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

NCT ID: NCT02534402

Last Updated: 2021-04-30

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-08-31
• Study Completion Date: 2021-12-31

Brief 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.

Detailed 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.

Conditions

Chronic Obstructive Pulmonary Disease

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Prednisone Group

30mg of prednisone PO (orally) everyday for 5 days.

Group Type: EXPERIMENTAL

Prednisone

Intervention Type: DRUG

Administration of prednisone to determine the effect on whole blood gene expression.

Control Group

no treatment

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Prednisone

Administration of prednisone to determine the effect on whole blood gene expression.

Intervention Type: DRUG

Other Intervention Names

Deltasone; Orasone; Prednicen-M; Liquid Pred

Eligibility Criteria

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

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 95 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of British Columbia

OTHER

Sponsor Role: lead

Responsible Party

Don Sin

Dr. Don Sin

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Donald D Sin, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

University of British Columbia, St. Paul's Hospital, James Hogg Research Centre

Locations

St. Paul's Hospital

Vancouver, British Columbia, Canada

Countries

Canada

References

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.

Reference Type: BACKGROUND

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. doi: 10.1016/s0954-6111(03)80022-7.

Reference Type: BACKGROUND

PMID: 12647940 (View on PubMed)

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. doi: 10.1016/j.rmed.2007.10.010. Epub 2007 Dec 20.

Reference Type: BACKGROUND

PMID: 18086519 (View on PubMed)

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. doi: 10.1016/S0140-6736(96)07492-2.

Reference Type: BACKGROUND

PMID: 9167458 (View on PubMed)

Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med. 2006 Nov;3(11):e442. doi: 10.1371/journal.pmed.0030442.

Reference Type: BACKGROUND

PMID: 17132052 (View on PubMed)

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. doi: 10.1001/jama.290.17.2301.

Reference Type: BACKGROUND

PMID: 14600189 (View on PubMed)

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. doi: 10.1517/14728214.11.2.275.

Reference Type: BACKGROUND

PMID: 16634702 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 18216052 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19411661 (View on PubMed)

Takiguchi H, Chen V, Obeidat M, Hollander Z, FitzGerald JM, McManus BM, Ng RT, Sin DD. Effect of short-term oral prednisone therapy on blood gene expression: a randomised controlled clinical trial. Respir Res. 2019 Aug 5;20(1):176. doi: 10.1186/s12931-019-1147-2.

Reference Type: DERIVED

PMID: 31382977 (View on PubMed)

Other Identifiers

H15-01147

Identifier Type: -

Identifier Source: org_study_id