Back to resultsEosinophilic Esophagitis Intervention Trial-1 Food vs. 4 Food Elimination Diet Followed by Swallowed Glucocorticoids
Primary Purpose
Eosinophilic Esophagitis, Eosinophilic Gastrointestinal Disorders (EGIDs)
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
1 Food Elimination Diet
4 Food Elimination Diet
4 Food Elimination Diet (post 1FED failure)
Fluticasone Propionate, 800 mcg twice daily (post 4FED failure)
Sponsored by
About this trial
This is an interventional treatment trial for Eosinophilic Esophagitis
Eligibility 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.
Sites / Locations
- Cincinnati Children's Hospital Medical Center
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Active Comparator
Active Comparator
Other
Other
Arm Label
1FED
4FED
1FED Non-Responders (4FED)
4FED Non-Responders (SGC)
Arm Description
1-food elimination diet: Participants eliminate milk from the diet in Phase 1
4-food elimination diet: Participants eliminate milk, egg, wheat, soy from the diet in Phase 1
Participants that fail to respond to 1FED in Phase 1 eliminate milk, egg, wheat, soy from the diet in Phase 2
Participants that fail to respond to 4FED in Phase 1 administer swallowed glucocorticosteroids (Flovent HFA) 800 mcg twice daily in Phase 2
Outcomes
Primary Outcome Measures
Change From Baseline in Pediatric EoE Symptom Score Version 2.0 (PEESS V2.0) at 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.
Within-group Comparisons (Baseline v. Week 12) of PEESS V2.0 Scores
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
Percent of Participants in Histologic Remission (<15 Eosinophils Per High Power Field) at 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.
Percent of Participants on Swallowed Glucocorticoids (SGC) in Histologic Remission (<15 Eos/Hpf) at 12 Weeks in Phase 2
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.
Percent of 1FED Non-responders on 4FED in Histologic Remission (<15 Eos/Hpf) at 12 Weeks in Phase 2
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.
Change From Baseline in Pediatric Quality of Life Inventory Version 3.0 EoE Module (PedsQL 3.0 EoE) at 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.
Change From Baseline in Pediatric Quality of Life Inventory Version 4.0 (PedsQL 4.0) Generic Core Scales at 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.
Change From Baseline in Endoscopic Reference Score at 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.
Percent of Participants With Positive and Negative Milk Skin Prick Tests Responding to 1FED
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).
Full Information
NCT ID
NCT02610816
First Posted
October 12, 2015
Last Updated
July 27, 2018
Sponsor
Children's Hospital Medical Center, Cincinnati
Collaborators
Patient-Centered Outcomes Research Institute
1. Study Identification
Unique Protocol Identification Number
NCT02610816
Brief Title
Eosinophilic Esophagitis Intervention Trial-1 Food vs. 4 Food Elimination Diet Followed by Swallowed Glucocorticoids
Official Title
Eosinophilic Esophagitis (EoE) Intervention Trial-Randomized 1 Food Elimination vs. 4 Food Elimination Diet Followed by Swallowed Glucocorticoids
Study Type
Interventional
2. Study Status
Record Verification Date
July 2018
Overall Recruitment Status
Completed
Study Start Date
March 21, 2016 (Actual)
Primary Completion Date
May 16, 2018 (Actual)
Study Completion Date
May 16, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Children's Hospital Medical Center, Cincinnati
Collaborators
Patient-Centered Outcomes Research Institute
4. Oversight
Data Monitoring Committee
Yes
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Eosinophilic Esophagitis, Eosinophilic Gastrointestinal Disorders (EGIDs)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
67 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1FED
Arm Type
Active Comparator
Arm Description
1-food elimination diet: Participants eliminate milk from the diet in Phase 1
Arm Title
4FED
Arm Type
Active Comparator
Arm Description
4-food elimination diet: Participants eliminate milk, egg, wheat, soy from the diet in Phase 1
Arm Title
1FED Non-Responders (4FED)
Arm Type
Other
Arm Description
Participants that fail to respond to 1FED in Phase 1 eliminate milk, egg, wheat, soy from the diet in Phase 2
Arm Title
4FED Non-Responders (SGC)
Arm Type
Other
Arm Description
Participants that fail to respond to 4FED in Phase 1 administer swallowed glucocorticosteroids (Flovent HFA) 800 mcg twice daily in Phase 2
Intervention Type
Other
Intervention Name(s)
1 Food Elimination Diet
Other Intervention Name(s)
1FED
Intervention Description
Participants eliminate milk from the diet for 12 weeks
Intervention Type
Other
Intervention Name(s)
4 Food Elimination Diet
Other Intervention Name(s)
4FED
Intervention Description
Participants eliminate milk, egg, wheat, soy from the diet for 12 weeks
Intervention Type
Other
Intervention Name(s)
4 Food Elimination Diet (post 1FED failure)
Intervention Description
Participants that fail to respond to 1FED in phase 1 eliminate milk, egg, wheat, soy from the diet for 12 weeks in Phase 2
Intervention Type
Drug
Intervention Name(s)
Fluticasone Propionate, 800 mcg twice daily (post 4FED failure)
Intervention Description
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
Primary Outcome Measure Information:
Title
Change From Baseline in Pediatric EoE Symptom Score Version 2.0 (PEESS V2.0) at 12 Weeks
Description
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.
Time Frame
Baseline and 12 weeks
Title
Within-group Comparisons (Baseline v. Week 12) of PEESS V2.0 Scores
Description
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).
Time Frame
Baseline and 12 weeks
Secondary Outcome Measure Information:
Title
Percent of Participants in Histologic Remission (<15 Eosinophils Per High Power Field) at 12 Weeks
Description
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.
Time Frame
12 weeks
Title
Percent of Participants on Swallowed Glucocorticoids (SGC) in Histologic Remission (<15 Eos/Hpf) at 12 Weeks in Phase 2
Description
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.
Time Frame
12 weeks
Title
Percent of 1FED Non-responders on 4FED in Histologic Remission (<15 Eos/Hpf) at 12 Weeks in Phase 2
Description
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.
Time Frame
12 weeks
Title
Change From Baseline in Pediatric Quality of Life Inventory Version 3.0 EoE Module (PedsQL 3.0 EoE) at 12 Weeks
Description
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.
Time Frame
Baseline and 12 weeks
Title
Change From Baseline in Pediatric Quality of Life Inventory Version 4.0 (PedsQL 4.0) Generic Core Scales at 12 Weeks
Description
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.
Time Frame
Baseline and 12 weeks
Title
Change From Baseline in Endoscopic Reference Score at 12 Weeks
Description
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.
Time Frame
Baseline and 12 weeks
Title
Percent of Participants With Positive and Negative Milk Skin Prick Tests Responding to 1FED
Description
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).
Time Frame
Baseline and 12 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marc E Rothenberg, MD, PhD
Organizational Affiliation
Children's Hospital Medical Center, Cincinnati
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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.
IPD Sharing Time Frame
After the associated research findings have been published, data will be made available for research purposes
IPD Sharing 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.
Learn more about this trial
Eosinophilic Esophagitis Intervention Trial-1 Food vs. 4 Food Elimination Diet Followed by Swallowed Glucocorticoids
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