrahamsson TR, Jakobsson T, Bottcher MF, Fredrikson M, Jenmalm MC, Bjorksten B, Oldaeus G. Probiotics in prevention of IgE-associated eczema: a double-blind, randomized, placebo-controlled trial. J Allergy Clin Immunol. 2007 May;119(5):1174-80. doi: 10.1016/j.jaci.2007.01.007. Epub 2007 Mar 8.

    PMID: 17349686RESULT

  • Bottcher MF, Abrahamsson TR, Fredriksson M, Jakobsson T, Bjorksten B. Low breast milk TGF-beta2 is induced by Lactobacillus reuteri supplementation and associates with reduced risk of sensitization during infancy. Pediatr Allergy Immunol. 2008 Sep;19(6):497-504. doi: 10.1111/j.1399-3038.2007.00687.x. Epub 2008 Jan 22.

    PMID: 18221472RESULT

  • Abrahamsson TR, Sinkiewicz G, Jakobsson T, Fredrikson M, Bjorksten B. Probiotic lactobacilli in breast milk and infant stool in relation to oral intake during the first year of life. J Pediatr Gastroenterol Nutr. 2009 Sep;49(3):349-54. doi: 10.1097/MPG.0b013e31818f091b.

    PMID: 19525871RESULT

  • Connolly E, Abrahamsson T, Bjorksten B. Safety of D(-)-lactic acid producing bacteria in the human infant. J Pediatr Gastroenterol Nutr. 2005 Oct;41(4):489-92. doi: 10.1097/01.mpg.0000176179.81638.45. No abstract available.

    PMID: 16205524RESULT

  • Abrahamsson TR, Sandberg Abelius M, Forsberg A, Bjorksten B, Jenmalm MC. A Th1/Th2-associated chemokine imbalance during infancy in children developing eczema, wheeze and sensitization. Clin Exp Allergy. 2011 Dec;41(12):1729-39. doi: 10.1111/j.1365-2222.2011.03827.x. Epub 2011 Aug 1.

    PMID: 21801246RESULT

  • Abrahamsson TR, Jakobsson HE, Andersson AF, Bjorksten B, Engstrand L, Jenmalm MC. Low diversity of the gut microbiota in infants with atopic eczema. J Allergy Clin Immunol. 2012 Feb;129(2):434-40, 440.e1-2. doi: 10.1016/j.jaci.2011.10.025. Epub 2011 Dec 6.

    PMID: 22153774RESULT

  • Forsberg A, Abrahamsson TR, Bjorksten B, Jenmalm MC. Pre- and post-natal Lactobacillus reuteri supplementation decreases allergen responsiveness in infancy. Clin Exp Allergy. 2013 Apr;43(4):434-42. doi: 10.1111/cea.12082.

    PMID: 23517039RESULT

  • Jakobsson HE, Abrahamsson TR, Jenmalm MC, Harris K, Quince C, Jernberg C, Bjorksten B, Engstrand L, Andersson AF. Decreased gut microbiota diversity, delayed Bacteroidetes colonisation and reduced Th1 responses in infants delivered by caesarean section. Gut. 2014 Apr;63(4):559-66. doi: 10.1136/gutjnl-2012-303249. Epub 2013 Aug 7.

    PMID: 23926244RESULT

  • Abrahamsson TR, Jakobsson T, Bjorksten B, Oldaeus G, Jenmalm MC. No effect of probiotics on respiratory allergies: a seven-year follow-up of a randomized controlled trial in infancy. Pediatr Allergy Immunol. 2013 Sep;24(6):556-61. doi: 10.1111/pai.12104. Epub 2013 Jul 31.

    PMID: 23902407RESULT

  • Abrahamsson TR, Jakobsson HE, Andersson AF, Bjorksten B, Engstrand L, Jenmalm MC. Low gut microbiota diversity in early infancy precedes asthma at school age. Clin Exp Allergy. 2014 Jun;44(6):842-50. doi: 10.1111/cea.12253.

    PMID: 24330256RESULT

  • Forsberg A, Abrahamsson TR, Bjorksten B, Jenmalm MC. Pre- and postnatal administration of Lactobacillus reuteri decreases TLR2 responses in infants. Clin Transl Allergy. 2014 Jun 25;4:21. doi: 10.1186/2045-7022-4-21. eCollection 2014.

    PMID: 25002964DERIVED

  • Abrahamsson TR, Rautava S, Moore AM, Neu J, Sherman PM. The time for a confirmative necrotizing enterocolitis probiotics prevention trial in the extremely low birth weight infant in North America is now! J Pediatr. 2014 Aug;165(2):389-94. doi: 10.1016/j.jpeds.2014.05.012. Epub 2014 Jun 16. No abstract available.

    PMID: 24948349DERIVED

MeSH Terms

Conditions

Eczema

Condition Hierarchy (Ancestors)

DermatitisSkin DiseasesSkin and Connective Tissue DiseasesSkin Diseases, Eczematous

Study Officials

  • Bengt Björkstén, MD, PhD

    The National Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER GOV

Study Record Dates

First Submitted

January 27, 2011

First Posted

January 28, 2011

Study Start

February 1, 2001

Primary Completion

May 1, 2010

Study Completion

May 1, 2010

Last Updated

March 20, 2014

Record last verified: 2011-01

Locations

SE(3)