The main purpose of this study is to determine the effect of Losmapimod on blood vessels in patients with Chronic Obstructive Pulmonary Disease (COPD). Although COPD is a lung disease, it is also associated with an increased risk of cardiovascular disease (e.g. heart attacks and stroke). The investigators believe that this is a result of inflammation within the body, which damages the lining (endothelium) and walls of blood vessels. These changes can promote the development of fatty deposits within the walls of arteries (atherosclerosis) which can rupture and block arteries causing damage.
The study aims to enrol sufficient COPD subjects (stratified by fibrinogen level) so that 60 patients complete the study. Study patients will have a 50% chance of receiving either Losmapimod or Placebo. Patients will be expected to attend for up to 12 visits, over a 24 week period. The visits consist of an initial screening visit, and 2 pre-dose imaging visits to include a PET-CT scan and an optional MRI scan. The next 7 visits (at 2-4 weekly intervals) involve blood tests and safety evaluations. A number of procedures including heart tracings (ECGs), non-invasive vascular measurements and lung function tests at the start and at the end of the study. Repeat imaging with PET-CT and MRI will be performed at the end of the study and a follow-up visit. The purpose of the study is to see if the study medication has a beneficial effect on vascular function and structure. It is envisaged that this trial will help define more evolutionary biomarkers to focus on to help COPD patients in the future.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
72
One tablet of Losmapimod 7.5mg twice daily
One tablet twice daily
Cambridge University Hospitals NHS Foundation Trust
Cambridge, Cambridgeshire, United Kingdom
Royal Brompton & Harefield NHS Foundation Trust
London, London, United Kingdom
Vascular inflammation on FDG PET-CT
To determine the effect of Losmapimod in COPD patients on vascular structure and function as assessed by the change in Vascular inflammation as measured by FDG PET-CT
Time frame: Days 0 to Day 112
Endothelial function as measured by flow mediated dilatation
To determine the effect of Losmapimod in COPD patients on vascular structure and function as assessed by the change in endothelial function as measured by flow mediated dilatation
Time frame: Days 0 to Day 112
Arterial structure and plaque characteristics on MRI
To determine the effect of Losmapimod in COPD patients on vascular structure and function as assessed by the change in arterial structure and plaque characteristics as measured by MRI (MRI is an optional sub-study and analysis will be based on a sufficient number of datasets).
Time frame: Days 0 to Day 112
Lung inflammation on FDG PET-CT
To determine the effects of Losmapimod on the change in inflammation in lung tissue as assessed by FDG PET-CT
Time frame: Days 0 to 112
Fat inflammation on FDG PET-CT
To determine the effects of Losmapimod on the change in fat inflammation as assessed by FDG PET-CT
Time frame: Days 0 to 112
Arterial stiffness as measured by arterial tonometry
To determine the effects of Losmapimod on the change in arterial stiffness as measured by arterial tonometry
Time frame: Days 0 to 112
Blood biomarkers of systemic inflammation (Fibrinogen and high sensitivity CRP)
To determine the effects of Losmapimod on the change in blood biomarkers of inflammation such as Fibrinogen and high sensitivity CRP
Time frame: Days 0 to 112
Indices of lung function (6 minute walk test and sniff nasal inspiratory pressure)
To determine the effects of Losmapimod on the change in indices of lung function and physical performance as measured by 6 minute walk test and sniff nasal inspiratory pressure
Time frame: Days 0 to 112
Body composition and fat as assessed by Free fat mass index
To determine the effects of Losmapimod on the change in body composition and fat as measured by Free fat mass index
Time frame: Days 0 to 112
Number of adverse events as a measure of safety and tolerability
To determine the effects of Losmapimod on the number of adverse events as a measure of safety and tolerability
Time frame: Days 0 to 112
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