Eosinophilic Esophagitis Intervention Trial-1 Food vs. 4 Food Elimination Diet Followed by Swallowed Glucocorticoids

• ClinicalTrials.gov Identifier: NCT02610816
• Recruitment Status: Completed
• First Posted: November 20, 2015
• Results First Posted: July 18, 2018
• Last Update Posted: August 27, 2018
• Sponsor: Children's Hospital Medical Center, Cincinnati
• Collaborator: Patient-Centered Outcomes Research Institute
• Information provided by (Responsible Party): Children's Hospital Medical Center, Cincinnati

Study Description

Brief Summary:

The purpose of this interventional study is to test and compare the effectiveness of two elimination diets-the 1-food elimination diet (1FED, milk only) and the 4-food elimination diet (4FED, milk, egg, wheat, and soy) for eosinophilic esophagitis (EoE). The study will also test the effectiveness of swallowed glucocorticoid therapy in some of the study participants for whom diet therapy was not effective.

Condition or disease	Intervention/treatment	Phase
Eosinophilic Esophagitis; Eosinophilic Gastrointestinal Disorders (EGIDs)	Other: 1 Food Elimination Diet; Other: 4 Food Elimination Diet; Other: 4 Food Elimination Diet (post 1FED failure); Drug: Fluticasone Propionate, 800 mcg twice daily (post 4FED failure)	Phase 2; Phase 3

Detailed Description:

This study will consist of two phases, plus a screening period. During the screening period, subject eligibility for the study will be determined. During Phase 1, qualified participants will be randomly assigned to one of two elimination diet therapies--the 1FED or the 4FED. Participants will remain on the assigned dietary therapy for 12 weeks. At the end of 12 weeks of therapy, esophageal biopsies from participant's standard of care (i.e. normal, routine care) endoscopy will be evaluated to determine disease status. Participants whose EoE is in remission (i.e. <15 eos/hpf) will be done with the study.

Participants whose EoE is still active (i.e. ≥15 eos/hpf) will continue into Phase 2 of the study. During Phase 2, participants who were on 1FED in Phase 1 will receive 4FED therapy for 12 weeks, and participants who were on 4FED during Phase 1 will receive swallowed glucocorticoid therapy for 12 weeks. At the end of 12 weeks of therapy, esophageal biopsies from participant's standard of care (i.e. normal, routine care) endoscopy will be evaluated to determine disease status.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 67 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Eosinophilic Esophagitis (EoE) Intervention Trial-Randomized 1 Food Elimination vs. 4 Food Elimination Diet Followed by Swallowed Glucocorticoids
• Actual Study Start Date: March 21, 2016
• Actual Primary Completion Date: May 16, 2018
• Actual Study Completion Date: May 16, 2018

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: 1FED; 1-food elimination diet: Participants eliminate milk from the diet in Phase 1	Other: 1 Food Elimination Diet; Participants eliminate milk from the diet for 12 weeks; Other Name: 1FED
Active Comparator: 4FED; 4-food elimination diet: Participants eliminate milk, egg, wheat, soy from the diet in Phase 1	Other: 4 Food Elimination Diet; Participants eliminate milk, egg, wheat, soy from the diet for 12 weeks; Other Name: 4FED
1FED Non-Responders (4FED); Participants that fail to respond to 1FED in Phase 1 eliminate milk, egg, wheat, soy from the diet in Phase 2	Other: 4 Food Elimination Diet (post 1FED failure); Participants that fail to respond to 1FED in phase 1 eliminate milk, egg, wheat, soy from the diet for 12 weeks in Phase 2
4FED Non-Responders (SGC); Participants that fail to respond to 4FED in Phase 1 administer swallowed glucocorticosteroids (Flovent HFA) 800 mcg twice daily in Phase 2	Drug: Fluticasone Propionate, 800 mcg twice daily (post 4FED failure); Participants that fail to respond to 4FED in phase 1 administer swallowed glucocorticosteroids (Flovent HFA) 800 mcg twice daily for 12 weeks in Phase 2

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in Pediatric EoE Symptom Score Version 2.0 (PEESS V2.0) at 12 Weeks [ Time Frame: Baseline and 12 weeks ]
   The PEESS V2.0 questionnaire captures EoE-specific symptoms (dysphagia, gastro-esophageal reflux disease (GERD), nausea/vomiting, and pain) as reported by children with EoE (8-18 years of age) and their parents (for children 2-18 years of age). The range for PEESS v2.0 scores is 0 to 100, with a higher score being indicative of more frequent and/or severe symptoms. Scores were obtained at baseline and 12 weeks. Change in score is defined as total score at 12 weeks minus total score at baseline. The parent-proxy PEESS total score change from pre-treatment to post-treatment is the primary efficacy endpoint. 1FED vs 4FED changes are compared. A reduction in score (negative change) is indicative of a reduction in symptoms.
2. Within-group Comparisons (Baseline v. Week 12) of PEESS V2.0 Scores [ Time Frame: Baseline and 12 weeks ]
   The PEESS V2.0 questionnaire captures EoE-specific symptoms. The range for PEESS v2.0 scores is 0 to 100, with a higher score being indicative of more frequent and/or severe symptoms. Baseline vs Week 12 scores are compared within each treatment group (1FED and 4FED).

Secondary Outcome Measures :

1. Percent of Participants in Histologic Remission (<15 Eosinophils Per High Power Field) at 12 Weeks [ Time Frame: 12 weeks ]
   Percent of participants in remission in 1FED and 4FED groups. Remission is defined as clinical esophageal peak eosinophil count < 15 eosinophils per high power field (eos/hpf). Complete remission is defined as ≤ 1 peak eos/hpf and partial remission as 2 - 14 peak eos/hpf.
2. Percent of Participants on Swallowed Glucocorticoids (SGC) in Histologic Remission (<15 Eos/Hpf) at 12 Weeks in Phase 2 [ Time Frame: 12 weeks ]
   Percent of 4FED non-responders on SGC in Phase 2 in histologic remission. Remission is defined as esophageal peak eosinophil count < 15 eosinophils per high power field (eos/hpf). Complete remission is defined as ≤ 1 peak eos/hpf and partial remission as 2 - 14 peak eos/hpf.
3. Percent of 1FED Non-responders on 4FED in Histologic Remission (<15 Eos/Hpf) at 12 Weeks in Phase 2 [ Time Frame: 12 weeks ]
   Percent of 1FED non-responders on 4FED in histologic remission in phase 2. Remission is defined as esophageal peak eosinophil count < 15 eosinophils per high powered field. Complete remission is defined as ≤ 1 peak eos/hpf and partial remission as 2 - 14 peak eos/hpf.
4. Change From Baseline in Pediatric Quality of Life Inventory Version 3.0 EoE Module (PedsQL 3.0 EoE) at 12 Weeks [ Time Frame: Baseline and 12 weeks ]
   The PedsQL 3.0 EoE measures symptoms and problems related to treatment, worry, communication, food/eating, and feelings. The range for PedsQL 3.0 EoE scores is 0 to 100, with a higher score indicating better quality of life. Scores were obtained at baseline and 12 weeks. Change in score is defined as the PedsQL 3.0 EoE total score at 12 weeks minus total score at baseline. 1FED vs 4FED changes are compared. An increase in score (positive change) is indicative of improved quality of life.
5. Change From Baseline in Pediatric Quality of Life Inventory Version 4.0 (PedsQL 4.0) Generic Core Scales at 12 Weeks [ Time Frame: Baseline and 12 weeks ]
   The PedsQL 4.0 measures physical and psychosocial function. The range for PedsQL 4.0 scores is 0 to 100, with a higher score indicating better quality of life. Scores were obtained at baseline and 12 weeks. Change in score is defined as the PedsQL 4.0 total score at 12 weeks minus total score at baseline. 1FED vs 4FED changes are compared. An increase in score (positive change) is indicative of improved quality of life.
6. Change From Baseline in Endoscopic Reference Score at 12 Weeks [ Time Frame: Baseline and 12 weeks ]
   The EoE Endoscopic Reference Score (EREFS) measures features of EoE including esophageal edema, rings, exudate, furrows, and strictures. The instrument grades edema and furrows as absent (0) or present (1); rings as absent (0), mild (1, subtle circumferential ridges), moderate (2, distinct rings) and severe (3, rings that impair passage of a standard adult diagnostic endoscope); exudates as absent (0), mild (1, less than 10% of the esophageal surface area) or severe (2, greater or equal to 10% of the esophageal surface area); and strictures as absent (0) or present (1) with an estimation of the minimal luminal diameter. Higher scores indicate more severe disease (range 0 - 9). Scores were obtained at baseline and 12 weeks. Change in score is defined as the EREFS total score at 12 weeks minus total score at baseline. 1FED vs 4FED changes are compared. A reduction in score (negative change) is indicative of a reduction in esophageal abnormalities.
7. Percent of Participants With Positive and Negative Milk Skin Prick Tests Responding to 1FED [ Time Frame: Baseline and 12 weeks ]
   Reactions to skin prick test (SPT) to milk is positive if the wheal size of the milk test is at least 3 mm larger than the wheal size of the negative control. Treatment response is defined as clinical histologic remission (<15 eos/hpf).

Eligibility Criteria

• Ages Eligible for Study: 6 Years to 17 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Have diagnosis of EoE (based on consensus criteria)
• Are aged 6 to 17 years
• Have histologically confirmed active disease >15 eosinophils/hpf in either distal or proximal esophagus within 12 weeks of screening visit
• Proton Pump Inhibitor (PPI) confirmation
• Symptomatic (have experienced symptoms within the last month prior to enrollment)
• Has a negative urine pregnancy test at screening if of childbearing potential. Females of childbearing potential must have a negative urine pregnancy test (β-hCG) prior to enrollment into the study (i.e., at screening). Subsequently, these participants must agree to use adequate birth control measures (e.g., condom, oral/injectable/subcutaneous contraceptives, intrauterine device, or sexual abstinence) during the study and for at least one month after the last dose of study drug which will be documented in the source documents.

Exclusion Criteria:

• Have been treated with topical swallowed steroids within the last 2 months or systemic steroids within the past 3 months
• Have eosinophilia in segments of the GI tract other than the esophagus
• Have been diagnosed with a GI malabsorption disorder (i.e., Inflammatory bowel disease, Crohn's disease) or Celiac disease
• Are currently on dietary therapy avoiding milk
• Have concurrent H pylori gastritis or parasitic infection
• Are unable to obtain esophagogastroduodenoscopy with esophageal biopsies at Cincinnati Children's Hospital Medical Center (CCHMC) or other participating institution within 4 weeks of study completion
• Have previously failed (in a clinical trial setting) dietary therapy with one of these regimens or topical steroid treatment with fluticasone at a total dose of 1760 mcg per day.
• Have definitely responded (in a clinical trial setting) to either dietary therapy avoiding these antigens or to swallowed fluticasone at a total dose of 1760 mcg per day
• Are concurrently receiving any of the prohibited medications listed in Table 2
• On immunotherapy for pollen (if not on maintenance therapy) or immunoglobulin E (IgE)-mediated food allergy.

Contacts and Locations

Locations

United States, Ohio

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States, 45229

Sponsors and Collaborators

Children's Hospital Medical Center, Cincinnati

Patient-Centered Outcomes Research Institute

Investigators

• Principal Investigator: Marc E Rothenberg, MD, PhD; Children's Hospital Medical Center, Cincinnati

  Study Documents (Full-Text)

Documents provided by Children's Hospital Medical Center, Cincinnati:

Study Protocol  [PDF] July 28, 2016

Statistical Analysis Plan  [PDF] March 5, 2015

More Information

• Responsible Party: Children's Hospital Medical Center, Cincinnati
• ClinicalTrials.gov Identifier: NCT02610816
• Other Study ID Numbers: 2015-2187
• First Posted: November 20, 2015
• Results First Posted: July 18, 2018
• Last Update Posted: August 27, 2018
• Last Verified: July 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: The raw anonymized data tables, data dictionaries, and study documentation will be provided to outside investigators upon request, with the proviso that it may not be linked with external datasets so as to minimize the risk of re-identification. When the resources and the associated research findings have been published, data will be made available for research purposes to qualified individuals within the scientific community. Consortium participants will retain rights to any subject inventions generated.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP)
• Time Frame: After the associated research findings have been published, data will be made available for research purposes
• Access Criteria: Data will be provided in a form suitable for a variety of databases. Data will be provided to qualified individuals within the scientific community, according to federal guidelines.

Additional relevant MeSH terms:

Esophagitis; Eosinophilic Esophagitis; Gastrointestinal Diseases; Digestive System Diseases; Esophageal Diseases; Gastroenteritis; Eosinophilia; Leukocyte Disorders; Hematologic Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Fluticasone; Xhance; Anti-Inflammatory Agents; Bronchodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Asthmatic Agents; Respiratory System Agents; Dermatologic Agents; Anti-Allergic Agents