Steroid Treatment for Hypereosinophilic Syndrome

• ClinicalTrials.gov Identifier: NCT01524536
• Recruitment Status: Recruiting
• First Posted: February 2, 2012
• Last Update Posted: March 29, 2019
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Information provided by (Responsible Party): National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )

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.

Condition or disease	Intervention/treatment	Phase
Eosinophilia; Hypereosinophilia; Leukocyte Disorder; Hematologic Diseases	Drug: prednisone	Phase 4

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/PDGFRA-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

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 100 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Assessment of Glucocorticoid Responsiveness and Mechanisms of Resistance in Hypereosinophilic Syndromes
• Actual Study Start Date: February 16, 2012
• Estimated Primary Completion Date: December 31, 2023
• Estimated Study Completion Date: December 31, 2023

Arms and Interventions

Arm	Intervention/treatment
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.	Drug: prednisone; Prednisoneis an adrenocortical steroid which is mainly used for antiinflammatory effects in different disorders of many organ systems. It causes profound and varied metabolic effects, modifies the immune response of the body to diverse stimuli, and is also used as replacement therapy for adrenocortical deficient patients.

Outcome Measures

Primary Outcome Measures :

1. 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: completion of Study ]
   This study aims to develop a model to determine whether a single, oral, weight-based dose of GC can predict clinical and biologic response to GC s over the long term in subjects with HES. Subjects with FIP1L1/PDGFRA-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.

Secondary Outcome Measures :

1. To define a group of GC non-responders and/or suboptimal responders for further study of the mechanisms and biologic correlates of GC resistance in HES [ Time Frame: 7-24 weeks post challenge. ]
2. To delineate some of the mechanisms of decreased GC responsiveness in GC-resistant subjects and to assess in-vitro correlates of therapeutic responsiveness in HES [ Time Frame: After a sufficient amount of patients from each patient typed has been enrolled and completed steroid taper ]

Eligibility Criteria

• Ages Eligible for Study: 7 Years to 100 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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:

1. Subject meets diagnostic criteria for HES (AEC >1500/microL, absence of a secondary cause and signs and/or symptoms attributable to the eosinophilia)
2. Willingness to perform the timed steroid challenge
3. Appropriate candidate for GC treatment after challenge
4. 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 at the time of enrollment.
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 evaluation.
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.

Contacts and Locations

Contacts

Contact: Nicole C Holland-Thomas, R.N.; (301) 402-5969; hollandnc@mail.nih.gov

Contact: Paneez Khoury, M.D.; (301) 402-3673; khouryp@niaid.nih.gov

Locations

United States, Maryland

National Institutes of Health Clinical Center, 9000 Rockville Pike; Recruiting

Bethesda, Maryland, United States, 20892

Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 ext TTY8664111010 prpl@cc.nih.gov

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

• Principal Investigator: Paneez Khoury, M.D.; National Institute of Allergy and Infectious Diseases (NIAID)

More Information

Additional Information:

NIH Clinical Center Detailed Web Page 

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.

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.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT01524536 History of Changes
• Other Study ID Numbers: 120026; 12-I-0026
• First Posted: February 2, 2012
• Last Update Posted: March 29, 2019
• Last Verified: March 25, 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) ):

Hypereosinophilia; Hypereosinophilic Syndrome; Corticosteroids; Therapy; HES

Additional relevant MeSH terms:

Hematologic Diseases; Hypereosinophilic Syndrome; Eosinophilia; Leukocyte Disorders; Prednisone; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Antineoplastic Agents, Hormonal; Antineoplastic Agents