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Trial record 1 of 1 for:    NCT02610816
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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

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Eosinophilic Esophagitis
Eosinophilic Gastrointestinal Disorders (EGIDs)
Interventions 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)
Enrollment 67
Recruitment Details Participants were recruited from eosinophilic esophagitis (EoE) specialty clinics (10 sites) in the USA between November 2015 and February 2018.
Pre-assignment Details 67 participants screened, 4 excluded (2 did not meet inclusion criteria, 2 met exclusion criteria), and 63 randomized
Arm/Group Title 1FED 4FED 1FED Non-responders (4FED) 4FED Non-responders (SGC)
Hide Arm/Group Description 1-food elimination diet: participants eliminate milk from the diet for 12 weeks 4-food elimination diet: participants eliminate milk, egg, wheat, soy from the diet for 12 weeks Participants that fail to respond to 1FED in phase 1 eliminate milk, egg, wheat, soy from the diet for 12 weeks in phase 2 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
Period Title: Phase 1
Started 38 25 0 0
Completed 34 17 0 0
Not Completed 4 8 0 0
Reason Not Completed
Withdrawal by Subject             2             6             0             0
Lost to Follow-up             2             1             0             0
Physician Decision             0             1             0             0
Period Title: Phase 2
Started 0 0 19 10
Completed 0 0 8 4
Not Completed 0 0 11 6
Reason Not Completed
Withdrawal by Subject             0             0             9             3
Lost to Follow-up             0             0             2             0
Physician Decision             0             0             0             2
Pregnancy             0             0             0             1
Arm/Group Title 1FED 4FED Total
Hide Arm/Group Description 1-food elimination diet: participants eliminate milk from the diet for 12 weeks 4-food elimination diet: participants eliminate milk, egg, wheat, soy from the diet for 12 weeks Total of all reporting groups
Overall Number of Baseline Participants 38 25 63
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 38 participants 25 participants 63 participants
12.3  (3.1) 12.1  (3.7) 12.2  (3.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 38 participants 25 participants 63 participants
Female
12
  31.6%
9
  36.0%
21
  33.3%
Male
26
  68.4%
16
  64.0%
42
  66.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 38 participants 25 participants 63 participants
Hispanic or Latino
4
  10.5%
3
  12.0%
7
  11.1%
Not Hispanic or Latino
33
  86.8%
21
  84.0%
54
  85.7%
Unknown or Not Reported
1
   2.6%
1
   4.0%
2
   3.2%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 38 participants 25 participants 63 participants
White
33
  86.8%
22
  88.0%
55
  87.3%
Black or African American
4
  10.5%
1
   4.0%
5
   7.9%
Other
1
   2.6%
2
   8.0%
3
   4.8%
Atopy  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 38 participants 25 participants 63 participants
Atopic
34
  89.5%
19
  76.0%
53
  84.1%
Not Atopic
4
  10.5%
6
  24.0%
10
  15.9%
1.Primary Outcome
Title Change From Baseline in Pediatric EoE Symptom Score Version 2.0 (PEESS V2.0) at 12 Weeks
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
We performed intent to treat analysis including participants who had at least one clinical observation post randomization.
Arm/Group Title 1FED 4FED
Hide Arm/Group Description:
1-food elimination diet: participants eliminate milk from the diet for 12 weeks
4-food elimination diet: participants eliminate milk, egg, wheat, soy from the diet for 12 weeks
Overall Number of Participants Analyzed 33 16
Mean (Standard Deviation)
Unit of Measure: units on a scale
-14.3  (17.1) -21.6  (17.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1FED, 4FED
Comments The primary treatment comparison was to compare change in PEESS V2.0 scores of 1FED versus 4FED. The primary null hypothesis was 4FED would be no more effective than 1FED. This was designed as a superiority trial.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.04
Comments P-values are not adjusted for multiplicity, since a single primary endpoint is analyzed
Method Mixed Models Analysis
Comments No adjustment of degrees of freedom is needed.
2.Primary Outcome
Title Within-group Comparisons (Baseline v. Week 12) of PEESS V2.0 Scores
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
We performed intent to treat analysis including participants who had at least one clinical observation post randomization
Arm/Group Title 1FED 4FED
Hide Arm/Group Description:
1-food elimination diet: participants eliminate milk from the diet for 12 weeks
4-food elimination diet: participants eliminate milk, egg, wheat, soy from the diet for 12 weeks
Overall Number of Participants Analyzed 38 24
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline - Total Score Number Analyzed 38 participants 24 participants
38.1  (14.2) 42.9  (16.0)
Week 12 - Total Score Number Analyzed 33 participants 17 participants
23.5  (18.3) 16.0  (13.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1FED
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments This is a calculated p-value. The threshold for statistical significance is p <0.05.
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 4FED
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments This is a calculated p-value. The threshold for statistical significance is p <0.05
Method Mixed Models Analysis
Comments [Not Specified]
3.Secondary Outcome
Title Percent of Participants in Histologic Remission (<15 Eosinophils Per High Power Field) at 12 Weeks
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
We performed intent to treat analysis including participants who had at least one clinical observation post randomization.
Arm/Group Title 1FED 4FED
Hide Arm/Group Description:
1-food elimination diet: participants eliminate milk from the diet for 12 weeks
4-food elimination diet: participants eliminate milk, egg, wheat, soy from the diet for 12 weeks
Overall Number of Participants Analyzed 34 17
Measure Type: Number
Unit of Measure: percentage of participants
Complete remission (≤ 1 eos/hpf) 20.6 17.6
Partial remission (2 - 14 eos/hpf) 23.5 23.5
Remission (< 15 eos/hpf) 44.1 41.2
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1FED, 4FED
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
4.Secondary Outcome
Title Percent of Participants on Swallowed Glucocorticoids (SGC) in Histologic Remission (<15 Eos/Hpf) at 12 Weeks in Phase 2
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
We performed intent to treat analysis including participants who had at least one clinical observation post randomization
Arm/Group Title 4FED Non-responders (SGC)
Hide Arm/Group 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
Overall Number of Participants Analyzed 4
Measure Type: Number
Unit of Measure: percentage of participants
Complete remission (≤ 1 eos/hpf) 25.0
Partial remission (2 - 14 eos/hpf) 25.0
Remission (< 15 eos/hpf) 50.0
5.Secondary Outcome
Title Percent of 1FED Non-responders on 4FED in Histologic Remission (<15 Eos/Hpf) at 12 Weeks in Phase 2
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
We performed Intent to treat analysis including participants who had at least one clinical observation post randomization.
Arm/Group Title 1FED Non-responders (4FED)
Hide Arm/Group 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
Overall Number of Participants Analyzed 8
Measure Type: Number
Unit of Measure: percentage of participants
Complete remission (≤ 1 eos/hpf) 0
Partial remission (2 - 14 eos/hpf) 12.5
Remission (< 15 eos/hpf) 12.5
6.Secondary Outcome
Title Change From Baseline in Pediatric Quality of Life Inventory Version 3.0 EoE Module (PedsQL 3.0 EoE) at 12 Weeks
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
We performed intent to treat analysis including participants who had at least one clinical observation post randomization
Arm/Group Title 1FED 4FED
Hide Arm/Group Description:
1-food elimination diet: participants eliminate milk from the diet for 12 weeks
4-food elimination diet: participants eliminate milk, egg, wheat, soy from the diet for 12 weeks
Overall Number of Participants Analyzed 38 25
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline - Total Score Number Analyzed 38 participants 25 participants
71.3  (13.0) 67.5  (13.6)
Change from Baseline to Week 12 Number Analyzed 31 participants 16 participants
9.7  (11.3) 9.8  (14.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1FED, 4FED
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.93
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
7.Secondary Outcome
Title Change From Baseline in Pediatric Quality of Life Inventory Version 4.0 (PedsQL 4.0) Generic Core Scales at 12 Weeks
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
We performed intent to treat analysis including participants who had at least one clinical observation post randomization
Arm/Group Title 1FED 4FED
Hide Arm/Group Description:
1-food elimination diet: participants eliminate milk from the diet for 12 weeks
4-food elimination diet: participants eliminate milk, egg, wheat, soy from the diet for 12 weeks
Overall Number of Participants Analyzed 38 24
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline - Total Score Number Analyzed 38 participants 24 participants
80.3  (10.8) 79.9  (14.5)
Change from Baseline to Week 12 Number Analyzed 33 participants 16 participants
3.7  (9.9) 5.3  (16.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1FED, 4FED
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.74
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
8.Secondary Outcome
Title Change From Baseline in Endoscopic Reference Score at 12 Weeks
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
We performed intent to treat analysis including participants who had at least one clinical observation post randomization
Arm/Group Title 1FED 4FED
Hide Arm/Group Description:
1-food elimination diet: participants eliminate milk from the diet for 12 weeks
4-food elimination diet: participants eliminate milk, egg, wheat, soy from the diet for 12 weeks
Overall Number of Participants Analyzed 22 12
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline - Total Score Number Analyzed 22 participants 12 participants
2.5  (1.3) 3.3  (1.8)
Change from Baseline to Week 12 Number Analyzed 17 participants 12 participants
-0.7  (2.2) -1.3  (2.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1FED, 4FED
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.36
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
9.Secondary Outcome
Title Percent of Participants With Positive and Negative Milk Skin Prick Tests Responding to 1FED
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
We performed intent to treat analysis including participants who had at least one clinical observation post randomization
Arm/Group Title 1FED
Hide Arm/Group Description:
1-food elimination diet: participants eliminate milk from the diet for 12 weeks
Overall Number of Participants Analyzed 28
Measure Type: Number
Unit of Measure: percentage of participants
Percent of total with positive milk SPT 11
Percent of total with negative milk SPT 89
Percent with positive SPT responding to 1FED 33
Percent with negative SPT responding to 1FED 48
Time Frame Adverse events were collected from informed consent/assent to 30 days after the cessation of the study agent (2 years, 2 months).
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title 1FED 4FED 1FED Non-responders (4FED) 4FED Non-responders (SGC)
Hide Arm/Group Description 1-food elimination diet (Phase 1) 4-food elimination diet (Phase 1) 4-food elimination diet (Phase 2) Swallowed glucocorticosteroids (Flovent HFA) (Phase 2)
All-Cause Mortality
1FED 4FED 1FED Non-responders (4FED) 4FED Non-responders (SGC)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/38 (0.00%)   0/25 (0.00%)   0/19 (0.00%)   0/10 (0.00%) 
Hide Serious Adverse Events
1FED 4FED 1FED Non-responders (4FED) 4FED Non-responders (SGC)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/38 (2.63%)   1/25 (4.00%)   0/19 (0.00%)   0/10 (0.00%) 
Gastrointestinal disorders         
Abdominal Pain  1  1/38 (2.63%)  1/25 (4.00%)  0/19 (0.00%)  0/10 (0.00%) 
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
1FED 4FED 1FED Non-responders (4FED) 4FED Non-responders (SGC)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   5/38 (13.16%)   8/25 (32.00%)   6/19 (31.58%)   6/10 (60.00%) 
Ear and labyrinth disorders         
Ear Pain  1  0/38 (0.00%)  0/25 (0.00%)  1/19 (5.26%)  0/10 (0.00%) 
Gastrointestinal disorders         
Abdominal Pain  1  2/38 (5.26%)  2/25 (8.00%)  0/19 (0.00%)  0/10 (0.00%) 
Constipation  1  0/38 (0.00%)  0/25 (0.00%)  1/19 (5.26%)  0/10 (0.00%) 
Vomiting  1  1/38 (2.63%)  2/25 (8.00%)  1/19 (5.26%)  2/10 (20.00%) 
Infections and infestations         
Otitis Media  1  0/38 (0.00%)  0/25 (0.00%)  1/19 (5.26%)  0/10 (0.00%) 
Sinusitis  1  0/38 (0.00%)  0/25 (0.00%)  0/19 (0.00%)  1/10 (10.00%) 
Nervous system disorders         
Headache  1  0/38 (0.00%)  0/25 (0.00%)  1/19 (5.26%)  0/10 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Cough  1  1/38 (2.63%)  2/25 (8.00%)  0/19 (0.00%)  1/10 (10.00%) 
Nasal Congestion  1  1/38 (2.63%)  0/25 (0.00%)  0/19 (0.00%)  1/10 (10.00%) 
Sinus Disorder  1  0/38 (0.00%)  0/25 (0.00%)  1/19 (5.26%)  1/10 (10.00%) 
Skin and subcutaneous tissue disorders         
Urticaria  1  0/38 (0.00%)  2/25 (8.00%)  0/19 (0.00%)  0/10 (0.00%) 
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Marc E. Rothenberg, MD, PhD
Organization: Cincinnati Childrens Hospital Medical Center
Phone: 513-636-7177
EMail: Marc.Rothenberg@cchmc.org
Layout table for additonal information
Responsible Party: Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier: NCT02610816    
Other Study ID Numbers: 2015-2187
First Submitted: October 12, 2015
First Posted: November 20, 2015
Results First Submitted: June 7, 2018
Results First Posted: July 18, 2018
Last Update Posted: August 27, 2018