Cell Biology of Steroid Resistant Asthma - Full Text View

Sponsors and Collaborators:	National Jewish Health Genentech
Information provided by:	National Jewish Health
ClinicalTrials.gov Identifier:	NCT00361920

Purpose

The hypothesis is that patients who demonstrate steroid resistant asthma by showing little or no improvement in lung function after a course of oral steroids have different cellular responses to steroids than patients who are steroid sensitive. These altered responses are the reason they demonstrate steroid resistance.

Condition	Intervention
Asthma	Drug: prednisone

MedlinePlus related topics: Asthma

Drug Information available for: Prednisone

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Diagnostic, Non-Randomized, Open Label, Active Control, Single Group Assignment, Pharmacokinetics Study
Official Title:	Investigating Biomarkers of Steroid Resistant Asthma

Further study details as provided by National Jewish Health:

Primary Outcome Measures:

Assess the prevalence of steroid resistance and to determine what fraction of steroid resistant subjects have positive skin tests and IgE levels ≥30 IU/ml
Assess whether DEX-induced MKP-1 mRNA levels are decreased in PBMC or whole blood cells of SR, as compared to SS, asthmatics
Determine whether T cells from SR vs SS asthmatics proliferate in the presence of increasing concentrations of DEX
Determine whether DEX inhibits IL-6, TNF alpha, and IL-13 secretion in PBMC of SR, as compared to SS, asthmatics
Examine expression of GCR-beta and GCR alpha mRNA in PBMC of SR, as compared to SS, asthmatics, T
Analyze PBMC isolated from heparinized blood stored for 18 hours overnight at room temperature for specific aims A through D.

Estimated Enrollment:	40
Study Start Date:	August 2006
Estimated Study Completion Date:	March 2007

Detailed Description:

Current NHLBI guidelines for persistent asthma management recommends the use of steroids for treatment of airway inflammation (1,2). However, some asthmatics do not respond to steroids (3-6). Unfortunately these patients are subjected to the unwanted side effects (osteoporosis, cataracts, etc) of high dose steroid therapy because non-immune tissues remain sensitive to steroids. Recent studies suggest that the costs of asthma are largely attributable to uncontrolled disease (7). Thus, it is important to understand the mechanism(s) of steroid resistance and introduce new forms of therapy for the treatment of these difficult to control asthmatics. As a prelude to pharmaceutical studies in steroid resistant asthma, it is imperative to develop biomarkers that can robustly identify individuals likely to be poor steroid responders so that alternative non-steroid anti-inflammatory therapies, such as Xolair®, can be introduced early in the course of asthma therapy.

Eligibility

Ages Eligible for Study:	12 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Will meet American Thoracic Society criteria for asthma
Pulmonary function tests consistent with asthma. This includes a baseline FEV1 < 80% predicted as well as a 12% improvement in FEV1 following up to 4 puffs of albuterol.
Subjects must be 12 to 65 years old.

Exclusion Criteria:

Viral infection within four weeks of the starting date.
Abnormal hepatic function.
History of COPD
Pregnancy.
History of smoking.
Anemia (hemoglobin less than 12 gm %)
Concurrent therapy with anticonvulsants, erythromycin, rifampin and any systemic asthma medication including Singular®, Xolair® or oral prednisone.
Greater than 500 mcg per day of inhaled corticosteroids
Suspected non-compliance with medical care.
Abnormal prednisone pharmacokinetics (applies to phase 2 of trial)
Patients with severe medical conditions that in the view of the investigator prohibits participation in the study (specify as required)
Use of any investigational agent in the last 30 days

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00361920

Contacts

Contact: Craig Jones, BS	303-398-1672	jonesc@njc.org
Contact: Kate Morgan, BS	303-398-1026	morgank@njc.org

Locations

United States, Colorado
National Jewish Medical and Research Center	Recruiting
Denver, Colorado, United States, 80206

Sponsors and Collaborators

National Jewish Health

Genentech

Investigators

Principal Investigator:

Donald Leung, MD,PhD

National Jewish Health

More Information

Study ID Numbers:	HS-2034
Study First Received:	August 7, 2006
Last Updated:	September 20, 2006
ClinicalTrials.gov Identifier:	NCT00361920
Health Authority:	United States: Institutional Review Board

Keywords provided by National Jewish Health:

steroid resistant asthma

Study placed in the following topic categories:

Prednisone
Hypersensitivity
Lung Diseases, Obstructive
Respiratory Tract Diseases

Lung Diseases
Hypersensitivity, Immediate
Asthma
Respiratory Hypersensitivity

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Antineoplastic Agents, Hormonal
Immune System Diseases
Bronchial Diseases
Antineoplastic Agents
Therapeutic Uses

Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Hormones
Glucocorticoids
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 15, 2009