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

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Eosinophilic Esophagitis	Drug: Flovent; Other: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 42 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Double Blinded, Randomized Trial of Swallowed 1760mcg Fluticasone Propionate Versus Placebo in the Treatment of Eosinophilic Esophagitis
• Actual Study Start Date: January 2007
• Actual Primary Completion Date: December 2011
• Actual Study Completion Date: March 2012

Arms and Interventions

Arm	Intervention/treatment
Experimental: Flovent 1760 mcg; Fluticasone propionate 880 mcg twice daily for 3 months	Drug: Flovent; 1760 mcg daily; Other Name: Fluticasone propionate
Placebo Comparator: Placebo; Placebo twice daily for 3 months	Other: Placebo; Placebo

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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".
2. 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.
3. 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.
4. 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
5. 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".

Eligibility Criteria

• Ages Eligible for Study: 3 Years to 30 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Colorado

The Children's Hospital of Denver

Aurora, Colorado, United States, 80045

United States, Ohio

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States, 45229

United States, Pennsylvania

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States, 19104

United States, Utah

University of Utah

Salt Lake City, Utah, United States, 84132

Sponsors and Collaborators

Marc Rothenberg, MD

Investigators

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

More Information

Additional Information:

Cincinnati Center for Eosinophilic Disorders 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Marc Rothenberg, MD, Marc Rothenberg, MD, PhD, Children's Hospital Medical Center, Cincinnati
• ClinicalTrials.gov Identifier: NCT00426283
• Other Study ID Numbers: 06-10-07
• First Posted: January 24, 2007
• Results First Posted: February 3, 2014
• Last Update Posted: October 19, 2020
• Last Verified: September 2020

Keywords provided by Marc Rothenberg, MD, Children's Hospital Medical Center, Cincinnati:

Eosinophilic Esophagitis

Additional relevant MeSH terms:

Eosinophilic Esophagitis; Esophagitis; Esophageal Diseases; Gastrointestinal Diseases; Digestive System 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