Allergy, Alpha-Gal Syndrome
Conditions
Keywords
Alpha-Gal Syndrome, Oral Food Challenge
Brief summary
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)
Interventions
DIAGNOSTIC_TESTDBFC with 150g of Alpha-gal Knock Out (KO) 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
DIAGNOSTIC_TESTDBFC with 150g of 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
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Consortium for Food Allergy Research (CoFAR)
Allergy & Asthma Statistical and Clinical Coordinating Center: Rho, Inc
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
DIAGNOSTIC
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
1. 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 2. Participants who are willing to complete study procedures and follow-up 3. Have clinical history consistent with Alpha-gal Syndrome (AGS) 4. Have alpha-gal-specific Immunoglobin E (IgE) \>= 0.1KU/L at screening 5. Report reaction consistent with AGS within the previous 24 months (prior to enrollment) 6. If with reproductive potential, agree to be abstinent or use an US Food and Drug Administration (FDA) approved method of birth control for the duration of the study 7. Willing to be trained on the proper use of a device for the self-administration of epinephrine (i.e., autoinjector or intra-nasal spray) and willing to have two doses available for the duration of the study
Exclusion criteria
1. Unwilling to consume pork (native/wild type or genetically modified to no longer contain alpha-gal) during Double Blind Food Challenge (DBFC) 2. 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) 3. Likely to move away from the study site prior to completion of follow up or do not have regular access to a phone 4. 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 5. Unwilling or unable to stop use of medications that may interfere with oral food challenge interpretation, reaction, or treatment for 5 half-lives prior to the challenge (e.g., antihistamines, beta blockers, Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) 6. Have used systemic immunomodulators (including biologics and monoclonal antibody therapy) within 6 months before study entry 7. Have underlying health conditions that may increase the chance of false positive challenges (e.g., inflammatory bowel disease, chronic urticaria, systemic mastocytosis, and mast cell activating syndrome) 8. Have used systemic steroids within 4 weeks of study entry 9. Have used any investigational agent within 6 months of study entry 10. Are on build-up of immunotherapy such as Antigen-based Immunotherapy (AIT), Oral Immunotherapy (OIT), Sublingual Immunotherapy (SLIT), or Epicutaneous Immunotherapy (EPIT) 11. Have reacted to mammalian products with onset of symptoms within 30 minutes of oral ingestion 12. Have current, diagnosed, mental illness or current, diagnosed or self-reported drug or alcohol abuse that, in the opinion of the investigator, would interfere with the participant's ability to comply with study requirements 13. Are pregnant or plan to become pregnant during the course of the study 14. Have 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, and/or may impact the quality or interpretation of the data obtained from the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Positive Double Blind Food Challenge (DBFC) result to 150 grams of either alpha-gal knockout (KO) pork or wild type (WT) pork. | At Visit 1 (within 2 months of screening) or Visit 2 (between 8 and 30 days of Visit 1) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Alpha-gal sub-phenotype as determined by symptoms resulting from Double Blind Food Challenge (DBFC) to wild-type (WT) pork. | At Visit 1 (within 2 months of screening) or Visit 2 (between 8 and 30 days of Visit 1) | 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 | At 7 days following completion of Double Blind Food Challenge (DBFC) at Visit 1 (within 2 months of screening) or Visit 2 (between 8 and 30 days of Visit 1) | 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. | At 7 days following completion of Double Blind Food Challenge (DBFC) at Visit 1 (within 2 months of screening) or Visit 2 (between 8 and 30 days of Visit 1) | Validated patient-reported outcome measures: urticaria symptoms based on UAS7 score (score range from 0 to 42, with higher scores indicating a worse outcome). |
Countries
United States
Contacts
STUDY_CHAIRLeonard Bacharier, M.D.
Vanderbilt University Medical Center: Division of Pediatric Allergy, Immunology, and Pulmonary Medicine
STUDY_CHAIRRachel Robison, M.D.
Vanderbilt University Medical Center: Division of Allergy, Pulmonary and Critical Care Medicine
Outcome results
None listed