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Steroid Treatment for Hypereosinophilic Syndrome

Primary Purpose

Eosinophilia, Hypereosinophilic Syndrome, Leukocyte Disorder

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
prednisone
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Eosinophilia focused on measuring Hypereosinophilia, Hypereosinophilic Syndrome, Corticosteroids, Therapy, HES

Eligibility Criteria

7 Years - 100 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers
  • SUBJECT INCLUSION CRITERIA:

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.

Sites / Locations

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Steroid Challenge

Arm Description

A single oral dose of prednisone (1 mg/kg rounded to the nearest 5mg) was administered to all participants. The following day, participant began glucocorticoid therapy of prednisone 30 mg oral daily for one week followed by a standardized taper until a minimally effective dose was achieved or participant tapered to prednisone 5 mg oral daily.

Outcomes

Primary Outcome Measures

Mean Percent Change in Eosinophil Count After Glucocorticoid Challenge
Response to glucocorticoid challenge as assessed by the percentage of the eosinophil count 24 hours post-glucocorticoid challenge relative to the Baseline AEC for each participant. Measure Description (%): Percent of baseline AEC is defined as the Absolute Eosinophil Count at 24 hours divided by the Absolute Eosinophil Count at Baseline *100.

Secondary Outcome Measures

Participants With Glucocorticoid Responsiveness - IHES Variant
Participants with idiopathic hypereosinophilic syndromes (IHES) that achieved glucocorticoid responsiveness, suboptimal responsiveness, or without response.
Participants With Glucocorticoid Responsiveness - LHES Variant
Participants with lymphoid hypereosinophilic syndromes (LHES) that achieved glucocorticoid responsiveness, suboptimal responsiveness, or without response.
Participants With Glucocorticoid Responsiveness - MHES Variant
Participants with myeloid hypereosinophilic syndromes (MHES) that achieved glucocorticoid responsiveness, suboptimal responsiveness, or without response.
Participants With Glucocorticoid Responsiveness - Overlap HES Subtypes
Participants with overlap hypereosinophilic syndromes that achieved glucocorticoid responsiveness, suboptimal responsiveness, or without response.
Mean Baseline IgE Level
Mean baseline immunoglobulin E (IgE) level in participants prior to initiation of glucocorticoid
Mean Baseline Absolute Eosinophil Count
Mean baseline absolute eosinophil count in participants prior to initiation of glucocorticoids
Participants With Glucocorticoid Responsiveness - Cardiac Involvement
Cardiac involvement in participants with hypereosinophilic syndromes (HES)
Participants With Glucocorticoid Responsiveness - Pulmonary Involvement
Pulmonary involvement in participants with hypereosinophilic syndromes (HES)

Full Information

First Posted
February 1, 2012
Last Updated
January 26, 2022
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
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1. Study Identification

Unique Protocol Identification Number
NCT01524536
Brief Title
Steroid Treatment for Hypereosinophilic Syndrome
Official Title
Assessment of Glucocorticoid Responsiveness and Mechanisms of Resistance in Hypereosinophilic Syndromes
Study Type
Interventional

2. Study Status

Record Verification Date
February 22, 2021
Overall Recruitment Status
Completed
Study Start Date
February 16, 2012 (Actual)
Primary Completion Date
December 10, 2020 (Actual)
Study Completion Date
December 10, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Eosinophilia, Hypereosinophilic Syndrome, Leukocyte Disorder, Hematologic Diseases
Keywords
Hypereosinophilia, Hypereosinophilic Syndrome, Corticosteroids, Therapy, HES

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
26 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Steroid Challenge
Arm Type
Other
Arm Description
A single oral dose of prednisone (1 mg/kg rounded to the nearest 5mg) was administered to all participants. The following day, participant began glucocorticoid therapy of prednisone 30 mg oral daily for one week followed by a standardized taper until a minimally effective dose was achieved or participant tapered to prednisone 5 mg oral daily.
Intervention Type
Drug
Intervention Name(s)
prednisone
Intervention Description
Glucocorticoids (GC) are considered the first- line therapy for hypereosinophilic syndrome.
Primary Outcome Measure Information:
Title
Mean Percent Change in Eosinophil Count After Glucocorticoid Challenge
Description
Response to glucocorticoid challenge as assessed by the percentage of the eosinophil count 24 hours post-glucocorticoid challenge relative to the Baseline AEC for each participant. Measure Description (%): Percent of baseline AEC is defined as the Absolute Eosinophil Count at 24 hours divided by the Absolute Eosinophil Count at Baseline *100.
Time Frame
24 hours
Secondary Outcome Measure Information:
Title
Participants With Glucocorticoid Responsiveness - IHES Variant
Description
Participants with idiopathic hypereosinophilic syndromes (IHES) that achieved glucocorticoid responsiveness, suboptimal responsiveness, or without response.
Time Frame
Baseline (Day 1)
Title
Participants With Glucocorticoid Responsiveness - LHES Variant
Description
Participants with lymphoid hypereosinophilic syndromes (LHES) that achieved glucocorticoid responsiveness, suboptimal responsiveness, or without response.
Time Frame
Baseline (Day 1)
Title
Participants With Glucocorticoid Responsiveness - MHES Variant
Description
Participants with myeloid hypereosinophilic syndromes (MHES) that achieved glucocorticoid responsiveness, suboptimal responsiveness, or without response.
Time Frame
Baseline (Day 1)
Title
Participants With Glucocorticoid Responsiveness - Overlap HES Subtypes
Description
Participants with overlap hypereosinophilic syndromes that achieved glucocorticoid responsiveness, suboptimal responsiveness, or without response.
Time Frame
Baseline (Day 1)
Title
Mean Baseline IgE Level
Description
Mean baseline immunoglobulin E (IgE) level in participants prior to initiation of glucocorticoid
Time Frame
Baseline (Day 1)
Title
Mean Baseline Absolute Eosinophil Count
Description
Mean baseline absolute eosinophil count in participants prior to initiation of glucocorticoids
Time Frame
Baseline (Day 1)
Title
Participants With Glucocorticoid Responsiveness - Cardiac Involvement
Description
Cardiac involvement in participants with hypereosinophilic syndromes (HES)
Time Frame
Baseline (Day 1)
Title
Participants With Glucocorticoid Responsiveness - Pulmonary Involvement
Description
Pulmonary involvement in participants with hypereosinophilic syndromes (HES)
Time Frame
Baseline (Day 1)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
7 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
SUBJECT INCLUSION CRITERIA: Subjects on Protocol #94-I-0079 will be eligible for participation in the study only if all of the following criteria apply: Subjects must be 7 years of age or older to enroll Subject meets diagnostic criteria for HES (AEC >1500/microL, absence of a secondary cause and signs and/or symptoms attributable to the eosinophilia) AEC greater than 1500 microL obtained within 14 days prior to enrollment Willingness to perform the timed steroid challenge Appropriate candidate for GC treatment after challenge 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: Receiving >10 mg prednisone or equivalent at the time of enrollment. 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). AEC less than or equal to 1500/microl on the day of the steroid challenge 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. Pregnant at the time of screening. Have a known mutation in the FIP1L1-PDGFR gene. Any condition that, in the opinion of the investigator, places the subject at undue risk by participating in the protocol. Weight less than 48 kg (106 lbs) in subjects less than 18 years of age.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paneez Khoury, M.D.
Organizational Affiliation
National Institute of Allergy and Infectious Diseases (NIAID)
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Institutes of Health Clinical Center, 9000 Rockville Pike
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
19910029
Citation
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.
Results Reference
background
PubMed Identifier
2612051
Citation
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.
Results Reference
background
PubMed Identifier
11447383
Citation
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. doi: 10.1067/mai.2001.116428.
Results Reference
background
PubMed Identifier
31657082
Citation
Stokes K, Yoon P, Makiya M, Gebreegziabher M, Holland-Thomas N, Ware J, Wetzler L, Khoury P, Klion AD. Mechanisms of glucocorticoid resistance in hypereosinophilic syndromes. Clin Exp Allergy. 2019 Dec;49(12):1598-1604. doi: 10.1111/cea.13509. Epub 2019 Oct 27.
Results Reference
derived
Links:
URL
https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2012-I-0026.html
Description
NIH Clinical Center Detailed Web Page

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Steroid Treatment for Hypereosinophilic Syndrome

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