Immunopathogenesis of Food Allergy and Eosinophilic Gastrointestinal Disorders

NCT01212016 | Terminated

• 2 other identifiers: 10019610-I-0196
• Study Type: observational
• Target: 162
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- Food allergies are characterized by abnormal immune system responses to certain foods, such as peanuts, strawberries, and shellfish. Some individuals with these allergies have immediate allergic reactions on contact with the food in question and need immediate treatment to prevent severe complications. In contrast, eosinophil-associated gastrointestinal disorders are related disorders in which white blood cells in the intestinal tract react to certain foods, causing abdominal pain, nausea, and other digestion problems. Researchers are interested in studying these conditions to better understand how the immune system responds to food allergies. Objectives:

• To examine how the immune system responds to food allergens.
• To examine how certain white blood cells contribute to disease in individuals with food allergies and other inflammatory diseases. Eligibility:
• Individuals between 18 and 65 years of age who have a history of (a) severe allergic reaction to peanuts (and have peanut-specific antibodies), (b) allergy or inflammatory disease, or (c) eosinophil-associated gastrointestinal disorder (with at least two documented food allergies).
• Healthy volunteers between 18 and 65 years of age who have no known allergies or asthma. Design:
• All participants will have a screening visit and a procedure visit. The procedure visit will take place within 30 to 60 days of the screening visit, and will take 3 to 4 hours depending on the procedure(s) done.
• Participants will be screened with a physical examination and medical history, and will provide blood samples for testing. Participants with peanut or other allergies will have additional tests to determine their levels of sensitivity to certain foods. Participants with eosinophil-associated gastrointestinal disorder will provide stool samples for testing.
• At the procedure visit, participants with peanut allergies and participants with other allergies will provide blood samples and have leukapherisis to collect white blood cells for examination.
• At the procedure visit, healthy volunteers and participants with eosinophil-associated gastrointestinal disorder will provide blood samples and have leukapherisis to collect white blood cells for examination. In addition, some but not all of these participants will have a procedure called esophagogastroduodenoscopy (EGD), which will examine the esophagus, stomach, and small intestine. Participants who are scheduled to have EGD will be asked to fast for 6 hours before the procedure.

Conditions

Eosinophilic Gastroenteritis; Eosinophilic Esophagitis

Keywords

Eosinophilic Esophagitis; Eosinophilic Gastroenteritis; Peanut Allergy; T Cell; IgE; Food Allergy

Outcome Measures

Primary Outcomes (3)

• Quantitation of gut tissue IL-5+ and IL-5- Th2 cells in EGIDs and in healthy non-atopic subjects.

  End of study

• Quantitation of gut tissue Th2 cells using alternative techniques (GATA3 immunohistochemistry, RT-PCR) in EGIDs and in healthy non-atopic subjects.

  End of study

• Quantitation of gut tissue IFN-, IL- 17 and IL-10 producing cellpopulations in EGIDs and in healthy non-atopic subjects.

  End of study

Secondary Outcomes (2)

• Characterization of gut homing food allergen specific T cells

  End of study

• Characterization of Pro-anaphylactic follicular helper Th2 cells in foodallergy

  End of study

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All Subjects must:
• Be willing to have samples collected and stored for future research.
• Have a documented clinical history compatible with EGID, peanut allergy, or other allergic and inflammatory diseases or be healthy without known allergic conditions.
• Subjects with EGID must:
• Be greater than or equal to 18 years of age
• Maintain a primary non-NIH physician for routine care
• Have one of the types of EGID below:
• Eosinophilic gastroenteritis: Have a clinical history of eosinophilic gastroenteritis -including gastrointestinal symptoms-, and histological evidence of stomach or duodenal eosinophilia with no other known etiology for the eosinophilia despite careful clinical evaluation.
• Eosinophilic esophagitis: Have a diagnosis of eosinophilic esophagitis, including evidence of esophageal dysfunction with a peak count of greater than or equal to 25 eosinophils per high powered field, for which the biopsy was obtained while under proton pump inhibitor treatment.
• Probable eosinophilic esophagitis: Have a likely diagnosis of eosinophilic esophagitis, based on evidence of esophageal dysfunction and a peak count of greater than or equal to 15 eosinophils per high powered field, but for which the biopsy was not obtained under proton pump inhibitors (per section 6.3). To confirm
• a diagnosis of EoE, these subjects may be treated with proton pump inhibitor therapy at recommended doses for gastroesophageal reflux disease for at least 84 weeks prior to EGD and biopsy. The decision to recommend diagnostic biopsy will be according to concensus guidelines \[7\] and current standards of care: based on the severity of symptoms, history of food impactions, and evidence of remodeling (strictures).
• Subjects with Peanut Allergy:
• Be greater than or equal to 18 years of age and less than or equal to 65 years of age.
• Have a history of immediate hypersensitivity to peanuts with involvement of at least one extracutaneous site, including wheezing, laryngeal edema, angioedema, vomiting, diarrhea, hypotension and circulatory collapse.
• Have peanut specific IgE of greater than or equal to 5 kIU/L.

You may not qualify if:

• Subjects with any of the following criteria will be excluded:
• \. Any other condition that, in the investigator s opinion, places the subject at undue risk by participating in the study
• Subjects with Peanut Allergy with any of the following will be excluded:
• \. Chronic upper GI symptoms that are consistent with EGID (dysphagia, nausea, vomiting, abdominal pain/cramps, early satiety)
• Subjects with EoE and EG undergoing research EGD or lymphapheresis must:
• \. Be greater than or equal to 18 years of age and less than or equal to 65 years of age.
• Subjects with EG undergoing EGD or lymphapheresis must have:
• Histological evidence of stomach or duodenal eosinophilia with a peak count greater than or equal to 40 eosinophils per high powered field
• Greater than two positive allergen skin tests or antigen specific IgE tests out of the following panel (peanut, wheat, soy, shrimp, egg white, milk, walnut, cod, corn)
• Subjects with either EG or EoE undergoing lymphapheresis must have:
• \. An absolute eosinophil count of \>750 eos/microL at least once in the last 2 years
• Subjects with EoE undergoing EGD must have:
• Diagnosed EoE per section 5.1 with a previous biopsy showing greater than or equal to 25 eosinophils per high powered field, OR
• Probable eosinophilic esophagitis per section 5.1 with a previous biopsy showing greater than or equal to 25 eosinophils per high powered field
• Subjects with any of following will not undergo EGD:

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Furuta GT, Liacouras CA, Collins MH, Gupta SK, Justinich C, Putnam PE, Bonis P, Hassall E, Straumann A, Rothenberg ME; First International Gastrointestinal Eosinophil Research Symposium (FIGERS) Subcommittees. Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment. Gastroenterology. 2007 Oct;133(4):1342-63. doi: 10.1053/j.gastro.2007.08.017. Epub 2007 Aug 8.

  PMID: 17919504 BACKGROUND

• Sicherer SH, Sampson HA. Food allergy: recent advances in pathophysiology and treatment. Annu Rev Med. 2009;60:261-77. doi: 10.1146/annurev.med.60.042407.205711.

  PMID: 18729729 BACKGROUND

• Sampson HA, Munoz-Furlong A, Campbell RL, Adkinson NF Jr, Bock SA, Branum A, Brown SG, Camargo CA Jr, Cydulka R, Galli SJ, Gidudu J, Gruchalla RS, Harlor AD Jr, Hepner DL, Lewis LM, Lieberman PL, Metcalfe DD, O'Connor R, Muraro A, Rudman A, Schmitt C, Scherrer D, Simons FE, Thomas S, Wood JP, Decker WW. Second symposium on the definition and management of anaphylaxis: summary report--Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium. J Allergy Clin Immunol. 2006 Feb;117(2):391-7. doi: 10.1016/j.jaci.2005.12.1303.

  PMID: 16461139 BACKGROUND

• Wansley DL, Yin Y, Prussin C. The retinoic acid receptor-alpha modulators ATRA and Ro415253 reciprocally regulate human IL-5+ Th2 cell proliferation and cytokine expression. Clin Mol Allergy. 2013 Dec 6;11(1):4. doi: 10.1186/1476-7961-11-4.

  PMID: 24314292 DERIVED

MeSH Terms

Conditions

Eosinophilic enteropathy; Eosinophilic Esophagitis; Peanut Hypersensitivity; Food Hypersensitivity

Condition Hierarchy (Ancestors)

Esophagitis; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Gastroenteritis; Eosinophilia; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Nut and Peanut Hypersensitivity

Study Officials

• Calman P Prussin, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2010
• First Posted: September 30, 2010
• Study Start: August 30, 2010
• Study Completion: May 13, 2015
• Last Updated: October 6, 2017

Record last verified: 2015-05-13

Locations

US (1)