EosinophiliaPhase 4NCT01524536
Steroid Treatment for Hypereosinophilic Syndrome
A Phase 4 study testing prednisone in people with Eosinophilia and Hypereosinophilic Syndrome, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 7 to 100 years
- Conditions the study is for
- Eosinophilia, Hypereosinophilic Syndrome, Leukocyte Disorder
- What is being tested?
- prednisone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Feb 2012to 10 Dec 2020
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 7 to 100 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Assessment of Glucocorticoid Responsiveness and Mechanisms of Resistance in Hypereosinophilic Syndromes
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.
Read more
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.
Read the 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.
- Being tested
- prednisone
- Keywords
- Hypereosinophilia, Hypereosinophilic Syndrome, Corticosteroids, Therapy, HES
- Medical subject headings
- Eosinophilia, Hypereosinophilic Syndrome, Leukocyte Disorders, Hematologic Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
prednisoneDrug
Glucocorticoids (GC) are considered the first- line therapy for hypereosinophilic syndrome.
| Study group | Role | What they receive |
|---|---|---|
| Steroid Challenge | Other | 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. Receives: Drug: prednisone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 24 hours
Secondary outcomes (8)
Participants With Glucocorticoid Responsiveness - IHES Variant
Participants with idiopathic hypereosinophilic syndromes (IHES) that achieved glucocorticoid responsiveness, suboptimal responsiveness, or without response.
Measured: Baseline (Day 1)
Participants With Glucocorticoid Responsiveness - LHES Variant
Participants with lymphoid hypereosinophilic syndromes (LHES) that achieved glucocorticoid responsiveness, suboptimal responsiveness, or without response.
Measured: Baseline (Day 1)
Participants With Glucocorticoid Responsiveness - MHES Variant
Participants with myeloid hypereosinophilic syndromes (MHES) that achieved glucocorticoid responsiveness, suboptimal responsiveness, or without response.
Measured: Baseline (Day 1)
Participants With Glucocorticoid Responsiveness - Overlap HES Subtypes
Participants with overlap hypereosinophilic syndromes that achieved glucocorticoid responsiveness, suboptimal responsiveness, or without response.
Measured: Baseline (Day 1)
Mean Baseline IgE Level
Mean baseline immunoglobulin E (IgE) level in participants prior to initiation of glucocorticoid
Measured: Baseline (Day 1)
Mean Baseline Absolute Eosinophil Count
Mean baseline absolute eosinophil count in participants prior to initiation of glucocorticoids
Measured: Baseline (Day 1)
Participants With Glucocorticoid Responsiveness - Cardiac Involvement
Cardiac involvement in participants with hypereosinophilic syndromes (HES)
Measured: Baseline (Day 1)
Participants With Glucocorticoid Responsiveness - Pulmonary Involvement
Pulmonary involvement in participants with hypereosinophilic syndromes (HES)
Measured: Baseline (Day 1)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Feb 2012 (estimated)
- Study start16 Feb 2012
- Primary completion10 Dec 2020
- Study completion10 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for EosinophiliaStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Paneez Khoury, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01524536
- Sponsor's protocol ID
- 120026
- Other IDs
- 12-I-0026
- Status last verified
- 22 Feb 2021
- First submitted
- 1 Feb 2012
- Last updated
- 15 Feb 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 19910029Prin 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.
PubMed 2612051Hamilos 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.
PubMed 11447383Stokes 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.
PubMed 31657082
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessment of Glucocorticoid Responsiveness and Mechanisms of Resistance in Hypereosinophilic Syndromes
- ClinicalTrials.gov ID
- NCT01524536
- Acronym / sponsor ID
- 120026
- Keywords
- Hypereosinophilia, Hypereosinophilic Syndrome, Corticosteroids, Therapy, HES
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 16 Feb 2012 (actual)
- Primary completion
- 10 Dec 2020 (actual)
- Study completion
- 10 Dec 2020 (actual)
- First posted
- 2 Feb 2012 (estimated)
- Results
- Posted 15 Feb 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Steroid Challenge | Other | Drug: prednisoneA 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. |
Who may qualify
- Ages
- 7 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| prednisoneGlucocorticoids (GC) are considered the first- line therapy for hypereosinophilic syndrome. | Drug | Steroid Challenge |
Primary outcome
Mean Percent Change in Eosinophil Count After Glucocorticoid Challenge
Time frame: 24 hours
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.
8 secondary outcomes
Participants With Glucocorticoid Responsiveness - IHES Variant
Time frame: Baseline (Day 1)
Participants With Glucocorticoid Responsiveness - LHES Variant
Time frame: Baseline (Day 1)
Participants With Glucocorticoid Responsiveness - MHES Variant
Time frame: Baseline (Day 1)
Participants With Glucocorticoid Responsiveness - Overlap HES Subtypes
Time frame: Baseline (Day 1)
Mean Baseline IgE Level
Time frame: Baseline (Day 1)
Mean Baseline Absolute Eosinophil Count
Time frame: Baseline (Day 1)
Participants With Glucocorticoid Responsiveness - Cardiac Involvement
Time frame: Baseline (Day 1)
Participants With Glucocorticoid Responsiveness - Pulmonary Involvement
Time frame: Baseline (Day 1)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 19910029Ogbogu 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.
- Background: PubMed 2612051Prin 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.
- Background: PubMed 11447383Hamilos 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.
- Derived from this study: PubMed 31657082Stokes 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.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
Related trials for Eosinophilia
RecruitingPhase 2
Dupilumab as Add-On Therapy for Hypereosinophilic Syndrome With Partial Clinical Response to Eosinophil-Depleting Biologic Agents
Hypereosinophilic Syndrome
Recruiting
The Esophageal String Test as a Diagnostic Screening Tool for Eosinophilic Esophagitis Among Africans With Dysphagia in Mali and the United States
Dysphagia, Eosinophilic Esophagitis
Active, not recruitingPhase 3
Efficacy and Safety of Tezepelumab in Patients With Eosinophilic Esophagitis
Eosinophilic Esophagitis
RecruitingObservational study
A Longitudinal Study of Familial Hypereosinophilia (FE): Natural History and Markers of Disease Progression
Eosinophilia, Hypereosinophilic Syndrome
RecruitingObservational study
Natural History and Genetics of Food Allergy and Related Conditions
Food Allergy, Loeys-Dietz Syndrome
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paneez Khoury, M.D. principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing prednisone in people with Eosinophilia and Hypereosinophilic Syndrome, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Feb 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean Percent Change in Eosinophil Count After Glucocorticoid Challenge (time frame: 24 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01524536, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Feb 2022.