This is a double-blind, crossover food challenge study using pork with and without α-gal in patients with a clinical diagnosis of gastrointestinal (GI)- α-gal allergy, and to investigate the pathophysiology underlying their symptoms.
Each participant will be randomized to undergo two double-blind food challenges with at least a 10-day washout period between the challenges. One food challenge will contain pork meat with alpha gal sugar; one challenge will contain pork meat without the alpha gal sugar. During the challenges, participants will drink lactulose and C13 mannitol dissolved in water. The principal investigator and clinical research coordinators will be blinded to the challenges during the course of the study. The metabolic kitchen and a delegated research staff member will be unblinded. On consenting patients, a transnasal upper endoscopy (TNE) will be performed on each challenge day, pre-challenge, at hour 0 and post-challenge, at hour 6. During the TNE, esophagus, stomach and small bowel samples will be collected. Gastrointestinal pathology samples will be evaluated for inflammatory cells and also biobanked for further messenger RNA (mRNA) sequencing studies. Blood and urine will be collected during each challenge. Samples will be transported to a lab and analyzed for tryptase, basophil activation, and lactulose/ mannitol levels.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
QUADRUPLE
Enrollment
30
150 grams of cooked, ground pork meat containing alpha-gal sugar eaten once
150 grams of cooked, ground pork meat not containing alpha-gal sugar
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States
RECRUITINGAllergic reaction (food challenge positive)
Presence of allergic reaction within 6 hours of the challenge. Reported as dichotomous: food challenge positive (reaction) or food challenge negative (no reaction).
Time frame: 6 hours post ingestion
No allergic reaction (food challenge negative)
No allergic reaction within 6 hours of the challenge. Reported as dichotomous: food challenge positive (reaction) or food challenge negative (no reaction).
Time frame: 6 hours post ingestion
Lactulose excretion
C13 mannitol quantification with high-performance liquid chromatography- C13 mannitol excreted in the urine in the six hours following ingestion will be measured as a marker of intestinal permeability.
Time frame: 0- 6 hours post ingestion
C13 mannitol excretion
C13 mannitol quantification with high-performance liquid chromatography- C13 mannitol excreted in the urine in the six hours following ingestion will be measured as a marker of intestinal permeability.
Time frame: 0-6 hours post ingestion
Basophil activation threshold response at timepoint 0
Basophil activation threshold responses - peripheral blood basophils will be isolated and stimulated with mammal-based extracts to create a dose-response curve for concentrations of antigen leading to CD63 activation
Time frame: 0 hours (prior to ingestion)
Basophil activation threshold response at 2 hours
Basophil activation threshold responses - peripheral blood basophils will be isolated and stimulated with mammal-based extracts to create a dose-response curve for concentrations of antigen leading to CD63 activation.
Time frame: 2 hours post ingestion
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Basophil activation threshold response at 4 hours
Basophil activation threshold responses - peripheral blood basophils will be isolated and stimulated with mammal-based extracts to create a dose-response curve for concentrations of antigen leading to CD63 activation.
Time frame: 4 hours post ingestion
Basophil activation threshold response at 6 hours
Basophil activation threshold responses - peripheral blood basophils will be isolated and stimulated with mammal-based extracts to create a dose-response curve for concentrations of antigen leading to CD63 activation. Results pre- and post- pork challenge will be compared to assess for changes in basophil responses
Time frame: 6 hours post ingestion
Serum tryptase at timepoint 0
Serum tryptase- serum tryptase levels will be quantified.
Time frame: 0 hours (prior to ingestion)
Serum tryptase at 2 hours
Serum tryptase- serum tryptase levels will be quantified.
Time frame: 2 hours post ingestion
Serum tryptase at 4 hours
Serum tryptase- serum tryptase levels will be quantified.
Time frame: 4 hours post ingestion
Serum tryptase at 6 hours
Serum tryptase- serum tryptase levels will be quantified.
Time frame: 6 hours post ingestion
Mast cell count on stomach biopsies (per high powered field (hpf))
The number of mast cells will be counted at high-powered field on biopsy specimens of the stomach.
Time frame: 6 hours post ingestion
Mast cell count on small bowel biopsies (per high powered field (hpf))
The number of mast cells will be counted at high-powered field on biopsy specimens of the small bowel.
Time frame: 6 hours post ingestion
Eosinophil cell count on stomach biopsies (per high powered field (hpf))
The number of eosinophil cells will be counted at high-powered field on biopsy specimens of the stomach.
Time frame: 6 hours post ingestion
Eosinophil cell count on small bowel biopsies (per high powered field (hpf))
The number of eosinophil cells will be counted at high-powered field on biopsy specimens of the small bowel.
Time frame: 6 hours post ingestion
GI Symptom Rating Score (GSRS)
The Gastrointestinal Symptom Rating Scale (GSRS) assesses gastrointestinal symptoms as experienced by participants in the 24-hours following a challenge. The scale covers 17 specific G1 symptoms, each rated on a 0-5 scale where 0 (no symptoms), 1 (very mild), 2 (mild), 3 (moderate), 4 (severe), 5 (very severe)
Time frame: 24 hours post challenge