Tolerance Following Peanut Oral Immunotherapy
Condition: Peanut Allergy
MeSH terms: Peanut Hypersensitivity
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The unifying objective of this project is to determine whether peanut oral immunotherapy (PN
      OIT) induced clinical tolerance in the context of food allergy is significantly associated
      with the expansion of a specific regulatory T cell subset (CD45RA- CD25++ FoxP3++) that is
      thought to be inducible in the gut-associated lymphoid compartment and associated with
      immunological tolerance.

      The hypothesis of the study is that the induction of Treg cells will be associated with
      clinical tolerance.

      The investigators will measure the change from baseline of induced Treg cells as a frequency
      of total CD4 T cells during active treatment and compare that between participants who
      achieve significant clinical tolerance (Tolerance and Partial Tolerance Groups as defined
      below) and those who do not (Treatment Failure Group).
    

Detailed description: 
      Clinical Objectives:

        1. To evaluate whether PN OIT induces increased tolerance, defined as a statistically
           significant increase in the median eliciting dose (ED) from a double-blind
           placebo-controlled food challenge (DBPCFC) before and after treatment with PN OIT and
           after subsequent allergen avoidance.

        2. To evaluate whether PN OIT induces clinical desensitization, defined as 1) a median
           10-fold or greater increase in ED at DBPCFC before and after PN OIT treatment period 2)
           a statistically significant higher median ED at DBPCFC following treatment period
           between active and control treatment; and 3) a significantly lower frequency of
           accidental ingestion reactions in active versus control treatment.

        3. To evaluate the safety of PN OIT.

      Mechanistic Objectives:

        1. To determine whether PN OIT induces a statistically significant increase in the TCR
           clonal diversity of Treg populations during active treatment among participants who
           achieve increased clinical tolerance (Tolerance and Partial Tolerance Groups as defined
           in clinical endpoints) versus the Treatment Failure Group.

        2. To determine whether PN OIT suppresses mast cells by inducing a significant suppression
           of the median ED on end-point dilution skin testing in actively treated participants by
           the end of maintenance therapy.

        3. To determine whether PN OIT suppresses basophils as defined by a 10-fold suppression of
           peanut-specific basophil ED in actively treated participants by end of a maintenance
           period.

        4. To determine whether either mast cell or basophil suppression at the end of maintenance
           therapy is significantly associated with clinical outcomes following avoidance.

      Exploratory Objectives:

        1. To describe the gene expression profiles and clonal diversity of regulatory and effector
           T cell subsets before and after OIT to better understand the phenotype and ontogeny of
           these subsets and potentially discover new therapeutic pathways.

        2. To engineer human MHC class II tetramers on common HLA backgrounds and map T cell
           epitopes of the dominant peanut allergens for use in validating earlier findings and for
           future studies of peanut-specific immune responses in humans.
    

Intervention name(s): Peanut Flour; Oat Flour
Intervention type(s): Drug; Drug
Intervention description(s): Peanut Flour; Oat Flour
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Basic Science
Keywords: peanut; allergy; food; immunotherapy; tolerance; desensitization