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Simvastatin in Chronic Obstructive Pulmonary Disease (COPD)

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ClinicalTrials.gov Identifier: NCT00680641
Recruitment Status : Unknown
Verified August 2011 by University of East Anglia.
Recruitment status was:  Active, not recruiting
First Posted : May 20, 2008
Last Update Posted : August 5, 2011
Sponsor:
Information provided by:
University of East Anglia

Brief Summary:
To determine the effects of 2 months therapy with simvastatin 40mg once per day compared to placebo in a double-blind placebo-controlled study of patients with COPD.

Condition or disease Intervention/treatment Phase
COPD Emphysema Drug: Simvastatin Drug: Placebo Phase 4

Detailed Description:

Statins (HMG-Coenzyme A reductase inhibitors) are widely used clinically as lipid lowering drugs; however they have also been shown to exhibit anti-inflammatory and anti-oxidant properties(1). Recently published large retrospective cohort studies, in patients with chronic obstructive pulmonary disease (COPD), suggest that statins reduce mortality and COPD related admissions(2). Possible mechanisms of action include effects on cell adhesion molecules, changes in inflammatory mediator release, antioxidant effect and increased clearance of apoptoic cells. Simvastatin has been shown to reduce the development of smoking induced emphysema in rats with reductions in MMP-9 activity and simvastatin withdrawal leads to increased MMP levels in hypercholesterolaemic patients. Serum concentrations of TNFa and high sensitive C Reactive protein(3) (hs-CRP) are reduced with simvastatin therapy in patients with hypercholesterolaemia and risk of cardiovascular disease respectively. No clinical trial has directly evaluated the clinical effects of statins in patients with COPD in terms of induced sputum MMP profile, alveolar nitric oxide or pulmonary physiology.

We have modified our published method of RNA purification, developed to purify RNA from cartilage, tendon or synovium(4), to yield good quality RNA from sputum with relative simplicity and low cost. We have identified MMP-2, -9 and -14 in the sputum of healthy volunteers (unpublished pilot data) and will utilise this technique in the current study. Exhaled breath condensate (EBC) is completely non-invasive, requires no co-operation from individuals and provides information about a number of inflammatory and oxidation pathways. Markers of oxidative stress (8-isoprostane and hydrogen peroxide) and nitric oxide products can be measured in exhale breath condensate(5) and are related to disease activity in patients with COPD. Markers of oxidative stress increase in concentration in EBC during exacerbations of COPD are reduced after treatment with the antioxidant N-acetyl cysteine(6). Hydrogen peroxide is not stable and therefore 8-isoprostane is a preferable marker of oxidative stress unless the sample is measured on line.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: The Effects of Simvastatin in Patients With Chronic Obstructive Pulmonary Disease
Study Start Date : April 2008
Actual Primary Completion Date : February 2011
Estimated Study Completion Date : February 2012

Resource links provided by the National Library of Medicine

Drug Information available for: Simvastatin

Arm Intervention/treatment
Active Comparator: A
Simvastatin 40mg
Drug: Simvastatin
40mg of Simvastatin once daily

Placebo Comparator: B
Placebo
Drug: Placebo
40mg of placebo once daily




Primary Outcome Measures :
  1. The difference in serum high sensitivity C-reactive protein (HsCRP) between simvastatin and placebo [ Time Frame: 4 checks over a four month period at 2 weeks, 10 weeks, 14 weeks and 22 weeks. ]

Secondary Outcome Measures :
  1. The difference between treatment with simvastatin and placebo for Clinical COPD Questionnaire [ Time Frame: 4 months ]
  2. The difference between treatment with simvastatin and placebo for Spirometry - FEV1, FVC, FEV1/FVC ratio [ Time Frame: 4 months ]
  3. The difference between treatment with simvastatin and placebo for Induced sputum differential cell count [ Time Frame: 4 months ]
  4. The difference between treatment with simvastatin and placebo for Induced sputum mRNA for MMP and TIMPs [ Time Frame: 4 months ]
  5. The difference between treatment with simvastatin and placebo for Exhaled breath condensate 8-isoprostane concentration [ Time Frame: 4 Months ]
  6. The difference between treatment with simvastatin and placebo for Serum TNFa [ Time Frame: 4 months ]
  7. The difference between treatment with simvastatin and placebo for Cholesterol [ Time Frame: 4 Months ]


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Ages Eligible for Study:   45 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female, aged more than 45 years.
  • Physician labelled diagnosis of chronic obstructive pulmonary disease,emphysema or chronic bronchitis.
  • Smoker or ex-smoker with a pack year smoking history of greater than 20 pack years
  • FEV1 30-70% predicted
  • FEV1/FVC< 70%
  • Body Mass Index <25kg/m2

Exclusion Criteria:

  • 1. Cardiac or pulmonary disease other than chronic obstructive pulmonary disease.
  • Untreated hypothyroidism
  • Respiratory infection defined as fever, nasal/sinus congestion, fatigue, cough, antibiotic use or yellow/green sputum within 4 weeks prior to study.
  • Receiving current oral corticosteroid therapy or leukotriene modifying therapy.
  • Severe or uncontrolled co-morbid disease
  • History of atopy or asthma
  • Clinical history of bronchiectasis
  • Pregnancy or breastfeeding
  • Women of child-bearing potential, unless adequate contraception is used (ie contraceptive pill or double-barrier contraception - partner using condom and subject using spermicide, diaphragm, intra-uterine device or contraceptive sponge)
  • Unable to give written informed consent
  • Patients receiving a statin prior to entry into the study
  • Hypersensitivity to simvastatin or to any of the excipients.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00680641


Locations
United Kingdom
CRTU University of East Anglia
Norwich, Norfolk, United Kingdom, NR47TJ
CRTU Norfolk and Norwich University Hospital
Norwich, Norfolk, United Kingdom, NR74UY
Sponsors and Collaborators
University of East Anglia
Investigators
Principal Investigator: Andrew M Wilson, MD, MRCP (UK) Clinical Senior Lecturer, University of East Anglia

Publications:

Responsible Party: Dr Andrew M Wilson, University of East Anglia
ClinicalTrials.gov Identifier: NCT00680641     History of Changes
Other Study ID Numbers: 2007RESP06
First Posted: May 20, 2008    Key Record Dates
Last Update Posted: August 5, 2011
Last Verified: August 2011

Keywords provided by University of East Anglia:
COPD
Emphysema
Simvastatin

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