Evaluating Genes in Sputum to Measure Drug Response in COPD

Condition(s) targeted: Chronic Obstructive Pulmonary Disease (COPD); Emphysema; Chronic Bronchitis

Intervention: Salmeterol or Salmeterol/Fluticasone (Drug)

Phase: N/A

Status: Terminated

Sponsored by: National Jewish Medical and Research Center

Official(s) and/or principal investigator(s):
E Rand Sutherland, MD, MPH, Principal Investigator, Affiliation: National Jewish Medical and Research Center Faculty

The purpose of this research study is to determine whether analysis of genes in sputum is a useful noninvasive technique for measuring response to drugs in patients with COPD.

We propose to use polymerase chain reaction to evaluate gene expression in induced sputum from adult current smokers with moderate COPD, adult former smokers with moderate COPD. This study is designed to determine whether changes in expression of previously-identified inflammatory markers in induced sputum can be detected in response to drug therapy in COPD and to evaluate potential differences in the expression of these markers in adult smokers with and without COPD. Pre- and post-treatment serum will be obtained to facilitate proteomic analysis of therapeutic response as well. Changes in sputum gene expression in response to treatment will be the primary outcome variable in this study. Secondary outcomes will include changes in lung function, as well as changes in induced sputum inflammation. These endpoints will be evaluated before and directly after 6 weeks of randomly-assigned treatment with either salmeterol xinafoate or fluticasone propionate/50mcg salmeterol xinafoate combination DPI bid. Endpoints will be re-evaluated following a 4 week wash-out period.

Official title: Expression of Inflammatory Mediators in Induced Sputum: A Potential Biomarker of Drug Response in COPD

Study design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study

Primary outcome: Induced Sputum Gene Expression

Secondary outcome: Lung Function

Minimum age: 40 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Twenty adult subjects ≥ 40 years of age and ≥ 10 pack/year cigarette history will be

evaluated.

- Subjects will be recruited such that one-half are current smokers and one-half are

former smokers.

- All subjects will have COPD (FEV1/FVC < 70% and FEV1 => 40% predicted).

- Airway hyperresponsiveness and diffusion capacity for carbon monoxide will also be

performed to more precisely characterize the physiologic phenotype in these subjects.

Exclusion Criteria:

- Subjects will be excluded if they have used inhaled or systemic corticosteroid or

antibiotic use within 6 weeks or if they are currently treated with theophylline.

- A 6 weeks run off after an upper respiratory infection will be required for qualifying

subjects.

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

clinical lab website within National Jewish Medical and Research Center

Starting date: April 2003
Last updated: June 21, 2006