Novel Vascular Manifestations of Chronic Obstructive Pulmonary Disease

Study Overview
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Brief Summary
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Cognitive impairment is a known consequence of cerebral small-vessel disease. Moderate to severe cognitive impairment has been shown in up to 60% of certain individuals with COPD and is likely to profoundly influence an individual's ability to manage their disease. In addition to cerebral small vessel damage and cognitive dysfunction, other organs such as the heart, kidneys, and retina are likely to be susceptible to small-vessel damage in COPD. Several large population studies have shown that COPD is a significant independent risk factor for myocardial infarction, with the effect most marked in early, mild disease. We propose to compare non-invasive MR brain imaging of white matter microstructure (diffusion tensor), cerebral perfusion (arterial spin labelling) and accumulated cerebral small vessel disease (cerebral microbleeds), in COPD patients to smokers without COPD. In addition we plan to explore mechanisms of cerebral small vessel disease in COPD by looking for associations between arterial stiffness, end organ vascular damage and cognitive function.

Official Title
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Novel Vascular Manifestations of Chronic Obstructive Pulmonary Disease

Conditions
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COPD

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must give their signed and dated written informed consent Subjects must be aged >40 and ≤ 85 Subjects with a smoking history > 10 pack years. COPD group: Subjects with a FEV/FVC <70% Exclusion Criteria: Resting oxygen saturations <92% on room air. Long term oxygen therapy Recent exacerbation of COPD (4 weeks) Ischaemic heart disease Cerebrovascular disease Uncontrolled hypertension Diabetes mellitus Hepatic failure Neurological disease Non-cured tumours Obstructive sleep apnoea Current of past alcohol/drug abuse Known history of dementia Visual or hearing impairment that precludes neuropsychological assessment Neuropsychological tests undertaken outside the study Pregnant women or women who are lactating Known alpha 1 anti-trypsin deficiency as a cause of their COPD History of psychiatric disorders, or other conditions that will impact on the validity of their consent or interfere with compliance to perform study procedures. Contra indication to MRI scanning -

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| COPD<br>Stable, Non hypoxaemic, without history of vascular disease | |
| Healthy smokers<br>Age matched, smokers without COPD | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fractional Anisotropy | MRI Diffusion Imaging - measure of cerebral white matter microstructure | upto 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Aortic Pulse Wave Velocity | Aortic stiffness | upto 4 weeks | 
| MRI Cerebral Perfusion - ASL |  | upto 4 weeks | 
| Cerebral Microbleeds |  | upto 4 weeks | 
| Cognitive Function | Montreal Cognitive Assessment | upto 4 weeks | 
| Cardiac MRI | LV & RV Mass | upto 4 weeks | 
| FEV1 % predicted |  | upto 4 weeks | 
| Arterial Oxygen Saturation |  | upto 4 weeks | 
| Retinal Photography | Retinal Arterial Narrowing | upto 4 weeks | 
| Micro-albuminuria | Spot urine albumin sample mg/l (milligram albumin per litre of urine) | upto 4 weeks | 
| Health Status | COPD Assessment Test (CAT score) 0-40 | upto 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD, Cognitive Function, MRI Brain, Aortic Stiffness, Cerebrovascular disease