SOFEED: Six Food vs. One Food Eosinophilic Esophagitis Diet Study (SOFEED)

Six Food vs One Food Eosinophilic Esophagitis Elimination Diet (SOFEED) Followed by Swallowed Glucocorticoid Trial

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 6-food elimination diet (6FED, milk, egg, wheat, soy, tree nut/peanuts, and fish/shellfish). The study will also test the effectiveness of swallowed glucocorticoid therapy in some of the study participants for whom diet therapy was not effective.

Study Overview

• Status: Completed
• Conditions: Eosinophilic Esophagitis (EoE); Eosinophilic Gastrointestinal Disorders (EGIDs)
• Intervention / Treatment: Other: 1 Food Elimination Diet Therapy; Other: 6 Food Elimination Diet Therapy; Other: 6 Food Elimination Diet (after 1FED failure); Drug: Fluticasone Propionate, 880 mcg twice daily (after 6FED failure)

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 6FED. Participants will remain on the assigned dietary therapy for 6 weeks. At the end of 6 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 have the option to continue into Phase 2 of the study. During Phase 2, participants who were on 1FED in Phase 1 will receive 6FED therapy for 6 weeks, and participants who were on 6FED during Phase 1 will receive swallowed glucocorticoid (SGC) therapy for 6 weeks. At the end of 6 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 Type: Interventional
• Enrollment (Actual): 129
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92093
      • University of California, San Diego
  • Illinois
    • Chicago, Illinois, United States, 60208
      • Northwestern University
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts University
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina, Chapel Hill
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 56 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Have diagnosis of EoE (based on consensus criteria)
• Have histologically confirmed active disease >15 eosinophils/hpf in either distal or proximal esophagus within 12 weeks of screening visit
• Symptomatic (have experienced symptoms within the last month prior to enrollment)
• Proton pump inhibitor (PPI) confirmation
• Have a negative urine pregnancy test at screening if of childbearing potential

Exclusion Criteria:

• Have been treated with topical swallowed steroids within the last 2 months or systemic steroids within the last 3 months
• Have pathological eosinophilia in segments of the GI tract other than the esophagus determined by local review
• Have been diagnosed with a GI malabsorption disorder (i.e., Inflammatory bowel disease, Crohn's disease) or Celiac disease
• Are currently on dietary therapy strictly avoiding milk or on a 6FED
• Have concurrent H pylori gastritis or parasitic infection
• Have history of anaphylaxis to milk (with current avoidance of milk)
• Have previously failed strict dietary therapy clearly documented with one of these regimens or topical steroid treatment (i.e. have achieved histological remission of <15 eos/hpf after having been on fluticasone or >1mg budesonide per day).
• Use of investigational drugs within 4 weeks (one month) prior to enrollment
• Are concurrently receiving any of the prohibited medications for the study
• On immunotherapy for pollen (if not on maintenance therapy) or immunoglobulin-E (IgE) -mediated food allergy
• Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1-Food Elimination Diet (1FED); Participants eliminate milk from the diet in Phase 1	Other: 1 Food Elimination Diet Therapy
Active Comparator: 6-Food Elimination Diet (6FED); Participants eliminate milk, egg, wheat, soy, nuts, fish from the diet in Phase 1	Other: 6 Food Elimination Diet Therapy
Other: 1FED Non-Responders (6FED); Participants that fail to respond to 1FED in Phase 1 eliminate milk, egg, wheat, soy, nuts, fish from the diet in Phase 2	Other: 6 Food Elimination Diet (after 1FED failure)
Other: 6FED Non-responders (SGC); Participants that fail to respond to 6FED in Phase 1 administer swallowed glucocorticoids (SGC) (Flovent HFA) 880 mcg twice daily in Phase 2	Drug: Fluticasone Propionate, 880 mcg twice daily (after 6FED failure); Other Names: Flovent HFA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of Participants in Histologic Remission (<15 Eos/Hpf)	Percent of participants in histologic remission in 1FED versus 6FED groups. Remission is defined as esophageal peak eosinophil count < 15 eosinophils per high powered field (eos/hpf)	6 weeks after starting treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of Participants in Complete and Partial Histologic Remission	Percent of participants in complete and partial histologic remission in 1FED versus 6FED groups. Complete remission is defined as esophageal peak eosinophil count ≤ 1 eosinophils per high powered field (eos/hpf). Partial remission is defined as esophageal peak eosinophil count of 2 - 14 eos/hpf.	6 weeks after starting treatment
Percent of Participants Following SGC in Histologic Remission in Phase 2	Percent of participants who failed 6FED in Phase 1 in histologic remission after following swallowed glucocorticoids (SGC) in Phase 2. Remission is defined as esophageal peak eosinophil count < 15 eos/hpf	6 weeks after starting treatment
Percent of Participants Following 6FED in Histologic Remission in Phase 2	Percent of participants who failed 1FED in Phase 1 in histologic remission after following 6FED in Phase 2. Remission is defined as esophageal peak eosinophil count < 15 eos/hpf	6 weeks after starting treatment
Change From Baseline in Peak Eosinophil Count	Peak eosinophil counts were obtained at baseline and 6 weeks. The maximum (highest) peak eosinophil count among distal, mid, and proximal esophageal biopsies was obtained. Change in peak eosinophil count is defined as peak count at 6 weeks minus peak count at baseline. Changes in peak count are compared between 1FED and 6FED. A reduction (negative change) in peak count indicates improvement.	6 weeks after starting treatment
Change From Baseline in Total Histology Scoring System	The histology scoring system (HSS) measures the severity (grade) and extent (stage) of eight histologic abnormalities in the esophagus including eosinophilic inflammation, eosinophilic abscess, eosinophilic surface layering, surface epithelial alteration, dilated intercellular spaces, basal zone hyperplasia, dyskeratotic epithelial cells, and lamina propria fibrosis. Total score is the sum of grade and stage scores from the esophageal biopsy (distal, mid, or proximal) with the highest score (worst abnormalities) divided by the maximum possible score for the biopsy. Total scores range from 0 - 2 (higher scores indicate more severe and/or extensive abnormalities). Histology scores were obtained at baseline and 6 weeks. Change in total histology scoring system (HSS) is defined as total HSS score at 6 weeks minus total HSS score at baseline. Changes in scores are compared between 1FED and 6FED. A reduction (negative change) in score indicates improvement.	6 weeks after starting treatment
Change From Baseline in Total Endoscopic Reference Score	The endoscopic reference score (EREFS) utilizes standardized criteria for the presence and degree of 5 major endoscopic features (edema, fixed rings, exudates, furrows, strictures). Total score is the sum of the five feature scores from the distal and proximal esophagus. Total scores range from 0 - 18 (higher scores indicate worsening features). Endoscopic features were assessed at baseline and 6 weeks. Change in total endoscopic reference score is defined as total score at 6 weeks minus total score at baseline. Changes in scores are compared between 1FED and 6FED. A reduction (negative change) in score indicates improvement.	6 weeks after starting treatment

Collaborators and Investigators

• Sponsor: Children's Hospital Medical Center, Cincinnati
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID); National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National Center for Advancing Translational Sciences (NCATS); Office of Rare Diseases (ORD)
• Investigators: Principal Investigator: Marc E Rothenberg, MD, PhD, Children's Hospital Medical Center, Cincinnati

Publications and helpful links

Helpful Links

• Consortium of Eosinophilic Gastrointestinal Disease Researchers

Study record dates

Study Major Dates

• Study Start (Actual): May 20, 2016
• Primary Completion (Actual): April 17, 2019
• Study Completion (Actual): May 29, 2019

Study Registration Dates

• First Submitted: October 12, 2015
• First Submitted That Met QC Criteria: May 18, 2016
• First Posted (Estimate): May 20, 2016

Study Record Updates

• Last Update Posted (Actual): May 26, 2020
• Last Update Submitted That Met QC Criteria: May 18, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Hypersensitivity, Immediate; Hematologic Diseases; Gastroenteritis; Hypersensitivity; Esophageal Diseases; Leukocyte Disorders; Eosinophilia; Gastrointestinal Diseases; Digestive System Diseases; Eosinophilic Esophagitis; Esophagitis; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Dermatologic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Fluticasone; Xhance
• Other Study ID Numbers: 2015-1949; U54AI117804 (U.S. NIH Grant/Contract)