Cell Biology of Steroid Resistant Asthma

Asthma Clinical Trial

Official title:

Investigating Biomarkers of Steroid Resistant Asthma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00361920
• Other study ID #: HS-2034
• Status: Completed
• Phase: N/A
• First received: August 7, 2006
• Last updated: March 27, 2017
• Start date: August 2006
• Est. completion date: March 2007

Study information

• Verified date: March 2017
• Source: National Jewish Health
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: March 2007
• Est. primary completion date: March 2007
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• prednisone

Locations

Country	Name	City	State
United States	National Jewish Medical and Research Center	Denver	Colorado

Sponsors (2)

Lead Sponsor	Collaborator
National Jewish Health	Genentech, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Assess whether DEX-induced MKP-1 mRNA levels are decreased in PBMC or whole blood cells of SR, as compared to SS, asthmatics
Primary	Determine whether T cells from SR vs SS asthmatics proliferate in the presence of increasing concentrations of DEX
Primary	Determine whether DEX inhibits IL-6, TNF alpha, and IL-13 secretion in PBMC of SR, as compared to SS, asthmatics
Primary	Examine expression of GCR-beta and GCR alpha mRNA in PBMC of SR, as compared to SS, asthmatics, T
Primary	Analyze PBMC isolated from heparinized blood stored for 18 hours overnight at room temperature for specific aims A through D.