Prednisone Administration in Quiescent COPD Patients to Determine the Effect on Gene Expression

Chronic Obstructive Pulmonary Disease Clinical Trial

Official title:

Clinical Implementation and Outcomes Evaluation of Blood-Based Biomarkers for COPD Management: COPD Prednisone Sub-Study

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02534402
• Other study ID #: H15-01147
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: August 2015
• Est. completion date: December 2021

Study information

• Verified date: April 2021
• Source: University of British Columbia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

In this study, prednisone dose, day/time administration will be controlled in a stable COPD patient population to determine its effect on peripheral whole blood gene expression. This data has never been collected in a COPD population using the investigators' chosen platform for gene expression (Affymetrix Human Gene 1.1 ST). Conducting this experiment is essential for achieving the broader aims of an already existing and related study titled "Clinical Implementation and Outcomes Evaluation of Blood-Based Biomarkers for COPD Management" study. As part of this existing study, blood is being collected from hospitalized and non-hospitalized COPD patients in order to develop a blood-based biomarker test for the diagnosis and prediction of acute exacerbation of COPD (AECOPD). The majority of these patients were administered prednisone as part of standard care for the treatment of AECOPD. As such, the effect of prednisone on gene expression needs to be ruled out.

Description:

The course of COPD is frequently complicated by periods of exacerbation (worsening symptoms) related to infections, pollution, other diseases or poor management of disease. These periods result in urgent visits to physician offices or emergency rooms accounting for the leading cause of hospitalizations. In terms of patient care, physicians lack objective measurements to accurately risk-stratify patients and monitor the effectiveness of interventions provided for their patients. Regrettably, there are no blood tests that can predict who will and will not get AECOPD to require hospitalization. Additionally, current therapies for COPD are only modestly effective in reducing exacerbations. A major challenge in COPD drug development and patient care is the lack of markers, surrogate or otherwise, that can be used to predict outcomes such as hospitalization or mortality.

These critical barriers to drug development and improved patient care could be addressed by the development and clinical implementation of diagnostic and predictive AECOPD biomarkers. This is the aim of an already existing and related study titled "Clinical Implementation and Outcomes Evaluation of Blood-Based Biomarkers for COPD Management study". This study has been enrolling COPD patients since July 2012. The majority of the the study patients were on prednisone at the time of blood collection and at enrollment.

The analyses of publicly available datasets make it abundantly clear that prednisone has important and wide-ranging effects on peripheral whole blood gene expression. These data are insufficient, however, because they cannot inform disease specific effects on gene expression. In addition, because these studies were carried out using a different gene expression platform, they cannot be used to estimate the probeset-specific prednisone effects.

Therefore, the investigators need to ensure that the gene expression associated with AECOPD is not in fact a result of the drug effect. Conducting this study will help us answer this question.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 40
• Est. completion date: December 2021
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years to 95 Years

Eligibility

Inclusion Criteria:

• Participants diagnosed with COPD

Exclusion Criteria:

• Participants currently taking prednisone

• Participants who received prednisone within the last 2 weeks

• Participants who were hospitalized in the last 2 weeks for COPD or a related respiratory condition

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Prednisone
Administration of prednisone to determine the effect on whole blood gene expression.

Locations

Country	Name	City	State
Canada	St. Paul's Hospital	Vancouver	British Columbia

Sponsors (1)

Lead Sponsor	Collaborator
University of British Columbia

Country where clinical trial is conducted

Canada, 

References & Publications (9)

Chapman KR, Bourbeau J, Rance L. The burden of COPD in Canada: results from the Confronting COPD survey. Respir Med. 2003 Mar;97 Suppl C:S23-31. — View Citation

Global Initiative for Chronic Obstructive Lung Disease, Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease (Updated 2009). http://www.goldcopd.com/Guidelineitem.asp?l1=2&l2=1&intId=2003.

Kuzyk MA, Smith D, Yang J, Cross TJ, Jackson AM, Hardie DB, Anderson NL, Borchers CH. Multiple reaction monitoring-based, multiplexed, absolute quantitation of 45 proteins in human plasma. Mol Cell Proteomics. 2009 Aug;8(8):1860-77. doi: 10.1074/mcp.M800540-MCP200. Epub 2009 May 1. — View Citation

Malhotra S, Man SF, Sin DD. Emerging drugs for the treatment of chronic obstructive pulmonary disease. Expert Opin Emerg Drugs. 2006 May;11(2):275-91. Review. — View Citation

Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med. 2006 Nov;3(11):e442. — View Citation

Mittmann N, Kuramoto L, Seung SJ, Haddon JM, Bradley-Kennedy C, Fitzgerald JM. The cost of moderate and severe COPD exacerbations to the Canadian healthcare system. Respir Med. 2008 Mar;102(3):413-21. Epub 2007 Dec 20. — View Citation

Murray CJ, Lopez AD. Alternative projections of mortality and disability by cause 1990-2020: Global Burden of Disease Study. Lancet. 1997 May 24;349(9064):1498-504. — View Citation

Sin DD, McAlister FA, Man SF, Anthonisen NR. Contemporary management of chronic obstructive pulmonary disease: scientific review. JAMA. 2003 Nov 5;290(17):2301-12. Review. — View Citation

Vestbo J, Anderson W, Coxson HO, Crim C, Dawber F, Edwards L, Hagan G, Knobil K, Lomas DA, MacNee W, Silverman EK, Tal-Singer R; ECLIPSE investigators. Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE). Eur Respir J. 2008 Apr;31(4):869-73. doi: 10.1183/09031936.00111707. Epub 2008 Jan 23. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Effect of prednisone on peripheral whole blood gene expression	Effect of prednisone on peripheral whole blood gene expression of stable COPD patients, assayed using Affymetrix Human Gene 1.1 ST microarrays. This outcome measure will be assessed at each blood draw.	Period of 5 days