Clinical Trial: Impact of Infant Formula on Resolution of Cow's Milk Allergy

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Prospective Randomized Controlled Trial to Evaluate the Effect of Infant Formula on the Resolution of Cow's Milk Allergy of Infancy

Brief Summary:

Primary Endpoint

-The percentage of subjects who develop tolerance to cow's milk protein by 12 months post randomization to study formula.

Secondary Endpoints

  • Tolerance

    • The transcriptional profile of milk-specific T cells by clinical outcome.
    • Growth and Weight Velocity
    • Stool Consistency and Frequency
    • The estimated frequency of milk-specific T cells by clinical outcome.
    • The TCR diversity of milk-specific T cells by clinical outcome.
    • The milk allergen component-specific IgE, IgG4 and IgA by clinical outcome.

  • Safety

    • The rate of reported adverse events by treatment group.

Detailed Summary:

Cow's Milk Allergy (CMA) is prevalent and most often presents during infancy. Disease manifestations vary through a range of immediate and delayed inflammatory responses to milk protein from anaphylaxis to enterocolitis. The natural history is also highly variable; most children will achieve clinical tolerance early in life, while a minority will have disease persisting to adulthood for reasons that are not known. Most presentations are mild and are managed by restriction or reduction of immunologically intact milk protein with reintroduction sometime after a year of age; however, there are data to suggest that some level of antigenic stimulation may be beneficial. Furthermore, recent data suggest that oral probiotic exposure may also promote tolerance, though the kinetics of tolerance acquisition, the interaction between these two factors (probiotics and milk antigen exposure) and their relationship to regulatory T cell responses are all poorly defined. Therefore, there is an unmet need to identify dietary interventions, along with corresponding immune responses, that favor the promotion of tolerance.

A major objective will be to measure the effect probiotics have on the development of tolerance to milk antigen over time. By following these infants during the first year of life, and repeatedly collecting blood and stool samples from them, we will be poised to analyze their stool microbiome signatures, and we will estimate the frequency, phenotype and TCR diversity of milk-specific T cells over time. By repeatedly challenging them with more immunologically intact milk protein, we will better define the kinetics of CMA resolution and its association to these variables. This information is likely to further elucidate CMA disease mechanisms and identify possible biomarkers of disease resolution versus persistence. It will be directly useful for evaluating the efficacy of pro
Sponsor: Massachusetts General Hospital

Current Primary Outcome: The percentage of subjects who develop tolerance to cow's milk protein by 12 months post randomization to study formula. [ Time Frame: 12 months post randomization ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Safety as assessed by adverse events graded using the NCI-CTCAE scale by treatment group. [ Time Frame: 36 months ]
    The rate of reported adverse events by treatment group.
  • Tolerance as assessed by the transcriptional profile of milk-specific T cells by clinical outcome. [ Time Frame: 36 months ]
  • Tolerance as assessed by weight for age Z-scores. [ Time Frame: 36 months ]
  • Tolerance as assessed by length for age Z-scores. [ Time Frame: 36 months ]
  • Tolerance as assessed by weight for length Z-scores. [ Time Frame: 36 months ]
  • Tolerance as assessed by stool consistency using the Bristol Stool Chart. [ Time Frame: 36 months ]
  • Tolerance as assessed by stool frequency. [ Time Frame: 36 months ]
  • Tolerance as assessed by changes in the stool microbiome. [ Time Frame: 36 months ]
  • Tolerance as assessed by the estimated frequency of milk-specific T cells by clinical outcome. [ Time Frame: 36 months ]
  • Tolerance as assessed by the TCR diversity of milk-specific T cells by clinical outcome. [ Time Frame: 36 months ]
  • Tolerance as assessed by the milk allergen component-specific IgE, IgG4 and IgA by clinical outcome. [ Time Frame: 36 months ]


Original Secondary Outcome: Same as current

Information By: Massachusetts General Hospital

Dates:
Date Received: October 30, 2015
Date Started: February 2016
Date Completion: February 2019
Last Updated: March 21, 2016
Last Verified: March 2016