Use of a Probiotic Supplement to Prevent Asthma in Infants

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2013 by University of California, San Francisco
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT00113659
First received: June 9, 2005
Last updated: June 11, 2013
Last verified: June 2013

June 9, 2005
June 11, 2013
June 2005
May 2014   (final data collection date for primary outcome measure)
Development of atopic dermatitis [ Time Frame: Measured from birth to 3 years of age ] [ Designated as safety issue: No ]
Not Provided
Complete list of historical versions of study NCT00113659 on ClinicalTrials.gov Archive Site
Early clinical markers of asthma, including frequent wheezing, wheezing without upper or lower respiratory tract infections, allergic rhinitis, atopic dermatitis, serum IgE, and eosinophilia [ Time Frame: Measured from birth to 3 years of age ] [ Designated as safety issue: No ]
Not Provided
Not Provided
Not Provided
 
Use of a Probiotic Supplement to Prevent Asthma in Infants
Trial of Infant Probiotic Supplementation to Prevent Asthma

The goal of the study is to understand the mechanisms of how antigen presentation affects the developing immune system and subsequently affects susceptibility to, or protects against, asthma development. This randomized controlled study will test the effectiveness of daily supplementation of Lactobacillus GG for the first 6 months of life on the early immunological development of asthma.

BACKGROUND:

During infancy, environmental factors may affect immune system development and lead to the development of asthma. The hygiene hypothesis suggests that the absence of endotoxin exposure leads to an unfavorable Th1/Th2 balance. Thus, a controlled antigen exposure during infancy may establish a Th1/Th2 balance that blocks the onset of asthma or slows the progression of the disease.

Lactobacillus is a bacterium commonly found in many foods (e.g., yogurt) in the typical childhood diet. It is also used as a probiotic supplement to prevent the development of diarrhea. Due to its safety and availability, Lactobacillus is an ideal bacterium to use as an antigen exposure to test the hygiene hypothesis.

Consistent with the hygiene hypothesis, observational studies suggest that early Lactobacillus exposure leads to decreased risk of developing atopic dermatitis, which has been associated with asthma in later years. The investigators are aware of no study that has examined the effect of Lactobacillus on the development of early markers of asthma in children at risk for developing the disease. They hypothesize that Lactobacillus can be used as an antigen exposure to establish a Th1/Th2 balance that blocks the development of early markers of asthma.

DESIGN NARRATIVE:

The hygiene hypothesis suggests that the absence of endotoxin exposure leads to an unfavorable Th1/Th2 balance. A controlled antigen exposure during infancy may help establish a Th1/ Th2 balance that blocks the onset or progression of asthma. Lactobacillus is a bacterium found in many foods in the typical pediatric diet, and is used as a supplement to prevent diarrhea. Due to the safety, feasibility, and early promising results in preventing atopic dermatitis, Lactobacillus is an ideal bacterium to use as an exposure to test the hygiene hypothesis. The investigators hypothesize that such an exposure may block or delay development of early markers of asthma.

The study will use a randomized placebo-controlled trial design to measure the effect of a 6-month daily exposure of Lactobacillus, as an infant supplement, on immune system and asthma development during the first 3 years of life.

The study will measure the effect of the antigen exposure on the presence and time to presentation of: (1) early clinical markers for asthma development (frequent wheezing, wheezing without colds, rhinitis, and atopic dermatitis); (2) early immunologic markers for asthma development (eosinophilia, immunoglobulin E); and (3) development of a T-helper phenotype (Th-1 vs Th-2). Investigators will characterize the Th phenotype by measuring the whole blood lymphocyte response to stimulants, focusing on Th1 (IFN-gamma, interleukin (IL)-12) and Th2 cytokines (IL-10, IL-4, IL-13), as well as real-time reverse transcriptase polymerase chain reaction (RT-PCR) with PCR amplification (TaqMan) to quantify RNA transcripts. Clinical and immunologic markers will be measured up to 3 years of age.

Adherence will be assessed using diaries, pill count, and Lactobacillus stool cultures.

The study will use intention-to-treat analysis and will control for the impact of family, environmental, diet, and demographic factors on outcomes using multivariate regression and survival analysis techniques. Investigators expect that when compared to controls, subjects receiving Lactobacillus will have decreased and delayed development of markers for asthma, and a greater likelihood of developing a Th1 phenotype.

Interventional
Not Provided
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Asthma
  • Dietary Supplement: Probiotic
    Daily dose of ten to the tenth colony-forming units of Lactobacillus GG and 225 mg of inulin for the first 6 months of life.
    Other Name: Culturelle
  • Dietary Supplement: Placebo
    Daily dose of placebo supplement containing 325mg inulin for the first 6 month of life.
  • Active Comparator: 1
    Participants in this arm will receive Lactobacillus GG.
    Intervention: Dietary Supplement: Probiotic
  • Placebo Comparator: 2
    Participants in this arm will receive a placebo.
    Intervention: Dietary Supplement: Placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
276
January 2015
May 2014   (final data collection date for primary outcome measure)

Inclusion criteria:

  • Expectant parents either of whom have a history of asthma
  • Parents willing to add a probiotic supplement or placebo to one feeding each day for 6 months

Exclusion criteria:

  • A sibling currently or previously enrolled in the study
  • Any major congenital birth deformities, acute illness at enrollment, or chronic conditions affecting food intake or metabolism
  • Participation in another clinical study
  • Infants from multiple gestation births (since only one child per family will be included in the study, incorporating a child from a multiple birth would add unnecessary burden to parents by requiring them to administer different formulas to different children)
Both
up to 4 Days
Yes
Contact: Michael D. Cabana, MD, MPH 415-476-5473 Michael.Cabana@ucsf.edu
Contact: Michelle L. McKean, MPH, RD 415-476-2860 McKeanm@peds.ucsf.edu
United States
 
NCT00113659
187, R01HL080074, R01 HL080074
Yes
University of California, San Francisco
University of California, San Francisco
National Heart, Lung, and Blood Institute (NHLBI)
Principal Investigator: Michael D. Cabana, MD, MPH University of California, San Francisco
University of California, San Francisco
June 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP