Clinical trial NCT06268717: GI Alpha-Gal Study
Official title: Understanding Gastrointestinal Alpha-Gal Syndrome: (GI Alpha-Gal Study)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Alpha-Gal Syndrome
Irritable Bowel Syndrome
Diarrhea
Abdominal Pain
Vomiting
Keywords: Alpha-Gal Syndrome
diarrhea
abdominal pain
vomiting
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: Revivicor, Inc
First posted: 2024-02-20
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 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.
Primary purpose: OTHER

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Allergic reaction (food challenge positive)
timeFrame: 6 hours post ingestion
measure: No allergic reaction (food challenge negative)
timeFrame: 6 hours post ingestion
measure: Lactulose excretion
timeFrame: 0- 6 hours post ingestion
measure: C13 mannitol excretion
timeFrame: 0-6 hours post ingestion
measure: Basophil activation threshold response at timepoint 0
timeFrame: 0 hours (prior to ingestion)
measure: Basophil activation threshold response at 2 hours
timeFrame: 2 hours post ingestion
measure: Basophil activation threshold response at 4 hours
timeFrame: 4 hours post ingestion
measure: Basophil activation threshold response at 6 hours
timeFrame: 6 hours post ingestion
measure: Serum tryptase at timepoint 0
timeFrame: 0 hours (prior to ingestion)
measure: Serum tryptase at 2 hours
timeFrame: 2 hours post ingestion
measure: Serum tryptase at 4 hours
timeFrame: 4 hours post ingestion
measure: Serum tryptase at 6 hours
timeFrame: 6 hours post ingestion
measure: Mast cell count on stomach biopsies (per high powered field (hpf))
timeFrame: 6 hours post ingestion
measure: Mast cell count on small bowel biopsies (per high powered field (hpf))
timeFrame: 6 hours post ingestion
measure: Eosinophil cell count on stomach biopsies (per high powered field (hpf))
timeFrame: 6 hours post ingestion
measure: Eosinophil cell count on small bowel biopsies (per high powered field (hpf))
timeFrame: 6 hours post ingestion
Secondary outcomes:
measure: GI Symptom Rating Score (GSRS)
timeFrame: 24 hours post challenge
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Sarah McGill, MD
role: PRINCIPAL_INVESTIGATOR
References: