Brief Summary
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.
Brief Title
Use of a Probiotic Supplement to Prevent Asthma in Infants
Detailed Description
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.
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.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Asthma
Eligibility Criteria
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)
* 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)
Inclusion Criteria
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
* 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
Gender
All
Gender Based
false
Keywords
Asthma
Probiotics
Prevention
Eczema
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
4 Days
Minimum Age
1 Day
NCT Id
NCT00113659
Org Class
Other
Org Full Name
Montefiore Medical Center
Org Study Id
2019-10582
Overall Status
Completed
Phases
Not Applicable
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
Trial of Infant Probiotic Supplementation to Prevent Asthma
Primary Outcomes
Outcome Measure
Development of atopic dermatitis
Outcome Time Frame
Measured from birth to 3 years of age
Secondary Ids
Secondary Id
R01HL080074
Secondary Outcomes
Outcome Time Frame
Measured from birth to 3 years of age
Outcome Measure
Early clinical markers of asthma, including frequent wheezing, wheezing without upper or lower respiratory tract infections, allergic rhinitis, atopic dermatitis, serum IgE, and eosinophilia
Start Date
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Child
Locked Fields
Render the field
Maximum Age Number (converted to Years and rounded down)
0
Minimum Age Number (converted to Years and rounded down)
0
Investigators
Investigator Type
Principal Investigator
Investigator Name
Michael Cabana
Investigator Email
mcabana@montefiore.org