FARE Peanut SLIT and Early Tolerance Induction

• Status: Completed
• Trial end date: 2020-12-31
• Target enrollment: 0
• Participant gender: All

Summary

Primary Objective: To determine if 36 months of peanut SLIT as an early intervention in subjects ages 1 to 4 years induces clinical desensitization. The primary outcome of this objective will be a statistically significant difference in challenge scores between the treatment group versus the placebo group during DBPCFC (Double blind placebo controlled food challenge) performed after 36 months of peanut SLIT (desensitization). Challenge scores are measured by the amount of peanut protein participants are able to ingest successfully without symptoms of an allergic reaction. [Time Frame: Baseline, 36 months]

Secondary Objectives:

A secondary outcome of this objective will be a statistically significant difference in the challenge score of the treatment group versus the placebo group during the DBPCFC performed 3 months after discontinuing therapy (tolerance).

To examine the change in immune parameters associated with peanut SLIT and the development of clinical tolerance. Through this objective, the investigators will seek to understand the molecular processes by which SLIT affects the immune system through evaluation of immune mechanisms in relationship to clinical findings of desensitization and tolerance. The investigators will delineate the impact of peanut SLIT on the subsequent cellular and humoral responses to peanut protein: 1) peanut specific IgE, IgG, and IgG4 response, 2) peanut specific basophil activation, 3) mast cell responses through skin prick testing, and 4) specific T-cell cytokine responses and T regulatory cell (TReg) activation. The investigators anticipate that the effect of peanut SLIT will occur by induction of TRegs, conversion of T cells from an allergic (TH2) to a non-allergic (TH1) lymphocyte response (measured by cytokines, antibody levels, and skin prick test size), a change in peanut-specific basophil activation, or through a combination of the above.

[Time Frame: Baseline, 39 months]

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of North Carolina, Chapel Hill
• Collaborators: Food Allergy Research & Education; Food Allergy Research and Education (FARE); National Center for Complementary and Integrative Health (NCCIH); University of Texas Southwestern Medical Center
• Treatments: Glycerol

Criteria

Inclusion Criteria:

• Written informed consent from participant's parent/guardian.

• Age 12-48 months of either sex, any race, any ethnicity.

• A peanut allergy diagnosis with a convincing clinical history of peanut allergy and a serum peanut-specific IgE [UniCAP] > 0.35 kUA/L AND a positive skin prick test to peanut (>3 mm than the negative control) OR are sensitized to peanut (based on a serum IgE [UniCAP] to peanut of > 5 kUA/L) AND a positive skin prick test to peanut (> 3 mm than the negative control) and no known history of ingestion of peanut.

• A positive DBPCFC to 1000 mg of peanut at enrollment.

Exclusion Criteria:

• History of severe anaphylaxis to peanut, defined as hypoxia, hypotension, or neurologic compromise (cyanosis or SpO2 < 92% at any stage, hypotension, confusion, collapse or loss of consciousness).

• Participation in any interventional study for the treatment of food allergy in the past 6 months.

• Known oat, wheat, or glycerin allergy.

• Eosinophilic or other inflammatory (e.g. celiac) gastrointestinal disease.

• Severe asthma (2007 NHLBI Criteria Steps 5 or 6 - Appendix 2).

• Inability to discontinue antihistamines for skin testing and DBPCFCs.

• Use of omalizumab or other non-traditional forms of allergen immunotherapy (e.g., oral or sublingual) or immunomodulator therapy (not including corticosteroids) or biologic therapy within the past year.

• Use of beta-blockers (oral), angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor blockers (ARB) or calcium channel blockers.

• Significant medical condition (e.g., liver, kidney, gastrointestinal, cardiovascular, hematologic, or pulmonary disease) which would make the subject unsuitable for induction of food reactions.