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

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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:
Collaborator:
Patient-Centered Outcomes Research Institute
Information provided by (Responsible Party):
Children's Hospital Medical Center, Cincinnati

Tracking Information
First Submitted Date  ICMJE October 12, 2015
First Posted Date  ICMJE November 20, 2015
Results First Submitted Date  ICMJE June 7, 2018
Results First Posted Date  ICMJE July 18, 2018
Last Update Posted Date August 27, 2018
Actual Study Start Date  ICMJE March 21, 2016
Actual Primary Completion Date May 16, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 27, 2018)
  • 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.
  • 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).
Original Primary Outcome Measures  ICMJE
 (submitted: November 18, 2015)
Change in Pediatric EoE Symptom Score (PEESS, version 2) from pre-treatment to post-treatment. [ Time Frame: 12 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 27, 2018)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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).
Original Secondary Outcome Measures  ICMJE
 (submitted: November 18, 2015)
  • Rate of histologic remission following 1FED or 4FED therapy (Phase 1). [ Time Frame: 12 weeks ]
  • Rate of remission following swallowed glucocorticoid therapy in the 4FED diet non-responders (Phase 2). [ Time Frame: 12 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Eosinophilic Esophagitis Intervention Trial-1 Food vs. 4 Food Elimination Diet Followed by Swallowed Glucocorticoids
Official Title  ICMJE Eosinophilic Esophagitis (EoE) Intervention Trial-Randomized 1 Food Elimination vs. 4 Food Elimination Diet Followed by Swallowed Glucocorticoids
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Eosinophilic Esophagitis
  • Eosinophilic Gastrointestinal Disorders (EGIDs)
Intervention  ICMJE
  • Other: 1 Food Elimination Diet
    Participants eliminate milk from the diet for 12 weeks
    Other Name: 1FED
  • Other: 4 Food Elimination Diet
    Participants eliminate milk, egg, wheat, soy from the diet for 12 weeks
    Other Name: 4FED
  • 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
  • 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
Study Arms  ICMJE
  • Active Comparator: 1FED
    1-food elimination diet: Participants eliminate milk from the diet in Phase 1
    Intervention: Other: 1 Food Elimination Diet
  • Active Comparator: 4FED
    4-food elimination diet: Participants eliminate milk, egg, wheat, soy from the diet in Phase 1
    Intervention: Other: 4 Food Elimination Diet
  • 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
    Intervention: Other: 4 Food Elimination Diet (post 1FED failure)
  • 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
    Intervention: Drug: Fluticasone Propionate, 800 mcg twice daily (post 4FED failure)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 22, 2018)
67
Original Estimated Enrollment  ICMJE
 (submitted: November 18, 2015)
292
Actual Study Completion Date  ICMJE May 16, 2018
Actual Primary Completion Date May 16, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Years to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02610816
Other Study ID Numbers  ICMJE 2015-2187
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
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
Supporting Materials: 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.
Responsible Party Children's Hospital Medical Center, Cincinnati
Study Sponsor  ICMJE Children's Hospital Medical Center, Cincinnati
Collaborators  ICMJE Patient-Centered Outcomes Research Institute
Investigators  ICMJE
Principal Investigator: Marc E Rothenberg, MD, PhD Children's Hospital Medical Center, Cincinnati
PRS Account Children's Hospital Medical Center, Cincinnati
Verification Date July 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP