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

Chronic Obstructive Pulmonary Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01151306
• Other study ID #: 09105
• Status: Completed
• Phase: Phase 4
• First received: June 21, 2010
• Last updated: March 21, 2014
• Start date: June 2010
• Est. completion date: August 2013

Study information

• Verified date: March 2014
• Source: University of Nottingham
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: August 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 45 Years to 80 Years

Eligibility

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 Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Drug:
• Simvastatin
Simvastatin 20mg once daily (in the evening) for 6 weeks
• Lactose tablet
One tablet taken each evening for 6 weeks

Locations

Country	Name	City	State
United Kingdom	Nottingham Respiratory Biomedical Research Unit	Nottingham

Sponsors (1)

Lead Sponsor	Collaborator
University of Nottingham

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Secondary	Change in Circulating Inflammatory Mediators over study period		Week 0 (Start) and week 6 (End)	No
Secondary	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)	No
Secondary	Change in blood total cholesterol, triglycerides, HDL and LDL over study period		week 0 (Start) and week 6 (End)	No
Secondary	Change in airway inflammatory markers (differential cell count, exhaled nitric oxide and airway cytokines) over study period		week 0 and week 6	No
Secondary	Change in lung function: Spirometry - forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC)		week 0 (Start) and week 6 (End)	No
Secondary	Change on blood pressure over study period		Week 0 (start) and Week 6 (end)	No
Secondary	Change in Liver function tests		Week 0 (start) and Week 6 (End)	Yes
Secondary	Change in creatine phosphokinase (CPK) over study period		Week 0 (start) and Week 6(End)	Yes
Secondary	Change in Handgrip strength over study period		Week 0 (start) and Week 6 (end)	No
Secondary	Change in blood desmosine over study period		Week 0 (Start) and Week 6 (end)	No
Secondary	Change in circulating matrix metalloproteinase over study period		Week 0 (start) and Week 6 (end)	No
Secondary	Baseline arterial stiffness (aortic pulse wave velocity)		Week 0	No
Secondary	Baseline airway (differential cell count, exhaled nitric oxide and cytokines)and circulating inflammatory status (cytokines)		Week 0	No
Secondary	Baseline matrix metalloproteinase in airway and blood		Week 0	No