Primary Prevention of Allergic Disease in Early Child by Lactobacillus Reuteri

Allergic Conditions Clinical Trial

Official title:

Primary Prevention of Allergic Disease in Early Child by Lactobacillus Reuteri

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01285830
• Other study ID #: BGB 99/02
• Secondary ID: F2000-106
• Status: Completed
• Phase: Phase 2
• First received: January 27, 2011
• Last updated: March 19, 2014
• Start date: February 2001
• Est. completion date: May 2010

Study information

• Verified date: January 2011
• Source: Linkoeping University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 232
• Est. completion date: May 2010
• Est. primary completion date: May 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Allergic Conditions

Intervention

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)
• 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

Locations

Country	Name	City	State
Sweden	Pediatric Clinic, Ryhov Hospital	Jönköping
Sweden	Pediatric Clinic, University Hospital	Linköping
Sweden	Pediatric Clinic, Vrinnevi Hospital	Norrköping

Sponsors (8)

Lead Sponsor	Collaborator
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

Country where clinical trial is conducted

Sweden, 

References & Publications (10)

Abrahamsson TR, Jakobsson HE, Andersson AF, Björkstén 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 — View Citation

Abrahamsson TR, Jakobsson HE, Andersson AF, Björkstén 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. — View Citation

Abrahamsson TR, Jakobsson T, Björkstén 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. — View Citation

Abrahamsson TR, Jakobsson T, Böttcher MF, Fredrikson M, Jenmalm MC, Björkstén 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. Epub 2007 — View Citation

Abrahamsson TR, Sandberg Abelius M, Forsberg A, Björkstén 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.1365-2222.2 — View Citation

Abrahamsson TR, Sinkiewicz G, Jakobsson T, Fredrikson M, Björkstén 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.0b — View Citation

Böttcher MF, Abrahamsson TR, Fredriksson M, Jakobsson T, Björkstén 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):4 — View Citation

Connolly E, Abrahamsson T, Björkstén B. Safety of D(-)-lactic acid producing bacteria in the human infant. J Pediatr Gastroenterol Nutr. 2005 Oct;41(4):489-92. — View Citation

Forsberg A, Abrahamsson TR, Björkstén 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. — View Citation

Jakobsson HE, Abrahamsson TR, Jenmalm MC, Harris K, Quince C, Jernberg C, Björkstén B, Engstrand L, Andersson AF. Decreased gut microbiota diversity, delayed Bacteroidetes colonisation and reduced Th1 responses in infants delivered by caesarean section. G — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Sensitization	Positive skin prick test and /or circulation IgE against allergen in blood	incidence until 2 years of age
Secondary	IgE-associated allergic disease	Allergic disease was classified as IgE-associated if the symptomatic infant also was sensitized	Incidence until 2 years of age
Secondary	Lactobacillus reuteri colonization in stool and breast milk	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
Secondary	Cytokines in breast milk	Cytokines in breast milk from the mother will be measured by ELISA.	1-3 days and 1 months postpartum
Secondary	Th1 and Th2- associated chemokines in blood samples	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
Secondary	Microbial composition in stool samples	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
Secondary	Allergic disease at 7 years of age	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
Secondary	Prevalence of caries in primary dentition at 8 years of age	Prevalence of caries in primary dentition is examined by dentists at 8 yeas of age. These diagnosis are based on predefined criteria.	2009-2012