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

The Cardiovascular and Inflammatory Effects of Statin Therapy in Patients With COPD

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

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: Lactose tablet; Drug: Simvastatin

• Study Type: Interventional
• Enrollment (Anticipated): 70
• Phase: Phase 4

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in arterial stiffness as measured by aortic pulse wave velocity (PWV) over study period	Aortic Pulse wave velocity (Sphygmocor, Atcor)	Week 0 (start) and week 6 (end)

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: University of Nottingham

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Actual): April 1, 2013
• Study Completion (Actual): August 1, 2013

Study Registration Dates

• First Submitted: June 21, 2010
• First Submitted That Met QC Criteria: June 25, 2010
• First Posted (Estimate): June 28, 2010

Study Record Updates

• Last Update Posted (Estimate): March 24, 2014
• Last Update Submitted That Met QC Criteria: March 21, 2014
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Simvastatin
• Other Study ID Numbers: 09105