A Food Additive Removal Diet for Pediatric Eosinophilic Esophagitis (FREE)

February 6, 2025 updated by: Edward Mougey, Nemours Children's Clinic
Prospective, pragmatic standard of care clinical trial comparing dietary therapies of standard dairy elimination diet alone (DED) to dairy elimination plus food additive elimination (FREE)

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder of the esophagus. Primary symptoms manifest while eating and include dysphagia, chest pain, and food impaction. EoE was first described in the 1990s, but is increasingly recognized worldwide. It affects both adults and children.

Given that EoE is thought to be an allergen driven disease, elimination diets are considered logical and safe first-line treatment options. Elimination diets focus on the removal of the food groups most likely to evoke the inflammatory response (e.g. dairy, wheat, soy, egg, etc.). This is the first study to examine the effects of an additive free diet on eosinophilic esophagitis.

Primary Objective: To compare histologic outcomes (eosinophils per high power field: eos/hpf) of DED and FREE in children with eosinophilic esophagitis.

Secondary Objective: To compare endoscopic outcomes (Eosinophilic Esophagitis Endoscopic Reference scores: EREFs) of DED and FREE in children with eosinophilic esophagitis

Tertiary Objectives: To compare symptomatic (Pediatric Eosinophilic Esophagitis Symptom Severity Module v2.0: PEESS) and quality of life (Peds-QL EoE Module 1) outcomes of DED and FREE in children with eosinophilic esophagitis

The investigators plan to enroll 72 patients over 4 sites each enrolling 18 patients per site in a 16-month period (approximately 1 patient per month per site) having 9 patients per site in each group (DED and FREE).

The investigators will enroll patients > 5- <17 years of age with isolated esophageal eosinophilia (>15 eos/hpf). Patients with food impaction, peripheral eosinophilia > 1,500 µL , concomitant GI inflammatory conditions, history of upper GI tract surgery (e.g. fundoplication), acid reflux by pH probe, anaphylactic food allergies, severe developmental delay, taking recently prescribed inhaled corticosteroids or oral corticosteroids, have other medical conditions likely interfere with the study, has a significant psychiatric condition, has taken a PPI in the last 4 weeks, has taken swallowed steroids in the last 12 weeks, or are not fluent in spoken and written English will be excluded.

Participants will be enrolled at: Nemours Children's Hospital, Orlando, FL; Alfred I Dupont Hospital, Wilmington, DE; Seattle Children's Hospital, Seattle, WA

Once eligibility criteria are met, participants will be randomized to DED or FREE study groups. Participants will receive dietary education. Lead dietitians from each site will be identified and the approaches to dietary education will be standardized. Dietary education will be completed at the baseline visit and during follow up phone calls throughout the study.Each participant will complete all study visits in 12 weeks.

Study Type

Interventional

Enrollment (Actual)

22

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Delaware
      • Wilmington, Delaware, United States, 19083
        • Nemours/Alfred I duPont Hospital for Children
    • Florida
      • Orlando, Florida, United States, 32827
        • Nemours Children's Hospital
    • Washington
      • Seattle, Washington, United States, 98105
        • Seattle Children's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years to 18 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. An Institutional Review Board (IRB) approved written Parental Permission form is signed and dated by the parent or legal representative/caregiver.
  2. If applicable, an Institutional Review Board (IRB) approved written Assent form is signed and dated by the participant.
  3. The participant/parent(s) or legal representative(s)/caregiver(s) are considered reliable and capable of adhering to the protocol call schedule and dietary requirements.
  4. The participant is >2 years to <18 years of age.
  5. The participant has isolated esophageal eosinophilia (>15 eos/hpf).
  6. The family has access to the internet to complete weekly surveys and to a telephone to complete weekly follow up calls.
  7. The biopsy used to diagnose eosinophilic esophagitis was taken no more than 12 weeks prior to the date of enrollment.

Exclusion Criteria:

  1. The participant has peripheral eosinophilia > 1,500 µL
  2. The participant has concomitant GI inflammatory conditions (e.g. celiac disease, inflammatory bowel disease).
  3. The participant has a history of upper GI tract surgery (e.g. fundoplication)
  4. Acid reflux by pH probe is suggested (*A pH probe is not required, but may be done as standard of care)
  5. The participant has severe developmental delay that, in the opinion of the investigator, could jeopardize the participant's ability to participate in the study.
  6. The participant has taken prednisone in the last 12 weeks, or has taken fluticasone or budesonide in the last 8 weeks.
  7. The participant has other significant medical conditions that, in the opinion of the provider, would impact the participant's ability to participate in the study.
  8. The participant has a psychiatric condition that, in the opinion of the investigator, could jeopardize the participant's ability to participate in the study.
  9. The participant does not speak or read English fluently.
  10. The participant is currently taking a PPI (If discontinued, no washout required.)
  11. The participant is currently on or previously failed a dairy free diet for EoE.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: DED
Diet eliminating dairy
Other: DED
DED: Diet eliminating dairy
Active Comparator: FREE
Diet eliminating dairy and food additives
Other: FREE
FREE: Diet eliminating dairy and food additives

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Eosinophils Per High Power Field (eos/hpf)
Time Frame: 12 weeks
Histologic change differences of maximum eosinophils per high power field
12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Eosinophilic Esophagitis Endoscopic Reference Score (EREFS)
Time Frame: 12 weeks
An endoscopic outcome measure to follow response to treatment. Scores range from 0 to 15 with higher scores indicating more endoscopic evidence of eosinophilic esophagitis.
12 weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pediatric Eosinophilic Esophagitis Symptom Severity Module (PEESS)
Time Frame: Baseline, 4, 8, and 12 weeks
Self report measure of symptoms associated with eosinophilic esophagitis. Scores range from 0 to 100. The higher the score, the more frequent and severe the symptoms.
Baseline, 4, 8, and 12 weeks
Pediatric Eosinophilic Esophagitis Symptom Severity Module (PEESS): Parent Report
Time Frame: Baseline, 4, 8, and 12 weeks
Parent report measure of symptoms associated with eosinophilic esophagitis. Scores range from 0 to 100. The higher the score, the more frequent and severe the symptoms.
Baseline, 4, 8, and 12 weeks
Pediatric Quality of Life Inventory: Eosinophilic Esophagitis Module (PedsQL-EoE)
Time Frame: Baseline, 4, 8, and 12 weeks
Self report measure of quality of life and symptoms associated with eosinophilic esophagitis. This measure has several subscales (Symptoms I, Symptoms II, Treatment, Worry, Communication, Food and Eating, Food Feelings) that produce scaled scores ranging from 0 to 100. The total scaled score also ranges from 0 to 100. A higher score indicates better quality of life.
Baseline, 4, 8, and 12 weeks
Pediatric Quality of Life Inventory: Eosinophilic Esophagitis Module (PedsQL-EoE): Parent Report
Time Frame: Baseline, 4, 8, and 12 weeks
Parent report measure of quality of life and symptoms associated with eosinophilic esophagitis. This measure has several subscales (Symptoms I, Symptoms II, Treatment, Worry, Communication, Food and Eating, Food Feelings) that produce scaled scores ranging from 0 to 100. The total scaled score also ranges from 0 to 100. A higher score indicates better quality of life
Baseline, 4, 8, and 12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Nemours Children's Clinic

Investigators

  • Principal Investigator: Edward B. Mougey, PhD, Nemours Children's Clinic

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 12, 2018

Primary Completion (Actual)

December 31, 2022

Study Completion (Actual)

December 31, 2023

Study Registration Dates

First Submitted

August 31, 2018

First Submitted That Met QC Criteria

August 31, 2018

First Posted (Actual)

September 5, 2018

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

February 6, 2025

Last Verified

February 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1173700

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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