GI Alpha-Gal Study

Understanding Gastrointestinal Alpha-Gal Syndrome: (GI Alpha-Gal Study)

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.

Study Overview

• Status: Recruiting
• Conditions: Vomiting; Irritable Bowel Syndrome; Abdominal Pain; Diarrhea; Alpha-Gal Syndrome
• Intervention / Treatment: Other: Ground pork containing alpha-gal; Other: Pork meat not containing alpha-gal

Detailed Description

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
• Enrollment (Estimated): 24
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sarah McGill, MD; Phone Number: +1 (919) 966-7047; Email: mcgills@email.unc.edu

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Recruiting
      • University of North Carolina at Chapel Hill
      • Contact: Sarah McGill, MD; Phone Number: 919-966-7047; Email: mcgills@email.unc.edu
      • Principal Investigator: Sarah McGill, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• The subject is at least 18 years of age.
• The subject has a history of gastrointestinal alpha-gal allergy defined by elevated test for α-gal allergy (α-gal IgE >0.1 U/L) due to complaints of either abdominal pain or discomfort, diarrhea, nausea with or without vomiting, or a combination of those complaints, within the last 5 years. The subjects must have experienced one or more of the four symptoms at least once monthly for at least two months. The subjects will fill out a symptom questionnaire of the presence of these four symptoms (abdominal pain or discomfort, diarrhea, nausea, vomiting), frequency and severity (mild, moderate, or severe) for the 3 months prior to diagnosis.
• The subject has experienced symptomatic improvement on a mammalian meat-free diet over at least a month's time, defined by saying "yes" to the following question: "On the alpha-gal avoidant diet, have you had adequate relief of gastrointestinal symptoms?"
• The subject has elevated α-gal IgE titer on screening for the trial if they do not have a positive titer within 3 months of enrollment.
• The subject is willing to not take nonsteroidal anti-inflammatory medications, leukotriene modifiers or steroids 14 days prior to challenge.
• The subject is willing to sign the informed consent form.

Exclusion Criteria:

• The subject has health conditions that would pose a significant threat in the face of anaphylaxis or treatment for anaphylaxis (e.g., cardiac disease, unstable angina pectoris, arrhythmias).
• The subject is allergic to mannitol.
• If female, the subject is pregnant.
• The subject has a history of chronic GI conditions, including inflammatory bowel disease, celiac disease, chronic pancreatitis with continued symptoms (experience moderate-severe abdominal pain, diarrhea, or nausea/vomiting that occur more frequently than once weekly)
• The subject has diarrhea (one or more loose stools that conform to the container), moderate to severe abdominal pain, or vomiting within 10 days prior to the challenge.
• The subject has a history of severe allergic reaction on mammalian meat ingestion (respiratory distress, chest pain or cardiopulmonary compromise)
• The subject is unwilling to receive intramuscular epinephrine.
• The subject is anticipated to use omalizumab within 6 months of enrollment.
• The subject is anticipated to use systemic steroids within 28 days of food challenge.
• The subject is anticipated to use leukotriene modifier within 14 days of food challenge.
• The subject is unable to not use nonsteroidal anti-inflammatory drugs for 14 days prior to challenge.

Additional Exclusion Criteria for Subjects Undergoing Transnasal Endoscopy and Biopsy

• Known conditions that are contraindications to transnasal endoscopy, or in the opinion of the investigator any condition that would interfere with the study objectives.
• History of head and neck malignancy or anatomical deformities of the nasopharynx
• Severe anxiety

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Food challenge with pork meat containing alpha-gal, then pork meat without alpha gal sugar; Participants receive a food challenge, consuming pork meat that contains alpha-gal. After a >10-day washout period, participants undergo a food challenge with pork which does not contain alpha-gal.	Other: Ground pork containing alpha-gal; 150 grams of cooked, ground pork meat containing alpha-gal sugar eaten once; Other: Pork meat not containing alpha-gal; 150 grams of cooked, ground pork meat not containing alpha-gal sugar
Active Comparator: Food challenge with pork meat without alpha gal sugar, then pork meat containing alpha-gal; Participants receive a food challenge consuming pork meat that does not contain alpha-gal sugar. After a >10-day washout period, participants undergo a food challenge with pork which does contain alpha-gal.	Other: Ground pork containing alpha-gal; 150 grams of cooked, ground pork meat containing alpha-gal sugar eaten once; Other: Pork meat not containing alpha-gal; 150 grams of cooked, ground pork meat not containing alpha-gal sugar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Allergic 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).	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).	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.	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.	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	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.	2 hours post ingestion
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.	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	6 hours post ingestion
Serum tryptase at timepoint 0	Serum tryptase- serum tryptase levels will be quantified.	0 hours (prior to ingestion)
Serum tryptase at 2 hours	Serum tryptase- serum tryptase levels will be quantified.	2 hours post ingestion
Serum tryptase at 4 hours	Serum tryptase- serum tryptase levels will be quantified.	4 hours post ingestion
Serum tryptase at 6 hours	Serum tryptase- serum tryptase levels will be quantified.	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.	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.	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.	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.	6 hours post ingestion

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: Revivicor, Inc
• Investigators: Principal Investigator: Sarah McGill, MD, University of North Carolina, Chapel Hill

Study record dates

Study Major Dates

• Study Start (Actual): October 17, 2023
• Primary Completion (Estimated): October 17, 2024
• Study Completion (Estimated): October 17, 2025

Study Registration Dates

• First Submitted: February 12, 2024
• First Submitted That Met QC Criteria: February 12, 2024
• First Posted (Actual): February 20, 2024

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 12, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: diarrhea; vomiting; abdominal pain; Alpha-Gal Syndrome
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Pain; Neurologic Manifestations; Disease; Signs and Symptoms, Digestive; Gastrointestinal Diseases; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Syndrome; Vomiting; Irritable Bowel Syndrome; Diarrhea; Abdominal Pain
• Other Study ID Numbers: 23-0316

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Deidentified individual data that supports the results will be shared beginning 9 to 36 months following publication provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with UNC.
• IPD Sharing Time Frame: beginning 9 and continuing for 36 months following publication
• IPD Sharing Access Criteria: Investigator has approved IRB, IEC, or REB and an executed data use/sharing agreement with UNC.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No