Can Supplementation With Lactobacillus Reuteri and Omega-3 Fatty Acids During Pregnancy and Lactation Reduce the Risk of Allergic Disease in Infancy? (PROOM-3)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2012 by Ostergotland County Council, Sweden
Sponsor:
Information provided by (Responsible Party):
Karel Duchén, MD, Ostergotland County Council, Sweden
ClinicalTrials.gov Identifier:
NCT01542970
First received: February 27, 2012
Last updated: March 2, 2012
Last verified: March 2012
  Purpose

The incidence of allergic disease has increased worldwide during the last decades. Initially, a lot of effort has been put in elucidating which of the known risk factors commonly associated to the development of allergic disease early in life was the cause of this increase. Studies showing a reduced incidence of allergic disease in the former socialist countries in comparison to countries with a "Western lifestyle" have shown that risk factors as allergen exposure, environmental pollution and tobacco exposure are also present in societies with a less affluent lifestyle. This suggests the disappearance of factor protecting against the development of allergic diseases in affluent environment.The development of allergic diseases begins during the first year of life with eczema, both non-IgE- and IgE-associated, and food allergy, progressing during childhood with the development of asthma bronchiale, also both non-IgE- and IgE-associated, and later development of allergic rhinoconjunctivitis, i.e. the atopic march. The immune system of the neonate is influenced by maternal immunity, both via the placenta and breast milk. Thus, the immunological interaction between the mother and her offspring is close during pregnancy and lactation. The association of cord blood IgE levels with maternal but not paternal atopic heredity, may depend on a possibly stronger placental Th2 shift in atopic mothers. Thus, factors influencing/protecting against the development of allergic disease early in life, would be important already during pregnancy, birth and early postnatal life. Two major hypotheses have been assessed during the last decade: Proper microbial stimulation, including the establishment of the gut flora in infancy and the relationship between low omega 3-polyunsaturated fatty acids in the western diet and the incidence of allergic disease.

This is a double blind randomized study. Families with at least one parent/sibling with clinical symptoms/history of allergic disease will be invited to participate in this study. Pregnant mothers will be included in the study at the 20th week of gestation. They will be randomized to 4 study groups, one will receive placebo capsules, the second will receive omega-3 PUFA supplementation and placebo regarding L. reuteri, the third will receive L. reuteri and placebo regarding omega-3 PUFA and the fourth group will receive both omega-3 PUFA and L. reuteri supplementation. Omega-3 supplementation will be given to mothers from pregnancy and lactation while L. reuteri will be given to the mothers during pregnancy and later to the children during the first year of life.The children will be clinically followed by an allergy nurse regularly. Questionnaires regarding data on environment, siblings, pets, breast feeding, smoking exposure, upper respiratory and other infections and clinical symptoms of allergic disease will be filled regularly. Skin prick tests (SPTs) will be performed in the children at 6 and 12 months with milk, egg, wheat, peanut and cat. At 24 months, timothy and birch allergen extracts will be added. A pediatrician will assess the children at 24 months of life and whenever it is needed during the study period. Dietary habits will be assessed during pregnancy (25th gestational week) and 6 months after child birth. Blood samples in the children will be taken from cord blood and at 6, 12 and 24 months of life. Maternal blood samples will be taken at 20th weeks of gestation and at child birth. Milk samples will be collected 1-4 days after partus and monthly during the first 4 months of lactation. Maternal gastrointestinal function will be addressed by validated diary cards. Saliva from the children and fecal samples from mother and child will also be collected according to the following protocol.


Condition Intervention
Allergy
Gastrointestinal Function
Dietary Supplement: Placebo
Dietary Supplement: Omega-3 fatty acids
Dietary Supplement: Refined coconut and peanut oil without L. reuteri
Dietary Supplement: L. reuteri

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: Combined Dietary Supplementation With Lactobacillus Reuteri and Omega-3 PUFA During Pregnancy and Postnatally in Relation to Development of IgE-associated Disease During Infancy

Resource links provided by NLM:


Further study details as provided by Ostergotland County Council, Sweden:

Primary Outcome Measures:
  • IgE associated disease [ Time Frame: 2 years of age ] [ Designated as safety issue: No ]
    A food reaction is defined as gastrointestinal symptoms, hives, aggravated eczema or wheezing following ingestion of a certain food with recovery after food elimination from the diet and reoccurrence of symptoms after ingestion of the particular food. Eczema is characterized as reoccurring, itching eczematous and lichenified or nummular dermatitis. Doctor diagnosed wheezing at least three times during the first two years is required for the diagnosis of asthma. If specific positive SPT or serum IgE antibodies is present, the food reaction, eczema in defined as IgE associated.


Secondary Outcome Measures:
  • Maternal gastrointestinal function [ Time Frame: 20th gestational week to 6 months post partum ] [ Designated as safety issue: No ]
    Maternal gastrointestinal function will be addressed by validated diary cards. The mothers will record every single stool, stool consistency, and corresponding defecatory symptoms (urgency, straining, and feeling of incomplete evacuation) for seven days at gestational week 25 and 35. Stool consistency will be defined by the Bristol Stool Form Scale. The mothers will also record every meal, and episodes (start and ending time) of abdominal pain and bloating.


Estimated Enrollment: 496
Study Start Date: February 2012
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Placebo for both L. reuteri and omega-3 fatty acids.
Dietary Supplement: Placebo
Olive oil
Dietary Supplement: Refined coconut and peanut oil without L. reuteri
2x20 drops daily to the mother from gw 20 and from birth to the child during the first year of life
Experimental: L. reuteri and placebo
Active Lactobacillus reuteri and placebo for omega-3 fatty acids
Dietary Supplement: Placebo
Olive oil
Dietary Supplement: L. reuteri
The L. reuteri supplementation comprises of L. reuteri suspension 109 colony forming units (CFU) in oil (refined coconut and peanut oil) (20 droplets x 2 daily) to the mothers during pregnancy and 108 CFU (5 droplets x 1) to the children during the first years of life
Experimental: Omega-3 fatty acids and placebo
Placebo for L. reuteri and active for omega-3 fatty acids
Dietary Supplement: Omega-3 fatty acids
Omega-3 PUFA treatment comprises of maternal supplementation of 3 capsules of Pikasol® (1g capsules containing 640 mg ω-3 PUFA) 2 times daily during pregnancy and lactation.
Dietary Supplement: Refined coconut and peanut oil without L. reuteri
2x20 drops daily to the mother from gw 20 and from birth to the child during the first year of life
Experimental: L. reuteri and omega-3 fatty acids
Active L. reuteri and active omega-3 fatty acids
Dietary Supplement: L. reuteri
The L. reuteri supplementation comprises of L. reuteri suspension 109 colony forming units (CFU) in oil (refined coconut and peanut oil) (20 droplets x 2 daily) to the mothers during pregnancy and 108 CFU (5 droplets x 1) to the children during the first years of life

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • pregnant women expecting a child with at least one parent or a sibling with clinical symptoms/history of allergic disease
  • breastfeeding for at least 3 months is mandatory for inclusion in the statistical assessment in the study

Exclusion Criteria:

  • mothers with fish allergy
  • twin pregnancy
  • mothers previously/currently using omega-3 PUFA or probiotic dietary supplementation
  • children born before gestational week 33 or seriously ill will be excluded from the study.
  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: NCT01542970

Contacts
Contact: Karel M Duchén, MD, PhD +46-10-103 1355 Karel.Duchen.Munoz@lio.se

Locations
Sweden
Allergicentrum, Universitetssjukhuset Recruiting
Linköping, Sweden, 58185
Sponsors and Collaborators
Ostergotland County Council, Sweden
Investigators
Principal Investigator: Karel M Duchén, MD, PhD Östergötland county council
Principal Investigator: Maria C Jenmalm, PhD Linkoeping University
  More Information

No publications provided

Responsible Party: Karel Duchén, MD, MD, Ostergotland County Council, Sweden
ClinicalTrials.gov Identifier: NCT01542970     History of Changes
Other Study ID Numbers: FaLr-013
Study First Received: February 27, 2012
Last Updated: March 2, 2012
Health Authority: Sweden: Regional Ethical Review Board

Keywords provided by Ostergotland County Council, Sweden:
intervention
lactobacillus reuteri
omega-3 fatty acids
pregnancy
lactation
allergic symptoms
IgE associated disease
gastrointestinal function

ClinicalTrials.gov processed this record on September 11, 2014