Effects of ROFLUMILAST on Subclinical Atherosclerosis in Chronic Obstructive Pulmonary Disease (COPD) (ELASTIC)
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|ClinicalTrials.gov Identifier: NCT01630200|
Recruitment Status : Completed
First Posted : June 28, 2012
Results First Posted : April 12, 2019
Last Update Posted : April 12, 2019
Chronic obstructive pulmonary disease is associated with a low grade systemic inflammatory process. Systemic inflammation is hypothesized to maintain cardiovascular morbidity and mortality in COPD. Early changes of vascular integrity can be detected via markers of subclinical atherosclerosis.
Selective Inhibition of phosphodiesterase subtype 4 describes a promising therapeutic option in COPD with beneficial impact on lung function and exacerbation rate. Moreover, an anti-inflammatory effect of phosphodiesterase-4 inhibition was confirmed by recent data.
The aim of this study is to assess the effects of the phosphodiesterase-4 inhibitor Roflumilast on firstly surrogates of subclinical atherosclerosis and secondly markers of systemic inflammation in the peripheral circulation of patients with stable chronic obstructive pulmonary disease.
|Condition or disease||Intervention/treatment||Phase|
|Chronic Obstructive Pulmonary Disease and Allied Conditions||Drug: Roflumilast Drug: Placebo||Phase 4|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||80 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Investigator, Outcomes Assessor)|
|Official Title:||Effects of ROFLUMILAST on Markers of Subclinical Atherosclerosis In Stable COPD; the ELASTIC-trial|
|Study Start Date :||May 2012|
|Actual Primary Completion Date :||January 2016|
|Actual Study Completion Date :||January 2016|
Active Comparator: Roflumilast
Active arm including patients who receive the study drug (500µg Roflumilast once daily)
Roflumilast coated tablet, 500µg oral application, once daily in the morning
Other Name: Daxas
Placebo Comparator: Placebo
Control arm including patients who receive the placebo tablet (once daily)
Placebo coated tablet (visually identical to 500µg Roflumilast tablet), oral application, once daily in the morning
- Change From Baseline in Carotid Femoral-Pulse Wave Velocity at Month 6 [ Time Frame: baseline, month 6 ]Carotid femoral-Pulse Wave Velocity (cf-PWV) will be measured non-invasively via applanation tonometry (AtCor Medical, Sydney, Australia). Wave propagation time will be calculated by the system software, using an ECG-gated reference frame. Aortic PWV is defined as the distance between two recording sites (i.e. common carotid- and femoral artery) divided by the wave propagation time.
- Change From Baseline in Reactive Hyperemia Index at Month 6 [ Time Frame: baseline, month 6 ]Endothelial dysfunction will be assessed by Flow Mediated Dilation via the Endopat device. This validated system measures the pulse wave amplitudes at the tip of both index fingers. The dominant arm will be occluded for 5 minutes by a sphygmomanometric cuff. After cuff deflation the pulse wave amplitude will be assessed to finally calculate the ratio of pulse wave amplitude before and after cuff-induced hyperemia. The so called reactive hyperemia index represents endothelial dysfunction at the level of conduit as well as resistance vessels.
- Change From Baseline in Augmentation Index at Month 6 [ Time Frame: baseline, month 6 ]The curve of the peripheral pressure wave will be recorded from the radial artery. Augmentation index (Aix) will be calculated from the generated central aortic pressure waveform via pulse wave analysis function. To correct for respective influences, Aix will be adjusted for a heart rate of 75 bpm. Appropriate intra observer validity will be assured via an operator index ≥ 80.
- Change From Baseline in Matrix Metalloproteinase-9 [ Time Frame: baseline, month 6 ]Circulating levels of Matrix Metalloproteinase-9 (MMP-9) will be quantified from venous blood samples via Enzyme-linked Immunosorbent Assay
- Change From Baseline in Asymmetric Dimethylarginine at Month 6 [ Time Frame: baseline, month 6 ]Circulating levels of Asymmetric dimethylarginine (ADMA) will be quantified from venous blood samples via Enzyme-linked Immunosorbent Assay
- Change From Baseline in Tumor Necrosis Factor-alpha at Month 6 [ Time Frame: baseline, month 6 ]Circulating levels of Tumor Necrosis Factor-alpha (TNF-alpha) will be quantified from venous blood samples via Enzyme-linked Immunosorbent Assay
- Change From Baseline in Forced Expiratory Volume in 1 Second at Month 6 [ Time Frame: baseline, month 6 ]Forced Expiratory Volume in 1 second (FEV1) will be measured via standardized Spirometry
- Change From Baseline in 6-Minute Walk Test at Month 6 [ Time Frame: baseline, month 6 ]6-Minute Walk Test (6MWT) will be assessed to quantify functional exercise capacity following the standardized protocol of the American Thoracic Society
- Change From Baseline in COPD Assessment Test at Month 6 [ Time Frame: baseline, month 6 ]COPD Assessment Test (CAT) will be assessed to quantify patients disease related symptoms and to measure the impact of COPD on a patient's life, and how this changes over time. CAT is a standardised and validated patient questionaire comprising 8 distinct questions about different COPD-related symptoms. Each symptom is quantified by the patient on a numeric scale ranging from 0 to 5. Each symptom gives a number of points quantified as interval data without decimal places. The 8 different numbers of points are added to a total number expressed as the final points of the CAT score. The minimum achievable number of points is 0 and the maximum achievable number of points is 40. Higher values provide high symptoms and worse outcome, lower values provide low symptoms and better outcome.
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): NCT01630200
|Deparment for Respiratory and Critical Care Medicine, Otto Wangner Hospital|
|Vienna, Austria, 1140|
|Principal Investigator:||Otto C Burghuber, M.D.||Department for Respiratory and Critical Care Medicine, Otto Wagner Hospital, Vienna|