Cell Biology of Steroid Resistant Asthma

This study has been completed.
Sponsor:
Collaborator:
Genentech
Information provided by:
National Jewish Health
ClinicalTrials.gov Identifier:
NCT00361920
First received: August 7, 2006
Last updated: September 24, 2014
Last verified: September 2014
  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

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Investigating Biomarkers of Steroid Resistant Asthma

Resource links provided by NLM:


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
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:

  1. Will meet American Thoracic Society criteria for asthma
  2. 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.
  3. Subjects must be 12 to 65 years old.

Exclusion Criteria:

  1. Viral infection within four weeks of the starting date.
  2. Abnormal hepatic function.
  3. History of COPD
  4. Pregnancy.
  5. History of smoking.
  6. Anemia (hemoglobin less than 12 gm %)
  7. Concurrent therapy with anticonvulsants, erythromycin, rifampin and any systemic asthma medication including Singular®, Xolair® or oral prednisone.
  8. Greater than 500 mcg per day of inhaled corticosteroids
  9. Suspected non-compliance with medical care.
  10. Abnormal prednisone pharmacokinetics (applies to phase 2 of trial)
  11. Patients with severe medical conditions that in the view of the investigator prohibits participation in the study (specify as required)
  12. Use of any investigational agent in the last 30 days
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, Colorado
National Jewish Medical and Research Center
Denver, Colorado, United States, 80206
Sponsors and Collaborators
National Jewish Health
Genentech
Investigators
Principal Investigator: Donald Leung, MD,PhD National Jewish Health
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00361920     History of Changes
Other Study ID Numbers: HS-2034
Study First Received: August 7, 2006
Last Updated: September 24, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by National Jewish Health:
steroid resistant asthma

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases

ClinicalTrials.gov processed this record on October 01, 2014