Clinical trial NCT06683521: Immunologic Basis of Food Protein-Induced Enterocolitis Syndrome
Official title: Immunologic Basis of Food Protein-Induced Enterocolitis Syndrome
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Food Protein-Induced Enterocolitis Syndrome
Keywords: Allergy
FPIES
Food protein-induced enterocolitis syndrome
Food
Diagnosis
Lead sponsor: NYU Langone Health
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2024-11-12
Enrollment: 72
Sex: ALL
Minimum age (years): 1
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: DIAGNOSTIC

Brief summary: This is a phase I multicenter clinical trial that aims to find the optimal dose for conducting a novel low-dose, multi-day oral food challenge (OFC) protocol for diagnosing food protein-induced enterocolitis syndrome (FPIES). Individuals ages 1-60 years with a history of suspected or confirmed FPIES will be eligible for enrollment. Recruitment is expected to occur over 3 years.

Detailed description: At the time of enrollment, participants will undergo screening (Visit 0) and complete a baseline gastrointestinal symptom diary.

At Visit 1 (Day 1), participants will undergo a supervised Low Dose OFC to their FPIES trigger. Those who react will be considered low-threshold reactors and recommended to continue strict avoidance of their FPIES trigger.

For participants who do not react at the Day 1 Low Dose OFC, continued participation involves a daily home challenge on Days 2-7. Participants will be provided with a diary to monitor symptoms. If objective or persistent subjective symptoms develop, participants will be advised to contact the study team before consuming any further doses.

Participants will return for Visit 2 on Day 8. Those who reported symptoms that led to discontinuation of the home challenge will undergo biospecimen collection. Those who tolerated the Day 1 supervised and Days 2-7 home challenges will undergo a High Dose OFC to their suspected FPIES trigger. Those who tolerate this challenge will be considered to have outgrown their FPIES and instructed to introduce the food regularly at home. Those who react will be considered high-threshold reactors and advised to continue strict avoidance of their FPIES trigger and continue routine allergy care.

Eligibility criteria: Inclusion Criteria:

* Provision of appropriate consent and/or assent
* Age 1-60 years
* Suspected or confirmed FPIES diagnosis
* Reported convincing FPIES reaction (per criteria in 2017 FPIES guidelines) within: (Children \<18 years of age: The past 6-36 months) (Adults age \>18 years: The past 6 months-10 years)
* Individuals of childbearing potential practicing sexual abstinence or using effective methods of contraception during study participation
* English-speaking

Exclusion Criteria:

* Past severe FPIES defined as hospitalization due to an acute FPIES reaction with neurological compromise or requiring life support
* Acute FPIES reaction in the past 6 months
* Frequent gastrointestinal symptoms: nausea, abdominal pain, reflux, heartburn, emesis, diarrhea, constipation per participant or guardian report or as evidenced by FPIES Symptoms Score (FPIES-SS)
* Current active eosinophilic gastrointestinal disorders, inflammatory bowel disease, gastroesophageal reflux disease, or any other chronic gastrointestinal condition
* Poorly controlled atopic dermatitis at screening per PI discretion
* Poorly controlled or severe asthma/wheezing at screening, defined by at least one of the following criteria: 1: History of two or more systemic corticosteroid courses within six months of screening or one course of systemic corticosteroids within three months of screening to treat asthma/wheezing; 2: Prior intubation/mechanical ventilation for asthma/wheezing; 3: One hospitalization or ED visit for asthma/wheezing within six months of screening; and 4: Inhaled corticosteroid (ICS) dosing of \>500 mcg daily fluticasone (or equivalent ICS based on National Heart, Lung, and Blood Institute (NHLBI) dosing chart).
* IgE-mediated food allergies where the trigger has not been identified
* Inability to discontinue prohibited medications for 7 days prior to the screening visit and lasting for the duration of study participation unless indicated for use as rescue medication
* Personal or family history of prolonged QT syndrome
* Personal history of arrhythmia
* Current diagnosis of arterial hypertension
* Current diagnosis of cardiovascular disease
* Current diagnosis of any chronic autoimmune disease
* Current diagnosis of liver disease
* Primary or secondary immunodeficiency
* Phenylketonuria (PKU) (ondansetron tablets may contain phenylalanine)
* Use of systemic steroids within 30 days of screening
* Chemotherapy, radiotherapy, or any systemic immunosuppressive drugs in the past 12 months
* Use of biologic drugs or allergen-specific immunotherapy by any route in the past 12 months
* Inability to defer routine immunizations or passive immunization with immune globulin for the duration of participation in the study
* Allergy to any of the following medications: ondansetron (Zofran), dolasetron (Azemet), granisetron (Kytril), or palonosetron (Aloxi)
* Pregnancy or breastfeeding
* Current or past medical problems or findings from the physical examination or screening evaluation not listed above, which, in the opinion of the investigator(s), may pose additional risks from study participation, interfere with the participant's ability to comply with study requirements, and/or impact the quality or interpretation of the data obtained from the study

Primary outcomes:
measure: The proportion of individuals with active FPIES who develop FPIES symptoms during the optimal Low Dose multi-day OFC (Days 1-7)
timeFrame: Up to Day 7
Secondary outcomes:
measure: Percentage of participants who meet criteria for intravenous fluid (IVF) resuscitation among those who develop FPIES symptoms during Low Dose multi-day OFC (Days 1-7)[Time Frame: Up to Day 7]
timeFrame: Up to Day 7
measure: Percentage of participants treated with oral ondansetron among those who develop FPIES symptoms during Low Dose multi-day OFC
timeFrame: Up to Day 7
measure: Percentage of participants treated with parenteral ondansetron among those who develop FPIES symptoms during Low Dose multi-day OFC
timeFrame: Up to Day 7
measure: Percentage of participants with hypotension among those who develop FPIES symptoms during Low Dose multi-day OFC (Days 1-7)
timeFrame: Up to Day 7
measure: Percentage of participants with reactions treated in the Emergency Department (ED) among those who develop FPIES symptoms during Low Dose multi-day OFC (Days 1-7)
timeFrame: Up to Day 7
measure: Number of participants with reactions resulting in overnight admission to ED/Hospital among those who develop FPIES symptoms during Low Dose multi-day OFC (Days 1-7)
timeFrame: Up to Day 7
measure: Median number of emesis episodes among those who develop FPIES symptoms during Low Dose multi-day OFC (Days 1-7)
timeFrame: Up to Day 7
measure: Median maximum severity of abdominal pain score (assessed with the FPIES-SS) among those who develop FPIES symptoms during Low Dose multi-day OFC (Days 1-7)
timeFrame: Up to Day 7
measure: Median time to discharge during Day 1 Supervised Low Dose OFC among those who develop FPIES symptoms during Low Dose multi-day OFC
timeFrame: Day 1
measure: Median time to resolution of symptoms during Day 1 Supervised Low Dose OFC among those who develop FPIES symptoms during Low Dose multi-day OFC
timeFrame: Day 1
Other outcomes:
Locations:
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: New York
country: United States
facility: Jaffe Food Allergy Institute at Mount Sinai
state: New York
Study officials:
affiliation: NYU Langone Health
name: Anna Nowak-Wegrzyn, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: