Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Nottingham
ClinicalTrials.gov Identifier:
NCT01151306
First received: June 21, 2010
Last updated: March 21, 2014
Last verified: March 2014
  Purpose

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 Intervention Phase
Chronic Obstructive Pulmonary Disease
Drug: Simvastatin
Drug: Lactose tablet
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Cardiovascular and Inflammatory Effects of Statin Therapy in Patients With COPD

Resource links provided by NLM:


Further study details as provided by University of Nottingham:

Primary Outcome Measures:
  • Change in arterial stiffness as measured by aortic pulse wave velocity (PWV) over study period [ Time Frame: Week 0 (start) and week 6 (end) ] [ Designated as safety issue: No ]
    Aortic Pulse wave velocity (Sphygmocor, Atcor)


Secondary Outcome Measures:
  • Change in Circulating Inflammatory Mediators over study period [ Time Frame: Week 0 (Start) and week 6 (End) ] [ Designated as safety issue: No ]
  • Change in distance (metres)walked on 6 minute walking test [ Time Frame: week 0 (start) and week 6 (end) ] [ Designated as safety issue: No ]
    together with pre- and post-walk oxygen saturations

  • Change in blood total cholesterol, triglycerides, HDL and LDL over study period [ Time Frame: week 0 (Start) and week 6 (End) ] [ Designated as safety issue: No ]
  • Change in airway inflammatory markers (differential cell count, exhaled nitric oxide and airway cytokines) over study period [ Time Frame: week 0 and week 6 ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • Change on blood pressure over study period [ Time Frame: Week 0 (start) and Week 6 (end) ] [ Designated as safety issue: No ]
  • Change in Liver function tests [ Time Frame: Week 0 (start) and Week 6 (End) ] [ Designated as safety issue: Yes ]
  • Change in creatine phosphokinase (CPK) over study period [ Time Frame: Week 0 (start) and Week 6(End) ] [ Designated as safety issue: Yes ]
  • Change in Handgrip strength over study period [ Time Frame: Week 0 (start) and Week 6 (end) ] [ Designated as safety issue: No ]
  • Change in blood desmosine over study period [ Time Frame: Week 0 (Start) and Week 6 (end) ] [ Designated as safety issue: No ]
  • Change in circulating matrix metalloproteinase over study period [ Time Frame: Week 0 (start) and Week 6 (end) ] [ Designated as safety issue: No ]
  • Baseline arterial stiffness (aortic pulse wave velocity) [ Time Frame: Week 0 ] [ Designated as safety issue: No ]
  • Baseline airway (differential cell count, exhaled nitric oxide and cytokines)and circulating inflammatory status (cytokines) [ Time Frame: Week 0 ] [ Designated as safety issue: No ]
  • Baseline matrix metalloproteinase in airway and blood [ Time Frame: Week 0 ] [ Designated as safety issue: No ]

Estimated Enrollment: 70
Study Start Date: June 2010
Study Completion Date: August 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   45 Years to 80 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01151306

Locations
United Kingdom
Nottingham Respiratory Biomedical Research Unit
Nottingham, United Kingdom, NG5 1PB
Sponsors and Collaborators
University of Nottingham
  More Information

No publications provided

Responsible Party: University of Nottingham
ClinicalTrials.gov Identifier: NCT01151306     History of Changes
Other Study ID Numbers: 09105
Study First Received: June 21, 2010
Last Updated: March 21, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Diseases
Simvastatin
Anticholesteremic Agents
Antimetabolites
Enzyme Inhibitors
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hypolipidemic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014