The Effects of Atorvastatin Treatment in COPD Patients

Rationale: Retrospective studies suggest that statins improve outcomes in COPD patients possibly as a result of an anti-inflammatory effect.

Objectives: To determine whether statins have an anti-inflammatory effect on the lungs of patients with COPD.

A controlled, parallel group study to compare the effects of Atorvastatin in comparison to placebo as an add-on treatment to Formoterol therapy in patients with mild to moderate COPD in group of 20 patients. All subjects will have spirometry, lung volumes, DLCO, SGRQ, 6MWD, serum lipids and hs-CRP measured before and after treatment. Bronchoscopy and transbronchial lung biopsy (TBB) will be carried out at baseline and after 12 weeks of treatment, and TBB specimens will be processed for histology, immunohistochemistry and microarray analysis.

Study Overview

• Status: Completed
• Conditions: COPD
• Intervention / Treatment: Drug: Atorvastatin; Drug: Formoterol; Drug: Lactose tablet

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 4

Contacts and Locations

Study Locations

• Poland
  • Bialystok, Poland, 15-540
    • Department of Lung Diseases and Tuberculosis, Medical University of Bialystok

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

. Written informed consent must be obtained before any assessment is performed. 2. Male and female adults aged ≥40 years, who have signed an Informed Consent Form prior to initiation of any study-related procedure.

3. Patients with moderate to very severe stable COPD (Stage II-IV) according to the GOLD guidelines.

4. Patients with a post-bronchodilator FEV1 < 80% of the predicted normal, and a post-bronchodilator FEV1/FVC < 0.70 at Visit 1.

5. Current or ex-smokers who have a smoking history of at least 10 pack years

Exclusion criteria

1. Pregnant or nursing (lactating) women
2. Women of child-bearing potential, unless they are using effective methods of contraception during dosing of study treatment. 5. 3. Patients with a clinically significant abnormality at Visit 1.

4. Patients with a clinically relevant laboratory abnormality at Visit 1 5. Patients with a history of malignancy of any organ system (including lung cancer).

6. Patients contraindicated for treatment with statins 7. Patients unable to perform acceptable spirometry and lung volumes procedures.

8. Patients who have had a COPD exacerbation that required treatment with antibiotics and/or oral corticosteroids and/or hospitalization in the 6 weeks prior to Visit 1.

9. Patients who have had a respiratory tract infection within 4 weeks prior to Visit 1.

10. Patients requiring oxygen therapy (>15 hr/day) on a daily basis for chronic hypoxemia 11. Patients with any history of asthma or onset of symptoms prior to age 40 years.

12. Patients with concomitant pulmonary disease, (e.g. lung fibrosis, sarcoidosis, interstitial lung disease, pulmonary hypertension, tuberculosis).

13. Patients with primary bronchiectasis. 14. Patients with a diagnosis of α-1 anti-trypsin deficiency. 15. Patients with pulmonary lobectomy or lung volume reduction surgery or lung transplantation.

16. Patients participating in or planning to participate in the active phase of a supervised pulmonary rehabilitation program during the study.

17. Patients receiving any medications in the class listed in Table 5.1 18. Use of other investigational drugs within 30 days prior to visit 1.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Atorvastatin; 40 mg of Atorvastatin once daily as add-on to Formoterol only 12 weeks therapy.	Drug: Atorvastatin; Other Names: Sortis 40, manufactured by Godecke GmBH Mooswaldallee 1 790900; Freiburg, Germany; Drug: Formoterol; 12mcg of Foradil BID as maintenance COPD treatment in both treatment arms; Other Names: Foradil, Novartis,
Placebo Comparator: Lactose tablet; One tablet taken once a day as add-on treatment to Formoterol baseline 12 weeks therapy.	Drug: Formoterol; 12mcg of Foradil BID as maintenance COPD treatment in both treatment arms; Other Names: Foradil, Novartis,; Drug: Lactose tablet; One lactose tablet taken once a day as add-on treatment to Formoterol therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in CD45+ cells expression over study period	Change in CD45+ cells expression measured by immunohistochemistry in lung biopsy samples assessed before and after 12 weeks of treatment	12 weeks
Change in gene expression over study period	Change in gene expression measured in lung biopsy samples measured using microarrays before and after 12 weeks of treatment	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in health related quality of life over study period	Change in health related quality of life assessed by St. George's respiratory questionnaire before and after 12 weeks of treatment	12 weeks
Change in 6-Minute Walk Distance over study period	Change in 6-Minute Walk Distance measured according to 6-MWD protocol before and after 12 weeks of treatment	12 weeks
Change in intimal-medial thickness over study period	Change in intimal-medial thickness (IMT) measured in the common carotid artery (CCA) using a standard technique.	12 weeks
Change in hs-CRP over study period	Change in serum hs-C-reactive protein (hs-CRP) measured before and after 12 weeks of therapy	12 weeks
Change in total cholesterol, LDL and HDL-Cholesterol and triglycerides over study period	Change in total cholesterol, LDL and HDL-Cholesterol, and triglycerides measured before an after 12 weeks of therapy.	12 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in lung volumes over study period	Change in lung volumes measured using body plethysmography before and after 12 weeks of treatment	12 weeks
Change in FEV1 over study period	Change in FEV1 measured using spirometry before and after 12 weeks of treatment	12 weeks

Collaborators and Investigators

• Sponsor: Medical University of Bialystok
• Investigators: Principal Investigator: Robert M Mroz, MD, Medical University of Bialystok, Bialystok, Poland

Publications and helpful links

General Publications

• Mroz RM, Lisowski P, Tycinska A, Bierla J, Trzeciak PZ, Minarowski L, Milewski R, Lisowska A, Boros P, Sobkowicz B, Duszewska AM, Chyczewska E, Musial WJ, MacNee W. Anti-inflammatory effects of atorvastatin treatment in chronic obstructive pulmonary disease. A controlled pilot study. J Physiol Pharmacol. 2015 Feb;66(1):111-28.

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (Actual): April 1, 2013
• Study Completion (Actual): April 1, 2013

Study Registration Dates

• First Submitted: December 9, 2012
• First Submitted That Met QC Criteria: December 11, 2012
• First Posted (Estimate): December 12, 2012

Study Record Updates

• Last Update Posted (Estimate): April 23, 2013
• Last Update Submitted That Met QC Criteria: April 21, 2013
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Keywords: COPD; Atorvastatin; statins; COPD treatment; microarrays
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Antimetabolites; Adrenergic Agonists; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Atorvastatin; Formoterol Fumarate
• Other Study ID Numbers: 113-46-966; N N402 593440 (Other Identifier: Polish National Centre of Science)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No