Novel Vascular Manifestations of Chronic Obstructive Pulmonary Disease (NOVASC COPD)

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.

Study Overview

• Status: Completed
• Conditions: COPD

• Study Type: Observational
• Enrollment (Actual): 55

Contacts and Locations

Study Locations

• United Kingdom
  • Avon
    • Bristol, Avon, United Kingdom, BS10 5NB
      • North Bristol NHS Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Stable COPD

Description

Inclusion Criteria:

1. Subjects must give their signed and dated written informed consent
2. Subjects must be aged >40 and ≤ 85
3. Subjects with a smoking history > 10 pack years.
4. COPD group: Subjects with a FEV/FVC <70%

Exclusion Criteria:

1. Resting oxygen saturations <92% on room air.
2. Long term oxygen therapy
3. Recent exacerbation of COPD (4 weeks)
4. Ischaemic heart disease
5. Cerebrovascular disease
6. Uncontrolled hypertension
7. Diabetes mellitus
8. Hepatic failure
9. Neurological disease
10. Non-cured tumours
11. Obstructive sleep apnoea
12. Current of past alcohol/drug abuse
13. Known history of dementia
14. Visual or hearing impairment that precludes neuropsychological assessment
15. Neuropsychological tests undertaken outside the study
16. Pregnant women or women who are lactating
17. Known alpha 1 anti-trypsin deficiency as a cause of their COPD
18. History of psychiatric disorders, or other conditions that will impact on the validity of their consent or interfere with compliance to perform study procedures.
19. Contra indication to MRI scanning -

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
COPD; Stable, Non hypoxaemic, without history of vascular disease
Healthy smokers; Age matched, smokers without COPD

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Inflammatory Markers	Fibrinogen, C reacive Protein, IL-6	upto 4 weeks

Collaborators and Investigators

• Sponsor: North Bristol NHS Trust
• Investigators: Principal Investigator: James W Dodd, MB ChB PhD, University of Bristol

Publications and helpful links

General Publications

• McKay GJ, McCarter RV, Hogg RE, Higbee DH, Bajaj MK, Burrage DR, Ruickbie S, Baker EH, Jones PW, Dodd JW. Simple non-mydriatic retinal photography is feasible and demonstrates retinal microvascular dilation in Chronic Obstructive Pulmonary Disease (COPD). PLoS One. 2020 Jan 10;15(1):e0227175. doi: 10.1371/journal.pone.0227175. eCollection 2020.

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): July 1, 2016

Study Registration Dates

• First Submitted: November 29, 2013
• First Submitted That Met QC Criteria: February 7, 2014
• First Posted (Estimate): February 12, 2014

Study Record Updates

• Last Update Posted (Actual): June 28, 2018
• Last Update Submitted That Met QC Criteria: June 26, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: COPD; Cerebrovascular disease; Cognitive Function; Aortic Stiffness; MRI Brain
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: 3251