This trial is active, not recruiting.

Condition peanut allergy
Treatments peanut flour, oat flour
Phase phase 1/phase 2
Sponsor Massachusetts General Hospital
Collaborator National Institute of Allergy and Infectious Diseases (NIAID)
Start date May 2013
End date September 2017
Trial size 40 participants
Trial identifier NCT01750879, 2012P002153, 5U19AI095261-02


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).

United States No locations recruiting
Other countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator)
Primary purpose basic science
(Active Comparator)
Oral Immunotherapy with peanut flour.
peanut flour
Peanut Flour
(Placebo Comparator)
Oral Immunotherapy with oat flour.
oat flour
Oat Flour

Primary Outcomes

The change in the percentage of induced Treg cells (CD45RA- CD25++ FoxP3++ of CD4+ T cells) from baseline to the end of maintenance therapy.
time frame: 518 days

Secondary Outcomes

Clinical: Tolerance
time frame: 630 days
Clinical: Desensitization
time frame: 518 days
Clinical: Safety
time frame: 630 days
Mechanistic: TCR clonal diversity
time frame: 630 days
Mechanistic: Change eliciting dose of end-point dilution.
time frame: 518 days
Mechanistic: Change in basophil eliciting dose.
time frame: 630 days
Mechanistic: Change in peanut allergen-specific IgG4
time frame: 518 days
Mechanistic: Significant gene expression changes by transcriptional profiling of regulatory and effector T cell participants
time frame: 630 days

Eligibility Criteria

Male or female participants from 7 years up to 55 years old.

Inclusion Criteria: - Diagnosis of peanut allergy by a positive skin prick test to peanut (reaction wheal at least 5 mm larger than saline control) and by medical history or Serum peanut-specific IgE >5 kU/L at screening visit. - Ara h 2 specific IgE >0.35 kU/L at screening visit - Ability to provide informed consent. - Males and females of all ethnic/racial groups aged 7-55 years old who are otherwise healthy. - React to less than 443 mg of peanut protein during DBPCFC1 Exclusion Criteria: - History of severe anaphylaxis as defined by hypoxia (cyanosis or SpO2 <92% during reaction), documented hypotension (documented systolic BP >30% below predicted normal for sex, height, weight or from known baseline), neurological compromise (confusion, loss of consciousness), or incontinence. - Severe or Moderate asthma as defined using the severity criteria of the current NHBLI Guidelines for the Diagnosis and Management of Asthma (http://www.nhlbi.nih.gov/guidelines/asthma/). - Poorly-controlled asthma as defined by FEV1 <80% or any of the following symptoms: nighttime awakening >2 days/week or rescue medication use >2 days / week. - Diagnosis of other severe or complicating medical problems, including autoimmune or chronic immune inflammatory conditions or gastrointestinal inflammatory conditions, including Celiac Disease, Inflammatory Bowel Disease and Eosinophilic Gastrointestinal Disorders - Inability to cooperate with and/or perform oral food challenge procedures. - Primary Immune Deficiency - Allergy to oat confirmed by skin prick testing and history - Current use of beta blockers, angiotensin converting enzyme inhibitors, or monoamine oxidase inhibitors - Women of childbearing potential who are pregnant, planning to become pregnant, or breastfeeding - Hemoglobin level less than 12.5 gm/dL at screening. Weight <23 kg - Use within the past 6 months of other systemic immunomodulatory treatments including allergen immunotherapy, or use of biologics with an immune target, including omalizumab. - Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study may also exclude a participant from the study.

Additional Information

Official title Clinical Desensitization and Tolerance Following Peanut Oral Immunotherapy and Subsequent Allergen Avoidance
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.
Trial information was received from ClinicalTrials.gov and was last updated in May 2016.
Information provided to ClinicalTrials.gov by Massachusetts General Hospital.