A Study of Flovent in Patients With Eosinophilic Esophagitis

• ClinicalTrials.gov Identifier: NCT00426283
• Recruitment Status: Completed
• First Posted: January 24, 2007
• Results First Posted: February 3, 2014
• Last Update Posted: October 19, 2020
• Sponsor: Marc Rothenberg, MD
• Information provided by (Responsible Party): Marc Rothenberg, MD, Children's Hospital Medical Center, Cincinnati

Tracking Information

• First Submitted Date: January 22, 2007
• First Posted Date: January 24, 2007
• Results First Submitted Date: December 16, 2013
• Results First Posted Date: February 3, 2014
• Last Update Posted Date: October 19, 2020
• Actual Study Start Date: January 2007
• Actual Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 24, 2020)

Percentage of Participants Who Attained Remission. [ Time Frame: 3 months ]

Remission is considered achieved when the highest eosinophil count per high power field (hpf) in all esophageal biopsies is </= 1 eosinophil/hpf after 3 months of therapy.

• Original Primary Outcome Measures (submitted: January 22, 2007): To investigate the ability of 1760mcg fluticasone propionate (FP) swallowed from a metered-dose inhaler (MDI) to induce remission of eosinophilic esophagitis (EE) (highest count of eosinophils per HPF for all esophageal biopsies to < 1 cell per HPF.

Current Secondary Outcome Measures (submitted: September 24, 2020)

• Percent of Participants With Decreased Cortisol Levels After 3 Months [ Time Frame: 3 months ]
  Blood and saliva cortisol was measured and compared to reference range at 3 months. Participants with measures below the reference range were considered "decreased".
• Association of Subject Age, Body Mass Index Z-score, and Allergic Status to Response to Flovent [ Time Frame: 3 months ]
  Strength of the association (odds ratio) of age, body mass index (BMI) z-score , and allergic status with response to Flovent. Allergic status is defined as a history of allergic disease (allergic rhinitis, hay fever, atopic dermatitis, eczema, food anaphylaxis, asthma, or positive skin prick tests). Response is defined as <= 1 eosinophil/high power field in esophageal biopsies.
• EoE Score After 3 Months [ Time Frame: 3 months ]
  The gene expression profile is associated with an EoE score algorithm reflecting disease status and severity in a quantifiable number - called the EoE score, based on a core set of 77 diagnostic genes. The EoE score was calculated for Flovent responders and placebo. Higher scores indicate normalization of genes associated with inflammation and fibrosis (disease severity). Therefore higher scores mean a better outcome. The minimum score is zero. There is no maximum score.
• Association of Compliance With Therapy and Response to Flovent [ Time Frame: 3 months ]
  Odds ratio was determined to show the strength of the association between compliance with the drug therapy and response to the drug therapy
• Percent of Participants With Abdominal Pain After Therapy [ Time Frame: 3 months ]
  Percent of participants responding that they experienced abdominal pain (i.e. they did not respond "never") after therapy. Responses were dichotomized into "Never" and "sometimes".

Original Secondary Outcome Measures (submitted: January 22, 2007)

• To Investigate the Safety of 1760mcg FP in the Treatment of EE Using Measurement of Serial Salivary Cortisol Levels and Adverse Reaction Data.
• To Investigate the Relationship Between Subject Age, Height, Weight, Allergic Status and Response to FP.
• To Investigate the Relationship Between Gene Expression, Blood Levels (CBC, Serum IL-5, Eotaxin-3 and IgE) Eosinophil Phenotype, (Via Flow Cytometry and Functional Responses) and Response to FP.
• To Investigate Subject Compliance and Response to FP.
• To Investigate the Change in Subject Symptoms and Response to FP.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Flovent in Patients With Eosinophilic Esophagitis
• Official Title: A Double Blinded, Randomized Trial of Swallowed 1760mcg Fluticasone Propionate Versus Placebo in the Treatment of Eosinophilic Esophagitis
• Brief Summary: The purpose of this study is to test the effects (both good and bad) of high dose swallowed fluticasone propionate (Flovent) in subjects with eosinophilic esophagitis (EoE).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Eosinophilic Esophagitis

Intervention

• Drug: Flovent
  1760 mcg daily
  Other Name: Fluticasone propionate
• Other: Placebo
  Placebo

Study Arms

• Experimental: Flovent 1760 mcg
  Fluticasone propionate 880 mcg twice daily for 3 months
  Intervention: Drug: Flovent
• Placebo Comparator: Placebo
  Placebo twice daily for 3 months
  Intervention: Other: Placebo

• Publications *: Butz BK, Wen T, Gleich GJ, Furuta GT, Spergel J, King E, Kramer RE, Collins MH, Stucke E, Mangeot C, Jackson WD, O'Gorman M, Abonia JP, Pentiuk S, Putnam PE, Rothenberg ME. Efficacy, dose reduction, and resistance to high-dose fluticasone in patients with eosinophilic esophagitis. Gastroenterology. 2014 Aug;147(2):324-33.e5. doi: 10.1053/j.gastro.2014.04.019. Epub 2014 Apr 22.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 16, 2013): 42
• Original Enrollment (submitted: January 22, 2007): 40
• Actual Study Completion Date: March 2012
• Actual Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Signed informed consent for study by subject, or parent/guardian if subject is a minor. Assent will be obtained from all minors 11 years of age and older.
• Histological findings on esophageal biopsy to include peak eosinophil density ≥ 24 per high power field (400x) in the proximal or distal esophagus validated by a pathologist at CCHMC.
• Allergy evaluation including skin-prick testing with multiple food antigens to ensure elimination diet is not indicated.
• Have undergone a minimum 3 months of elimination diet as indicated by skin-prick testing without detectable resolution by repeat endoscopy with biopsies demonstrating persistent EE OR subject/parental refusal to follow elimination diet. If the subject/parent refuses the elimination diet, they are eligible for this study.
• Treatment with a proton-pump inhibitor for at least two months (rounded to nearest month) prior to endoscopy OR failure of histological improvement as defined by < 1 eosinophil per HPF after 2 month (rounded to nearest month) trial of proton pump inhibitor documented by prior endoscopy. The PPI must be used prior to endoscopy to rule out the possibility of GERD.

Exclusion Criteria:

• History of poor tolerance to Fluticasone Propionate (FP), as defined as multiple episodes of oral candidiasis, hypothalamic-pituitary-adrenal axis suppression as evidenced by signs of Cushing syndrome, headaches, or increased respiratory infections during exposure to Flovent
• Unable to cooperate with use of MDI
• Pregnant females
• Concurrent or recent (within 3 months) use of systemic corticosteroids.
• Unable to swallow medicines (i.e., fed only by gastrostomy tube).
• Comorbid eosinophilic disorders.
• Previously treated with swallowed glucocorticoid for EE within 3 months of the screening visit. Nasal glucocorticoids taken for EE are permitted.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 3 Years to 30 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00426283
• Other Study ID Numbers: 06-10-07
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Marc Rothenberg, MD, Children's Hospital Medical Center, Cincinnati
• Study Sponsor: Marc Rothenberg, MD
• Collaborators: Not Provided

Investigators

• Principal Investigator: Marc E. Rothenberg, M.D., Ph.D.; Children's Hospital Medical Center, Cincinnati

• PRS Account: Children's Hospital Medical Center, Cincinnati
• Verification Date: September 2020