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COPDPhase 4NCT00680641

Simvastatin in Chronic Obstructive Pulmonary Disease (COPD)

A Phase 4 study testing Simvastatin in people with COPD and Emphysema, run by University of East Anglia at 2 sites in United Kingdom.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 45 to 85 years
Conditions the study is for
COPD, Emphysema
What is being tested?
Simvastatin
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
20 participants
Where
2 sitesUnited Kingdom
Study dates
Apr 2008to Feb 2012
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 45 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 12Show fewer
  • 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.

Trial locations and contacts

2 sites in 1 country.

United Kingdom2 sites

  • CRTU University of East Anglia

    Norwich, Norfolk, NR47TJ

  • CRTU Norfolk and Norwich University Hospital

    Norwich, Norfolk, NR74UY

Other trials in United Kingdom

About this study

Official title: The Effects of Simvastatin in Patients With Chronic Obstructive Pulmonary Disease

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.

Read the 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.

Conditions
COPD, Emphysema
Being tested
Simvastatin, Placebo
Keywords
COPD, Emphysema, Simvastatin
Medical subject headings
Pulmonary Disease, Chronic Obstructive, Emphysema

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SimvastatinDrug

    40mg of Simvastatin once daily

  • PlaceboDrug

    40mg of placebo once daily

Study groups in NCT00680641
Study groupRoleWhat they receive
AActive comparatorSimvastatin 40mg
Receives: Drug: Simvastatin
BPlacebo comparatorPlacebo
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The difference in serum high sensitivity C-reactive protein (HsCRP) between simvastatin and placebo

    Measured: 4 checks over a four month period at 2 weeks, 10 weeks, 14 weeks and 22 weeks.

Secondary outcomes (7)

  1. The difference between treatment with simvastatin and placebo for Clinical COPD Questionnaire

    Measured: 4 months

  2. The difference between treatment with simvastatin and placebo for Spirometry - FEV1, FVC, FEV1/FVC ratio

    Measured: 4 months

  3. The difference between treatment with simvastatin and placebo for Induced sputum differential cell count

    Measured: 4 months

  4. The difference between treatment with simvastatin and placebo for Induced sputum mRNA for MMP and TIMPs

    Measured: 4 months

  5. The difference between treatment with simvastatin and placebo for Exhaled breath condensate 8-isoprostane concentration

    Measured: 4 Months

  6. The difference between treatment with simvastatin and placebo for Serum TNFa

    Measured: 4 months

  7. The difference between treatment with simvastatin and placebo for Cholesterol

    Measured: 4 Months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 May 2008 (estimated)
  2. Study startApr 2008
  3. Primary completionFeb 2011
  4. Study completionFeb 2012 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
20 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00680641
Sponsor's protocol ID
2007RESP06
Status last verified
Aug 2011
First submitted
16 May 2008
Last updated
5 Aug 2011
Results posted
No
Data monitoring committee
No

Publications

  • Hothersall E, McSharry C, Thomson NC. Potential therapeutic role for statins in respiratory disease. Thorax. 2006 Aug;61(8):729-34. doi: 10.1136/thx.2005.057976.

    PubMed 16877692

  • Soyseth V, Brekke PH, Smith P, Omland T. Statin use is associated with reduced mortality in COPD. Eur Respir J. 2007 Feb;29(2):279-83. doi: 10.1183/09031936.00106406. Epub 2006 Oct 18.

    PubMed 17050558

  • Hanefeld M, Marx N, Pfutzner A, Baurecht W, Lubben G, Karagiannis E, Stier U, Forst T. Anti-inflammatory effects of pioglitazone and/or simvastatin in high cardiovascular risk patients with elevated high sensitivity C-reactive protein: the PIOSTAT Study. J Am Coll Cardiol. 2007 Jan 23;49(3):290-7. doi: 10.1016/j.jacc.2006.08.054. Epub 2007 Jan 8.

    PubMed 17239709

  • Kevorkian L, Young DA, Darrah C, Donell ST, Shepstone L, Porter S, Brockbank SM, Edwards DR, Parker AE, Clark IM. Expression profiling of metalloproteinases and their inhibitors in cartilage. Arthritis Rheum. 2004 Jan;50(1):131-41. doi: 10.1002/art.11433.

    PubMed 14730609

  • Montuschi P. Exhaled breath condensate analysis in patients with COPD. Clin Chim Acta. 2005 Jun;356(1-2):22-34. doi: 10.1016/j.cccn.2005.01.012. Epub 2005 Mar 23.

    PubMed 15936301

  • Kasielski M, Nowak D. Long-term administration of N-acetylcysteine decreases hydrogen peroxide exhalation in subjects with chronic obstructive pulmonary disease. Respir Med. 2001 Jun;95(6):448-56. doi: 10.1053/rmed.2001.1066.

    PubMed 11421501

  • van der Molen T, Willemse BW, Schokker S, ten Hacken NH, Postma DS, Juniper EF. Development, validity and responsiveness of the Clinical COPD Questionnaire. Health Qual Life Outcomes. 2003 Apr 28;1:13. doi: 10.1186/1477-7525-1-13.

    PubMed 12773199

  • Pizzichini E, Pizzichini MM, Efthimiadis A, Evans S, Morris MM, Squillace D, Gleich GJ, Dolovich J, Hargreave FE. Indices of airway inflammation in induced sputum: reproducibility and validity of cell and fluid-phase measurements. Am J Respir Crit Care Med. 1996 Aug;154(2 Pt 1):308-17. doi: 10.1164/ajrccm.154.2.8756799.

    PubMed 8756799

  • Standardization of spirometry--1987 update. Statement of the American Thoracic Society. Am Rev Respir Dis. 1987 Nov;136(5):1285-98. doi: 10.1164/ajrccm/136.5.1285. No abstract available.

    PubMed 3674589

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Simvastatin in people with COPD and Emphysema, run by University of East Anglia at 2 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 5 Aug 2011. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00680641, which also lists 9 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Aug 2011.

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