Back to resultsThe Effect of Statins in Patients With Chronic Obstructive Pulmonary Disease (COPD)
Primary Purpose
Chronic Obstructive Pulmonary Disease
Status
Completed
Phase
Phase 4
Locations
United Kingdom
Study Type
Interventional
Intervention
Simvastatin
Lactose tablet
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Obstructive Pulmonary Disease
Eligibility 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.
Sites / Locations
- Nottingham Respiratory Biomedical Research Unit
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Active Comparator
Arm Label
Lactose tablet
Simvastatin 20mg
Arm Description
Outcomes
Primary Outcome Measures
Change in arterial stiffness as measured by aortic pulse wave velocity (PWV) over study period
Aortic Pulse wave velocity (Sphygmocor, Atcor)
Secondary Outcome Measures
Change in Circulating Inflammatory Mediators over study period
Change in distance (metres)walked on 6 minute walking test
together with pre- and post-walk oxygen saturations
Change in blood total cholesterol, triglycerides, HDL and LDL over study period
Change in airway inflammatory markers (differential cell count, exhaled nitric oxide and airway cytokines) over study period
Change in lung function: Spirometry - forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC)
Change on blood pressure over study period
Change in Liver function tests
Change in creatine phosphokinase (CPK) over study period
Change in Handgrip strength over study period
Change in blood desmosine over study period
Change in circulating matrix metalloproteinase over study period
Baseline arterial stiffness (aortic pulse wave velocity)
Baseline airway (differential cell count, exhaled nitric oxide and cytokines)and circulating inflammatory status (cytokines)
Baseline matrix metalloproteinase in airway and blood
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01151306
Brief Title
The Effect of Statins in Patients With Chronic Obstructive Pulmonary Disease (COPD)
Official Title
The Cardiovascular and Inflammatory Effects of Statin Therapy in Patients With COPD
Study Type
Interventional
2. Study Status
Record Verification Date
March 2014
Overall Recruitment Status
Completed
Study Start Date
June 2010 (undefined)
Primary Completion Date
April 2013 (Actual)
Study Completion Date
August 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Nottingham
4. Oversight
Data Monitoring Committee
No
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Obstructive Pulmonary Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
70 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Lactose tablet
Arm Type
Placebo Comparator
Arm Title
Simvastatin 20mg
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Simvastatin
Intervention Description
Simvastatin 20mg once daily (in the evening) for 6 weeks
Intervention Type
Drug
Intervention Name(s)
Lactose tablet
Intervention Description
One tablet taken each evening for 6 weeks
Primary Outcome Measure Information:
Title
Change in arterial stiffness as measured by aortic pulse wave velocity (PWV) over study period
Description
Aortic Pulse wave velocity (Sphygmocor, Atcor)
Time Frame
Week 0 (start) and week 6 (end)
Secondary Outcome Measure Information:
Title
Change in Circulating Inflammatory Mediators over study period
Time Frame
Week 0 (Start) and week 6 (End)
Title
Change in distance (metres)walked on 6 minute walking test
Description
together with pre- and post-walk oxygen saturations
Time Frame
week 0 (start) and week 6 (end)
Title
Change in blood total cholesterol, triglycerides, HDL and LDL over study period
Time Frame
week 0 (Start) and week 6 (End)
Title
Change in airway inflammatory markers (differential cell count, exhaled nitric oxide and airway cytokines) over study period
Time Frame
week 0 and week 6
Title
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)
Title
Change on blood pressure over study period
Time Frame
Week 0 (start) and Week 6 (end)
Title
Change in Liver function tests
Time Frame
Week 0 (start) and Week 6 (End)
Title
Change in creatine phosphokinase (CPK) over study period
Time Frame
Week 0 (start) and Week 6(End)
Title
Change in Handgrip strength over study period
Time Frame
Week 0 (start) and Week 6 (end)
Title
Change in blood desmosine over study period
Time Frame
Week 0 (Start) and Week 6 (end)
Title
Change in circulating matrix metalloproteinase over study period
Time Frame
Week 0 (start) and Week 6 (end)
Title
Baseline arterial stiffness (aortic pulse wave velocity)
Time Frame
Week 0
Title
Baseline airway (differential cell count, exhaled nitric oxide and cytokines)and circulating inflammatory status (cytokines)
Time Frame
Week 0
Title
Baseline matrix metalloproteinase in airway and blood
Time Frame
Week 0
10. Eligibility
Sex
All
Minimum Age & Unit of Time
45 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Facility Information:
Facility Name
Nottingham Respiratory Biomedical Research Unit
City
Nottingham
ZIP/Postal Code
NG5 1PB
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
25673981
Citation
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.
Results Reference
derived
Learn more about this trial
The Effect of Statins in Patients With Chronic Obstructive Pulmonary Disease (COPD)
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