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

• ClinicalTrials.gov Identifier: NCT02778867
• Recruitment Status: Completed
• First Posted: May 20, 2016
• Results First Posted: May 26, 2020
• Last Update Posted: May 26, 2020
• Sponsor: Children's Hospital Medical Center, Cincinnati
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National Institute of Allergy and Infectious Diseases (NIAID); Office of Rare Diseases (ORD); National Center for Advancing Translational Science (NCATS)
• 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 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.

Condition or disease	Intervention/treatment	Phase
Eosinophilic Gastrointestinal Disorders (EGIDs); Eosinophilic Esophagitis (EoE)	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)	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 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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 129 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Six Food vs One Food Eosinophilic Esophagitis Elimination Diet (SOFEED) Followed by Swallowed Glucocorticoid Trial
• Actual Study Start Date: May 20, 2016
• Actual Primary Completion Date: April 17, 2019
• Actual Study Completion Date: May 29, 2019

Arms and Interventions

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
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)
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 Name: Flovent HFA

Outcome Measures

Primary Outcome Measures :

1. Percent of Participants in Histologic Remission (<15 Eos/Hpf) [ Time Frame: 6 weeks after starting treatment ]
   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)

Secondary Outcome Measures :

1. Percent of Participants in Complete and Partial Histologic Remission [ Time Frame: 6 weeks after starting treatment ]
   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.
2. Percent of Participants Following SGC in Histologic Remission in Phase 2 [ Time Frame: 6 weeks after starting treatment ]
   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
3. Percent of Participants Following 6FED in Histologic Remission in Phase 2 [ Time Frame: 6 weeks after starting treatment ]
   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
4. Change From Baseline in Peak Eosinophil Count [ Time Frame: 6 weeks after starting treatment ]
   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.
5. Change From Baseline in Total Histology Scoring System [ Time Frame: 6 weeks after starting treatment ]
   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. Change From Baseline in Total Endoscopic Reference Score [ Time Frame: 6 weeks after starting treatment ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, California

University of California, San Diego

La Jolla, California, United States, 92093

United States, Illinois

Northwestern University

Chicago, Illinois, United States, 60208

United States, Massachusetts

Tufts University

Boston, Massachusetts, United States, 02111

United States, Minnesota

Mayo Clinic

Rochester, Minnesota, United States, 55905

United States, New York

Icahn School of Medicine at Mount Sinai

New York, New York, United States, 10029

United States, North Carolina

University of North Carolina, Chapel Hill

Chapel Hill, North Carolina, United States, 27599

United States, Ohio

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States, 45229

United States, Pennsylvania

University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

United States, Utah

University of Utah

Salt Lake City, Utah, United States, 84132

Sponsors and Collaborators

Children's Hospital Medical Center, Cincinnati

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

National Institute of Allergy and Infectious Diseases (NIAID)

Office of Rare Diseases (ORD)

National Center for Advancing Translational Science (NCATS)

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:

Informed Consent Form  [PDF] May 29, 2018

Statistical Analysis Plan  [PDF] October 14, 2019

Study Protocol  [PDF] November 22, 2017

More Information

Additional Information:

Consortium of Eosinophilic Gastrointestinal Disease Researchers 

• Responsible Party: Children's Hospital Medical Center, Cincinnati
• ClinicalTrials.gov Identifier: NCT02778867
• Other Study ID Numbers: 2015-1949; U54AI117804 ( U.S. NIH Grant/Contract )
• First Posted: May 20, 2016
• Results First Posted: May 26, 2020
• Last Update Posted: May 26, 2020
• Last Verified: May 2020

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