Oral Immunotherapy for Food Protein Induced Enterocolitis Syndrome

NCT ID: NCT06614244

Last Updated: 2024-09-26

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 168 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-10-01
• Study Completion Date: 2028-03-31

Brief Summary

Food Protein Induced Enterocolitis Syndrome (FPIES) is a food allergy characterized by clinical manifestations of varying severity that can be, very rarely, severe to the point of leading to shock. Acute FPIES is nowaday the most common presentation of the disease. It is characterized by repeated, projectile vomiting (usually arising between 1 and 4 hours after ingestion of the culprit food) accompanied by pallor, hypotonia, and lethargy, with complete resolution of the aforementioned symptoms almost always within a few hours. Dietary management of FPIES currently involves avoiding allergens, offering complementary foods to encourage normal growth and providing families with individualized feeding plans. The elimination diet does not promote healing, it only prevents adverse reactions from culprit food ingestion. Recovery (i.e. tolerance to the culprit food) is achieved spontaneously over time. However, for some children, tolerance does not occur. These patients suffer from persistent FPIES. For these patients oral immunotherapy (OIT) is not yet planned and randomized and controlled studies are needed to demonstrate its efficacy and safety. The primary objective of the study will be to verify, with a multicenter, prospective, randomized study, stratified for the main 4 offending foods in Italy (cows milk, hens egg, fish and cereals), open-label and with an adequate sample size, the efficacy and safety of an OIT procedure in children affected by acute persistent FPIES. The comparison will be made between a population of children affected by acute persistent FPIES subjected to OIT for the offending food (DOPA group) and a population of children affected by acute persistent FPIES subjected to the traditional measure, i.e. the elimination diet for the offending food (Diet group).

Efficacy will be measured through:

• Comparison of the percentages of children who have increased their reactivity threshold even to the point of no adverse reactions to the offending food following the intake of a normal dose for their age in the two populations during treatment;
• Comparison of the percentages of children who have reached tolerance towards the culprit food in the two populations;

Safety will be measured through:

• Comparison of the percentages of children who have presented adverse reactions following the ingestion (accidental in the Diet group and expected in the DOPA group) of the culprit food after enrollment in the study.

The definitions of desensitization and tolerance are taken from the EAACI 2018 guidelines on immunotherapy for IgE-mediated AA. In particular, desensitization corresponds to the absence of adverse reactions following the ingestion of the culprit food (in quantities up to a normal dose for age) during oral immunotherapy. This is a reversible or partially reversible clinical response that depends on continued exposure to the allergen. If the administration of the allergen is interrupted, the previous level of clinical reactivity may return. Tolerance corresponds to the absence of adverse reactions following the ingestion of the culprit food despite a period of absence of exposure.

Conditions

FPIES

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

DOPA group

Children affected by acute persistent FPIES subjected to OIT for the offending food

Group Type: EXPERIMENTAL

Oral immunotherapy (OIT)

Intervention Type: PROCEDURE

OIT in DOPA group will be implemented as follows. Both the first micro-dose of the offending food and the subsequent micro-increments will be administered at home. Any interruptions and resumptions of OIT, due to intercurrent events (e.g. infections), will be managed via email with or without medical visit via video call. Patients will be provided with ondansetron (sublingual film) and instructions for its use. An explanatory letter will also be provided in case of need for emergency room access.

Diet group

Children affected by acute persistent FPIES subjected to the traditional measure, i.e. the elimination diet for the offending food

Group Type: ACTIVE_COMPARATOR

Culprit food elimination diet

Intervention Type: DIETARY_SUPPLEMENT

The Diet group consists of a population of children affected by acute persistent FPIES subjected to the traditional measure, i.e. the elimination diet of the incriminated food.

Interventions

Oral immunotherapy (OIT)

OIT in DOPA group will be implemented as follows. Both the first micro-dose of the offending food and the subsequent micro-increments will be administered at home. Any interruptions and resumptions of OIT, due to intercurrent events (e.g. infections), will be managed via email with or without medical visit via video call. Patients will be provided with ondansetron (sublingual film) and instructions for its use. An explanatory letter will also be provided in case of need for emergency room access.

Intervention Type: PROCEDURE

Culprit food elimination diet

The Diet group consists of a population of children affected by acute persistent FPIES subjected to the traditional measure, i.e. the elimination diet of the incriminated food.

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

Inclusion Criteria

• Pediatric patients (under 18 years of age) affected by persistent acute food protein-induced enterocolitis syndrome.
• The last anamnestic acute episode must not be more than 1 month prior to the date of inclusion in the study. The anamnestic definition of acute episode will be based on the use of Miceli Sopo 2022 questionnaire for food protein-induced enterocolitis syndrome. In case it is not clear whether the disease is active or not, an oral food challenge will be performed to verify the possible acquisition of tolerance (a procedure that is part of the routine management for this allergy). Inclusion in the study must occur within 1 month of the possible failure of the aforementioned oral food challenge. Regarding patients with multiple FPIES (expected to be approximately 6% of the total patients included, a small minority), OIT will be started for the nutritionally most relevant food among those eligible.

• Transition from acute FPIES to IgE-mediated AA.
• Absence of informed consent approval by their caregivers.
• Failure to use email by their caregivers.

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stefano Miceli Sopo

Role: PRINCIPAL_INVESTIGATOR

Fondazione Policlinico Universitario A. Gemelli, IRCCS

Locations

Fondazione Policlinico Universitario A. Gemelli IRCCS, UOC Pediatria

Roma, , Italy

Countries

Italy

Central Contacts

Stefano Miceli Sopo

Role: CONTACT

Stefano.MiceliSopo@unicatt.it

+390630155701

Facility Contacts

Stefano Miceli Sopo

Role: primary

stefano.micelisopo@policlinicogemelli.it

+393383782310

Francesco Mastellone

Role: backup

francesco.mastellone@guest.policlinicogemelli.it

Other Identifiers

6563

Identifier Type: -

Identifier Source: org_study_id