Molecular Basis of Food Allergy

• ClinicalTrials.gov Identifier: NCT01832324
• Recruitment Status: Enrolling by invitation
• First Posted: April 16, 2013
• Last Update Posted: November 18, 2023
• Sponsor: Children's Hospital of Philadelphia
• Collaborators: University of Pennsylvania; National Institute of Allergy and Infectious Diseases (NIAID); Children's Hospital Medical Center, Cincinnati
• Information provided by (Responsible Party): Children's Hospital of Philadelphia

Study Description

Brief Summary:

The Study examines the molecular basis of food allergy. It explores the interaction between T cells, InKT cells and cytokines in the development of food allergy. The study also explores these factors in development of tolerance "outgrowing" food allergy. It will also explore the genetic factors that lead to the development of food allergy.

The study examines all type of food allergy including IgE mediated reactions, Eosinophilic Esophagitis and Food Protein Induced Enterocolitis

Condition or disease
Food Allergy; Eosinophilic Esophagitis

Detailed Description:

Food Allergy (FA) is a common pediatric atopic disease. Characteristically children affected by FA become sensitized to food in the first few months of life and spontaneously outgrow the disease by 5-6 years of age in about 80% of cases. At the present time, diagnosis of FA is made by a combination of history, skin testing and food challenge. The pathogenic mechanisms leading to food sensitization and subsequent spontaneous tolerance development are not understood.

Study Design

• Study Type: Observational
• Estimated Enrollment: 5300 participants
• Observational Model: Case-Control
• Time Perspective: Prospective
• Official Title: Molecular Basis of Food Allergy and Food Tolerance
• Study Start Date: January 2011
• Estimated Primary Completion Date: December 2027
• Estimated Study Completion Date: December 2030

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :

1. Blood sample for mechanistic studies: [ Time Frame: 1 year ]
   Blood will be obtained by venipuncture. The blood samples will be used to estimate the frequency of to estimate the frequency and the products of cells involved in the allergic reaction. We will quantify the number of lymphocytes and their subsets, and the number granulocytes (neutrophils, basophils, and eosinophils) and monocytes and we will analyze their products (such as cytokines, chemokines, prostanoids). Such analysis will be performed doing cytoflow studies, using 4 color flow cytometry (BD FACSCalibur Flow XCytometry System) at the Children's Hospital Flow Cytometry core facilities, ELISA, mRNA analysis and western blots using when indicated the Nucleic Acid/Protein Core. If blood won't be all used up in the aforementioned tests it will be stored in nitrogen liquid for future similar tests or repetition of the ones already performed in case of technical problem with the first attempt.
2. Blood sample for genetic study (optional) [ Time Frame: 1 year ]

   The Center for Applied Genomics (CAG) will perform genetic analysis. All subjects (cases and controls) have been or will be genotyped on the Illumina HumanHap BeadArray SNP platform, and data has been stored in following an IRB approved protocol

   Whole Exon Sequencing (also known as targeted exome capture) is an efficient strategy to selectively sequence the coding regions of the genome as a cheaper but still effective alternative to whole genome sequencing. Exons are short, functionally important sequences of DNA which represent the regions in genes that are translated into protein and the untranslated region flanking them (UTR). It is estimated that the protein coding regions of the human genome constitute about 85% of the disease-causing mutations.

   Statistical analysis will be done in conjunction with CAG and Children's Hospital of Philadelphia (CHOP) bioinformatics center. We will compare the genetic variants identified between sequencing and SNPs -based genotyping.

3. EndoPat Test (optional) [ Time Frame: 1 year ]
   EndoPat is a noninvasive endothelial function assessment. Patient should rest comfortably for 10 minutes prior to the test. Using a standard blood pressure cuff, the brachial artery is occluded for a 5 minute period. When the cuff is released, EndoPat measures blood flow rates pre-occlusion and post-occlusion. This test requires patients to sit still for 15 minutes. It's recommended that the patient fast 3 to 8 hours before the test. In addition, the following drugs should not be used for 24 hours before testing: Nitroglycerine, Alpha-blockers, beta-blockers, and calcium channel blockers, ACE inhibitors, Statins

Biospecimen Retention:   Samples With DNA

DNA, sera and PBMC

Eligibility Criteria

• Ages Eligible for Study: 1 Month to 65 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Probability Sample

Study Population

Food Allergy (Both IgE and Non-IgE Mediated) Atopic Controls Healthy controls

Criteria

Inclusion Criteria for Study Group:

1. Males or females age 1 month to 65 years.
2. Diagnosis of Food Allergy. Food Allergy can be either IgE or non-IgE mediated food allergy including Eosinophilic Esophagitis and Food Protein Induced Enterocolitis.

Inclusion Criteria for Control group:

1. Age and sex matched patients without food allergies
2. Sibling and parents of patients with food allergies

Inclusion Criteria for Control group with atopy:

1. Age and sex matched patients without food allergies
2. Sibling and parents of patients with food allergies
3. Patients with atopy

Exclusion Criteria

1. Underlying disease or medical problem that is judged to serious or risky to allow 3 ml/kg of blood to be drawn from a vein (such as serious anemia, cancer, poor vein abscess, serious infections).
2. Subjects that do not meet the enrollment criteria may not be enrolled. Any violations of these criteria will be reported in accordance with Institutional Review Board (IRB) policies and procedures study procedures.

Contacts and Locations

Locations

United States, Pennsylvania

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States, 19104

Sponsors and Collaborators

Children's Hospital of Philadelphia

University of Pennsylvania

National Institute of Allergy and Infectious Diseases (NIAID)

Children's Hospital Medical Center, Cincinnati

Investigators

• Principal Investigator: Jonathan M Spergel, MD, PhD; Children's Hospital of Philadelphia

More Information

• Responsible Party: Children's Hospital of Philadelphia
• ClinicalTrials.gov Identifier: NCT01832324
• Other Study ID Numbers: 08-005998; R01AI097333-01A1 ( U.S. NIH Grant/Contract )
• First Posted: April 16, 2013
• Last Update Posted: November 18, 2023
• Last Verified: November 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: Deidentiifed data including specific IgE, results of basophil assay and what individual food that the patient is reacting to will be included.

Keywords provided by Children's Hospital of Philadelphia:

Food Allergy; Eosinophilic Esophagitis; Food Protein Induced Enterocolitis; iNKT Cells; T cells

Additional relevant MeSH terms:

Esophagitis; Eosinophilic Esophagitis; Hypersensitivity; Food Hypersensitivity; Immune System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Gastroenteritis; Hypersensitivity, Immediate; Eosinophilia; Leukocyte Disorders; Hematologic Diseases