GI Alpha-Gal Study

NCT06268717 | Recruiting

• 1 other identifier: 23-0316
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Alpha-Gal Syndrome; Irritable Bowel Syndrome; Diarrhea; Abdominal Pain; Vomiting

Keywords

Alpha-Gal Syndrome; diarrhea; abdominal pain; vomiting

Outcome Measures

Primary Outcomes (16)

• 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

Secondary Outcomes (1)

• GI Symptom Rating Score (GSRS)

  24 hours post challenge

Study Arms (2)

Food challenge with pork meat containing alpha-gal, then pork meat without alpha gal sugar

ACTIVE COMPARATOR

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; Other: Pork meat not containing alpha-gal

Food challenge with pork meat without alpha gal sugar, then pork meat containing alpha-gal

ACTIVE COMPARATOR

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; Other: Pork meat not containing alpha-gal

Interventions

Ground pork containing alpha-gal OTHER

150 grams of cooked, ground pork meat containing alpha-gal sugar eaten once

Food challenge with pork meat containing alpha-gal, then pork meat without alpha gal sugar; Food challenge with pork meat without alpha gal sugar, then pork meat containing alpha-gal

Pork meat not containing alpha-gal OTHER

150 grams of cooked, ground pork meat not containing alpha-gal sugar

Food challenge with pork meat containing alpha-gal, then pork meat without alpha gal sugar; Food challenge with pork meat without alpha gal sugar, then pork meat containing alpha-gal

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 6 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.

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• Revivicor, Inc: collaborator

Study Sites (1)

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

RECRUITING

MeSH Terms

Conditions

red meat allergy; Irritable Bowel Syndrome; Diarrhea; Abdominal Pain; Vomiting

Condition Hierarchy (Ancestors)

Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations

Study Officials

• Sarah McGill, MD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sarah McGill, MD

CONTACT

+1 (919) 966-7047; mcgills@email.unc.edu

Shilpa Karanjit, MPH

CONTACT

919-843-8519; Shilpa_Karanjit@med.unc.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Double-blind crossover. 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 containing alpha-gal sugar; one challenge will contain pork meat without alpha-gal sugar.

Study Record Dates

• First Submitted: February 12, 2024
• First Posted: February 20, 2024
• Study Start: October 17, 2023
• Primary Completion (Estimated): June 2, 2026
• Study Completion (Estimated): June 2, 2026
• Last Updated: October 20, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: beginning 9 and continuing for 36 months following publication
• Access Criteria: Investigator has approved IRB, IEC, or REB and an executed data use/sharing agreement with UNC.

Locations

US (1)