Steroid Treatment for Hypereosinophilic Syndrome


Background: – Hypereosinophilic syndrome (HES) is a disorder in which the body has too many eosinophils (a type of white blood cell). Too many eosinophils in HES can cause damage to the heart, nerves, or skin. Certain drugs can help lower eosinophil counts to prevent tissue damage. Corticosteroids, such as prednisone, are used for initial therapy in this disorder. Although most people respond to prednisone, some people develop side effects from it, or do not respond very well to treatment. Better ways of determining the dose to give could help to decide on the best therapy for HES. Objectives: – To determine whether a single-dose of prednisone can be used to predict which people with hypereosinophilia respond to treatment. – To study lack of response to steroid treatment in people with HES. Eligibility: Inclusion criteria: – Individuals with hypereosinophilic syndrome with high eosinophil counts. – Individuals who are willing to have blood drawn before and after getting steroids. Exclusion criteria: – Individuals who are on more than 10mg of prednisone (or similar drug) – Individuals with hypereosinophilic syndrome who are on other medications that could interfere with the study – Women who are pregnant or breast-feeding – Individuals who have a known gene mutation associated with chronic eosinophilic leukemia – Children less than 18 years old who weigh less than 48kg or 106lb Design: – Participants will have a screening visit with a physical exam and medical history. Blood and urine samples will be collected. – Participants will have a single dose of the steroid prednisone by mouth in the morning. Blood samples will be collected 2, 4, 24 hours after this dose. – On the day after the steroid dose, participants will provide another blood sample in the morning. – Participants will start to take prednisone daily when they return home. Blood samples will be collected weekly at the participant s doctor s office. The dose of prednisone will be lowered depending on the weekly eosinophil count. We will try to get each person on the lowest dose of prednisone possible that will control the disorder. Participants who do not respond or have severe side effects will be taken off prednisone. Other treatments will be considered for people who do not respond to steroids. The goal is to evaluate the response to prednisone. Our research will try to figure out why some people do not respond to steroids. Most people will complete the study within 6 to 16 weeks, depending on their response to prednisone.

Full Title of Study: “Assessment of Glucocorticoid Responsiveness and Mechanisms of Resistance in Hypereosinophilic Syndromes”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: December 10, 2020

Detailed Description

This study aims to develop a model to determine whether a single, oral, weight-based dose of glucocorticoid (GC) can predict clinical and biologic response to GC s over the long term in subjects with hypereosinophilic syndrome (HES). Subjects with FIP1L1/PDGFRalpha-negative HES, who are symptomatic with eosinophil count >1500/microL and receiving less than or equal to10 mg prednisone daily, will be enrolled. A single oral dose of prednisone (1 mg/kg rounded to the nearest 5mg) will be administered. Eosinophil count and various laboratory parameters will be assessed at 2 hours, 4 hours and 24 hours following prednisone administration (investigators will be blinded to the results of the eosinophil counts). The subjects will then begin GC therapy at 30 mg prednisone daily followed by a standardized taper. The lowest dose of GC at which symptoms and eosinophilia are controlled will be compared to the change in eosinophil count at 2, 4 and 24 hours post-challenge. Mechanisms and in vitro correlates of GC resistance will also be explored.


  • Drug: prednisone
    • Glucocorticoids are considered the first- line therapy for hypereosinophilic syndrome. Although decreased expression of the GC receptor on the surface of eosinophils was implicated in 3 out of 5 patients with GC-resistant HES, the mechanisms of decreased or absent GC response is largely unexplored.

Arms, Groups and Cohorts

  • Other: 1
    • All subjects will receive a single oral dose of prednison (1 mg/kg rounded to the neares 5 mg). The subjects will then begin GC therapy at 30 mg prednisone daily followed by a standardized taper.

Clinical Trial Outcome Measures

Primary Measures

  • To develop a model to determine whether a single dose steroid challenge can be used to predict GC responsiveness in subjects with HES.
    • Time Frame: One year after final subject has completed study
    • To develop a model to determine whether a single dose steroid challenge can be used to predict GC responsiveness in subjects with HES.

Participating in This Clinical Trial

  • Subjects on Protocol #94-I-0079 will be eligible for participation in the study only if all of the following criteria apply: 1. Subjects must be 7 years of age or older to enroll 2. Subject meets diagnostic criteria for HES (AEC >1500/microL, absence of a secondary cause and signs and/or symptoms attributable to the eosinophilia) 3. AEC greater than 1500 microL obtained within 14 days prior to enrollment 4. Willingness to perform the timed steroid challenge 5. Appropriate candidate for GC treatment after challenge 6. Willingness to have samples stored for future research SUBJECT EXCLUSION CRITERIA:

    A subject will not be eligible to participate in the study if any of the following apply: 1. Receiving >10 mg prednisone or equivalent at the time of enrollment. 2. Receiving less than or equal to 10 mg of prednisone or equivalent but have not been on a fixed dose for at least 3 weeks (subjects on a current corticosteroid taper will be excluded). 3. AEC less than or equal to 1500/microl on the day of the steroid challenge 4. Use of immunomodulatory medications, (other than less than or equal to 10 mg/day prednisone) including but not limited to biologics, within the past 6 months. 5. Pregnant at the time of screening. 6. Have a known mutation in the FIP1L1-PDGFR gene. 7. Any condition that, in the opinion of the investigator, places the subject at undue risk by participating in the protocol. 8. Weight less than 48 kg (106 lbs) in subjects less than 18 years of age.

    Gender Eligibility: All

    Minimum Age: 7 Years

    Maximum Age: 100 Years

    Are Healthy Volunteers Accepted: No

    Investigator Details

    • Lead Sponsor
      • National Institute of Allergy and Infectious Diseases (NIAID)
    • Provider of Information About this Clinical Study
      • Sponsor
    • Overall Official(s)
      • Paneez Khoury, M.D., Principal Investigator, National Institute of Allergy and Infectious Diseases (NIAID)


    Ogbogu PU, Bochner BS, Butterfield JH, Gleich GJ, Huss-Marp J, Kahn JE, Leiferman KM, Nutman TB, Pfab F, Ring J, Rothenberg ME, Roufosse F, Sajous MH, Sheikh J, Simon D, Simon HU, Stein ML, Wardlaw A, Weller PF, Klion AD. Hypereosinophilic syndrome: a multicenter, retrospective analysis of clinical characteristics and response to therapy. J Allergy Clin Immunol. 2009 Dec;124(6):1319-25.e3. doi: 10.1016/j.jaci.2009.09.022.

    Prin L, Lefebvre P, Gruart V, Capron M, Storme L, Formstecher P, Loiseau S, Capron A. Heterogeneity of human eosinophil glucocorticoid receptor expression in hypereosinophilic patients: absence of detectable receptor correlates with resistance to corticotherapy. Clin Exp Immunol. 1989 Dec;78(3):383-9.

    Hamilos DL, Leung DY, Muro S, Kahn AM, Hamilos SS, Thawley SE, Hamid QA. GRbeta expression in nasal polyp inflammatory cells and its relationship to the anti-inflammatory effects of intranasal fluticasone. J Allergy Clin Immunol. 2001 Jul;108(1):59-68.

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