The Effect of Statins in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Study Description

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief Summary:

Chronic obstructive pulmonary disease (COPD) is a condition of the lungs which results in breathing difficulties due to the lungs becoming inflamed and the airways narrowed. Current treatments have focused on opening up the narrowed airways but, in addition, we know there is increased inflammation in the blood and these patients are at increased risk of heart disease. Statins, simvastatin being one of them, are drugs used to lower cholesterol in the blood but may also reduce inflammation and lower the risk of heart disease. This study will explore whether simvastatin reduces one of the risk factors in patients with COPD in a short term proof of principle study. The key purpose is to determine whether simvastatin improves the pressure and stiffness of the main blood vessels namely the arterial stiffness measure of aortic pulse wave velocity (PWV). In parallel, we will describe changes in airways and / or blood inflammation and change in breathing ability

Condition or disease	Intervention/treatment	Phase
Chronic Obstructive Pulmonary Disease	Drug: Simvastatin; Drug: Lactose tablet	Phase 4

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	70 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	The Cardiovascular and Inflammatory Effects of Statin Therapy in Patients With COPD
Study Start Date :	June 2010
Actual Primary Completion Date :	April 2013
Actual Study Completion Date :	August 2013

Arms and Interventions

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
Placebo Comparator: Lactose tablet	Drug: Lactose tablet; One tablet taken each evening for 6 weeks
Active Comparator: Simvastatin 20mg	Drug: Simvastatin; Simvastatin 20mg once daily (in the evening) for 6 weeks

Outcome Measures

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Primary Outcome Measures :

1. Change in arterial stiffness as measured by aortic pulse wave velocity (PWV) over study period [ Time Frame: Week 0 (start) and week 6 (end) ]
   Aortic Pulse wave velocity (Sphygmocor, Atcor)

Secondary Outcome Measures :

1. Change in Circulating Inflammatory Mediators over study period [ Time Frame: Week 0 (Start) and week 6 (End) ]
2. Change in distance (metres)walked on 6 minute walking test [ Time Frame: week 0 (start) and week 6 (end) ]
   together with pre- and post-walk oxygen saturations
3. Change in blood total cholesterol, triglycerides, HDL and LDL over study period [ Time Frame: week 0 (Start) and week 6 (End) ]
4. Change in airway inflammatory markers (differential cell count, exhaled nitric oxide and airway cytokines) over study period [ Time Frame: week 0 and week 6 ]
5. Change in lung function: Spirometry - forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) [ Time Frame: week 0 (Start) and week 6 (End) ]
6. Change on blood pressure over study period [ Time Frame: Week 0 (start) and Week 6 (end) ]
7. Change in Liver function tests [ Time Frame: Week 0 (start) and Week 6 (End) ]
8. Change in creatine phosphokinase (CPK) over study period [ Time Frame: Week 0 (start) and Week 6(End) ]
9. Change in Handgrip strength over study period [ Time Frame: Week 0 (start) and Week 6 (end) ]
10. Change in blood desmosine over study period [ Time Frame: Week 0 (Start) and Week 6 (end) ]
11. Change in circulating matrix metalloproteinase over study period [ Time Frame: Week 0 (start) and Week 6 (end) ]
12. Baseline arterial stiffness (aortic pulse wave velocity) [ Time Frame: Week 0 ]
13. Baseline airway (differential cell count, exhaled nitric oxide and cytokines)and circulating inflammatory status (cytokines) [ Time Frame: Week 0 ]
14. Baseline matrix metalloproteinase in airway and blood [ Time Frame: Week 0 ]

Eligibility Criteria

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Ages Eligible for Study:	45 Years to 80 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Male or female patients aged 45-80 years;
• Confirmed COPD: FEV1 30-80% predicted, FEV1/FVC<0.7, salbutamol reversibility <12%, supportive smoking history
• If female of childbearing potential, have a negative serum pregnancy test at screening and use a medically acceptable form of contraception starting at screening and continuing throughout the study (defined as an oral contraceptive, or barrier method combined with a spermicide)
• Able to attend for regular clinic appointments
• In opinion of investigator, the patient will be able to comply with the requirements of the protocol
• Provide written informed consent.

Exclusion Criteria:

• Known hypersensitivity to or side effects relating to previous statin treatment, or current therapy which includes a statin, ezetimibe or fibrate
• Clinically significant liver function abnormality; alcohol excess
• Hypercholesterolaemia > or equal to 6.5mmol/L
• Females who are pregnant, breast feeding, or at risk of pregnancy and not using a medically acceptable form of contraception.
• Any condition judged by investigator that would cause the study to be detrimental to patient.
• Conditions: rheumatoid disease/other collagen vascular disease requiring therapy; diabetes mellitus; untreated hypothyroidism; inflammatory bowel disease; other respiratory disease; known alpha 1 antitrypsin deficiency; malignancy; documented history of ischaemic heart disease (IHD); cor pulmonale or known congestive heart failure; patients planning to undergo elective surgery during the study period.
• Exacerbation in the last 4 weeks.
• Significant hypoxia (PaO2 <7.3kPa)
• Known lactose intolerance.
• Therapies: oral prednisolone for more than 1 week in the last 6 months; disease modifying drugs (Gold/ sulphasalazine etc); weight losing drugs; concomitant use of warfarin, cyclosporine; concomitant administration of potent CYP3A4 inhibitors (e.g. itraconazole, ketoconazole, HIV protease inhibitors, erythromycin, clarithromycin, telithromycin and nefazodone). Use of any investigational drug within four weeks of the baseline visit.

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

United Kingdom
Nottingham Respiratory Biomedical Research Unit
Nottingham, United Kingdom, NG5 1PB

Sponsors and Collaborators

University of Nottingham

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

John ME, Cockcroft JR, McKeever TM, Coward WR, Shale DJ, Johnson SR, Thornton JG, Harrison TW, Knox AJ, Bolton CE. Cardiovascular and inflammatory effects of simvastatin therapy in patients with COPD: a randomized controlled trial. Int J Chron Obstruct Pulmon Dis. 2015 Jan 29;10:211-21. doi: 10.2147/COPD.S76061. eCollection 2015.

Responsible Party:	University of Nottingham
ClinicalTrials.gov Identifier:	NCT01151306 History of Changes
Other Study ID Numbers:	09105
First Posted:	June 28, 2010
Last Update Posted:	March 24, 2014
Last Verified:	March 2014

Additional relevant MeSH terms:

Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Diseases; Simvastatin; Anticholesteremic Agents	Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Enzyme Inhibitors