This is a multisite, randomized, double-blind, controlled cross-over trial with detailed characterization of participants with varying clinical sub-phenotypes of Alpha-gal Syndrome (AGS) who are then evaluated by oral food challenges with alpha-gal Knock Out (KO) pork versus Wild Type (WT) pork. Each participant will serve as their own control and ingest both alpha-gal-KO and WT pork on different days, with a minimum of an 8-day washout period between oral food challenges.
The primary objective is to determine whether the odds of positive challenges among participants with suspected alpha-gal syndrome are lower with alpha-gal Knock Out (KO) pork as compared to Wild Type (WT) pork during Double Blind Food Challenge (DBFC)
Able to understand and provide informed consent and/or have a parent or guardian able to understand and provide informed consent. Participants 12-17 years old must be able to provide assent
Participants who are willing to complete study procedures and follow-up
Have clinical history consistent with Alpha-gal Syndrome (AGS)
Have alpha-gal-specific Immunoglobin E (IgE) >= 0.1KU/L at screening
Unwilling to consume pork (native/wild type or genetically modified to no longer contain alpha-gal) during Double Blind Food Challenge (DBFC)
Have underlying health conditions suggesting that participants should not undergo an oral food challenge, including conditions that may be exacerbated by oral food challenge or treatment with epinephrine (e.g., history of ischemic heart disease, uncontrolled asthma, or cardiac arrhythmia)
Likely to move away from the study site prior to completion of follow up or do not have regular access to a phone
Have a history of severe anaphylaxis in response to pork or alpha-gal ingestion, defined as neurologic compromise or requiring intubation or cardiovascular compromise defined as myocardial infarction or other clinically significant cardiovascular events
Crossover
DBFC with 150g of Alpha-gal Knock Out (KO) pork
Diagnostic testEach participant will serve as their own control and ingest both alpha-gal-KO and WT pork on different days, with a minimum of an 8-day washout period between oral food challenges
DBFC with 150g of Wild Type (WT) pork
Diagnostic testEach participant will serve as their own control and ingest both alpha-gal-KO and WT pork on different days, with a minimum of an 8-day washout period between oral food challenges
Positive Double Blind Food Challenge (DBFC) result to 150 grams of either alpha-gal knockout (KO) pork or wild type (WT) pork.
A positive challenge will be defined as experiencing symptoms grade 2 or higher on the Consortium for Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions (scale range from 1 to 5, with higher scores indicating a more severe reaction) within 6 hours of ingestion.
Alpha-gal sub-phenotype as determined by symptoms resulting from Double Blind Food Challenge (DBFC) to wild-type (WT) pork.
Post-challenge alpha-gal sub-phenotypes as defined by reaction to their first DBFC to WT pork: anaphylaxis, cutaneous-only, or GI-only.
Gastrointestinal Symptom Rating Scale - Irritable Bowel Syndrome (GSRS-IBS) scores in response to 150 grams of Knock Out (KO) or Wild Type (WT) pork at each challenge visit
Validated patient-reported outcome measures: gastrointestinal symptoms based on GSRS-IBS score (score range from 15 to 105, with higher scores indicating a worse outcome).
Urticaria Activity Score (UAS7) in response to 150 grams of Knock Out (KO) or Wild Type (WT) pork at each challenge visit.
Validated patient-reported outcome measures: urticaria symptoms based on UAS7 score (score range from 0 to 42, with higher scores indicating a worse outcome).
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National Institute of Allergy and Infectious Diseases (NIAID)
Lead sponsor
Consortium for Food Allergy Research (CoFAR)
Collaborator
Allergy & Asthma Statistical and Clinical Coordinating Center: Rho, Inc
Collaborator
