Cardiac Output and Brain Perfusion and Architecture During Exercise in Patients With Chronic Obstructive Pulmonary Disease (COPD) and Healthy, Age Matched Volunteers
Trial Snapshot
- Phase
- Not Applicable
- Sponsor
- University of Nottingham
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- Resting white and grey matter structural integrity
Study Overview
Brief Summary
Heart disease and conditions related to the blood vessels are responsible for a large proportion (over a quarter) of the deaths in people with chronic obstructive pulmonary disease (COPD). The changes can also affect the smaller smaller blood vessels within the body, in particular the brain and the kidneys. This might be related to how the heart pumps and if it is under any pressure. Investigations performed at the University in healthy older volunteers demonstrated how the blood flows in the brain and heart during exercise. Exercise gently puts the whole body under some pressure and therefore exposes any weaker areas.
In this study the investigators are hoping to find out what happens to the blood flow in the brain and in the heart in patients who have COPD when they exercise and in the resting state. This will be compared to people of a similar age with a similar smoking history but without COPD. This will be examined using state of the art magnetic resonance imaging (MRI) and will allow us to assess whether changes in structure and function are related to this altered blood flow.
Our hypothesis is that COPD will cause a larger change in blood flow during exercise compared to the healthy volunteers and that reduced cardiorespiratory fitness will be associated with increased age related structural within the brain.
Detailed Description
The aim is to recruit 20 participants with COPD, who will be compared to 10 age and gender matched controls who also have a smoking history. The investigators aim for this number to complete the components of the study and therefore may have to over-recruit if some people drop out or are not eligible. The study elements are feasible, as the work extends a previous research study in healthy volunteers.
This research trial will consist of a medical screening visit and three investigation study visits spaced ideally one week apart. The investigation visits will begin within 6 (ideally within 4) weeks of the medical screening visit. The total duration of the study and screening visits should be 12 weeks maximum for each participant.
Screening visit:
If the participant expresses an interest in the clinical trial and wants to take part they will be invited (at a convenient time for them) to attend a medical screening visit located at the Nottingham City hospital. Here the investigator will discuss the research trial and answer any questions or concerns they might have regarding the research trial. The participant, if willing, will then be required to sign a consent form so that the screening procedures can begin, which include:
- Blood sample: Approximately a 20ml sample (4 teaspoons) taken from their arm, for further investigation including full blood count (FBC), brain natriuretic peptide (BNP) and kidney function.
- Questionnaires: 5 different questionnaires that ask about symptoms and how they affect daily life, a physical activity questionnaire, quality of life questionnaire and a MRI safety questionnaire.
- Spirometry: A simple blowing test to assess the participants' breathing which is performed three times.
- 12 lead ECG.
- a hand grip dynamometer to assess muscle strength
- timed up and go test: a test used to measure gait speed, where participants are asked to get up from a chair and walking to 3 meters and back, whilst being timed.
- to wear a step counter (Sensewear armband) for a week during waking hours to record steps.
Study Design
- Study Type
- Observational
- Observational Model
- Case Control
- Time Perspective
- Cross Sectional
Eligibility Criteria
- Ages
- 60 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Patients aged 65-75 years old,
- •>10 pack years smoking,
- •FEV1/FVC <0.7 and FEV1<60% predicted (for COPD participants only)
- •Sedentary lifestyle (<10,000 steps per day)
- •Able to give informed consent
- •Able to read, understand and communicate coherently in English
Exclusion Criteria
- •Doctor diagnosis of ischaemic heart disease or heart failure
- •Doctor diagnosis of dementia or Alzheimers disease
- •History of previous cerebrovascular disease (stroke or TIA) or malignancy
- •Pregnancy or childbearing in the last 6 months
- •Maintenance oral corticosteroids in the past 6 months
- •Requirement for oral corticosteroids or antibiotics in the past 6 weeks
- •Active arthritis or other muscular condition limiting exercise
- •Surgical intervention in the last 12 weeks
- •Long term oxygen therapy requirement
- •Other formal current respiratory diagnosis
- •Thyroid disease
- •Diabetes Mellitus
- •Neurological or cognitive impairment
- •Significant physical disability
- •Any other conditions in addition to the above that the investigators consider may affect study measurements or safety
- •Inability to understand verbal and/or written explanation of the study requirements
Outcomes
Primary Outcomes
Resting white and grey matter structural integrity
Time Frame: up to 12 weeks
Grey and white matter volume (mm3) using the MRI MPRAGE sequences will be measured at rest
Cardiac structural integrity
Time Frame: up to 12 weeks
Myocardial strain (%) will be measured using the MRI cardiac tagging sequence at rest.
Cerebral blood flow
Time Frame: up to 12 weeks
Cerebral blood flow (ml/min) will be measured during rest, low level steady-state exercise and following cessation of exercise and compared between COPD and age and gender matched controls
Cerebral perfusion
Time Frame: up to 12 weeks
Cerebral artery perfusion (ml/100g/min) will be measured during rest, low level steady-state exercise and following cessation of exercise and compared between COPD and age and gender matched controls
Oxygen extraction fraction
Time Frame: up to 12 weeks
Oxygen extraction fraction (%) will be derived from the difference between arterial and venous cerebral oxygenation measured via TRUST MRI scan sequence during rest, low level steady-state exercise and following cessation of exercise and compared between COPD and age and gender matched controls
Aortic flow
Time Frame: up to 12 weeks
Aortic flow (ml/min) will be measured during rest, low level steady-state exercise and following cessation of exercise and compared between COPD and age and gender matched controls
Whole body fat and muscle quantification
Time Frame: up to 12 weeks
Whole body fat and muscle quantification (%) will be measured using the MRI whole body mdixon sequence at rest.
Secondary Outcomes
- Hand grip strength(1 week)
- Serum markers of inflammation for research purposes (likely to include IL-1, IL-6, and TNFα)(1 week)
- Muscle isometric strength (MVC)(up to 6 weeks)
- Physical activity level (IPAQ Physical activity questionnaire)(1 week)
- Hospital anxiety and depression scale (HADS)(1 week)
- Muscle isokinetic fatigue(up to 6 weeks)
- Montreal Cognitive Assessment (MoCA) cognition level(1 week)
- Quality of life (SGRQ)(1 week)
- Timed up and go test(1 week)
- Heart rate response to exercise(up to 6 weeks)