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COPDREFLEX-COPDNCT04138563

Cerebral and Cardiac Blood Flow During Exercise in Patients With COPD

An observational study of COPD and Cognitive Impairment, run by University of Nottingham at 1 site in United Kingdom.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 60 to 75 yearsHealthy volunteers can take part
Conditions the study is for
COPD, Cognitive Impairment
How many people
30 participants
Where
1 siteUnited Kingdom
Study dates
3 Jan 2019to 30 Sep 2020
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 60 to 75 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Study population: We are recruiting participants within the Nottinghamshire region. Specifically for patients with COPD, we are targeting outpatient respiratory clinics at the Nottingham University Hospitals Trust, inpatient admissions due to COPD exacerbation at the Nottingham City Hospital, pulmonary rehabilitation groups and respiratory focus groups within Nottingham and patients on the Nottingham Respiratory Research Unit database.

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 16Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site, 1 recruiting
  • NIHR Nottingham BRC Respiratory Theme, University of Nottingham and NUH Trust

    Nottingham, Nottinghamshire, NG5 1PB

    Ayushman Gupta, 01158231702, mszag4@exmail.nottingham.ac.uk

    Recruiting

Other trials in United Kingdom

About this study

Official title: Cardiac Output and Brain Perfusion and Architecture During Exercise in Patients With Chronic Obstructive Pulmonary Disease (COPD) and Healthy, Age Matched Volunteers

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.

Read the 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.

Provided the ECG, step count (<10,000 steps) and other screening elements are ok, the participant will proceed to Study visit 1.

Strength and exercise test protocol:

The participant will be required to abstain from strenuous exercise for the 48 hours prior to the visit and also from alcohol and caffeine for 24 hours prior. Upon arrival they will perform a knee extension exercise so we can establish the muscle strength in the legs, specifically 3 maximal knee extensions with a 30 second rest in between. We will also measure fatigue by dong 20 extensions after a short break.

After a break they will then undergo an exercise test using an MRI compatible stepper device (Ergospect Cardiostepper) whilst in a supine position. This has been adapted to be similar to how they will exercise in the MRI scanner. Volunteers will start off stepping at a frequency of 65-70 steps a minute at the minimum workload and every 3 minutes get gradually a little harder until exhaustion is reached. Heart rate at rest and in response to exercise will be measured using a heart monitor. Participants will be given the option to have their expired gases also measured during exercise using a face mask, though this is not necessary if not tolerated. In the final minute of each workload we will take a finger prick test to measure the gases in the patients blood. A 3 lead ECG and oxygen saturation probe will be attached during exercise as safety measures and the protocol will be halted if oxygen saturation falls below 80% or if any relevant rhythm abnormalities are seen on the ECG trace.

The second study visit will be used to confirm the exercise and strength parameters measured in the first study visit.

MRI protocol:

A series of scans of the brain and heart will be taken at rest and then whilst stepping on the stepper machine within the MRI. The exercise will be at a steady state low level intensity determined by calculating the workload at which a fraction of maximum heart rate was achieved during first 2 study visits.

The MRI scan itself will take about ¾ hour but upto 2 hours is allowed for preparation and introducing the scan to the participant. The scanner is quite noisy and so the participant will wear ear defenders during the scan. Because the scanner is built around a large magnet, the participant will be instructed to remove all metal from their body, including jewellery. There is no radiation involved.

Keywords
Exercise, Magnetic Resonance Imaging, Cerebrovascular physiology, Cardiovascular physiology, Supine ergometric stepper
Medical subject headings
Pulmonary Disease, Chronic Obstructive, Cognitive Dysfunction, Motor Activity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT04138563
Study groupRoleWhat they receive
CaseParticipants with a pack year history of more than 10 pack years, diagnosed with COPD who have FEV1/FVC ratio of less than 0.7 AND FEV1 predicted value less than or equal to 60%.
ControlParticipants without a diagnosis of COPD who have a smoking history of more than 10 pack years

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Resting white and grey matter structural integrity

    Grey and white matter volume (mm3) using the MRI MPRAGE sequences will be measured at rest

    Measured: up to 12 weeks

  2. Cardiac structural integrity

    Cardiac output (L/min) will be measured using the MRI sequence (Short axis Cine) at rest.

    Measured: up to 12 weeks

  3. Cardiac structural integrity

    Cardiac fibrosis (%) will be measured using the MRI MOLLI T1 sequence at rest.

    Measured: up to 12 weeks

  4. Cardiac structural integrity

    Myocardial strain (%) will be measured using the MRI cardiac tagging sequence at rest.

    Measured: up to 12 weeks

  5. Whole body fat and muscle quantification

    Whole body fat and muscle quantification (%) will be measured using the MRI whole body mdixon sequence at rest.

    Measured: up to 12 weeks

  6. Aortic flow

    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

    Measured: up to 12 weeks

  7. Cerebral blood flow

    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

    Measured: up to 12 weeks

  8. Cerebral perfusion

    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

    Measured: up to 12 weeks

  9. Oxygen extraction fraction

    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

    Measured: up to 12 weeks

Secondary outcomes (10)
  1. Muscle isometric strength (MVC)

    Isometric muscle torque of the quadriceps (Nm) assessed using the cybex dynamometer

    Measured: up to 6 weeks

  2. Muscle isokinetic fatigue

    Fatiguability test of the quadriceps (Nm) assessed using the cybex dynamometer

    Measured: up to 6 weeks

  3. Quality of life (SGRQ)

    Assessed using the St Georges Respiratory Questionnaire. min value: 0, max value: 84, higher score means worse outcome

    Measured: 1 week

  4. Physical activity level (IPAQ Physical activity questionnaire)

    Assessed using the International Physical activity questionnaire. min value: 0, max value: 66000, higher score means better outcome

    Measured: 1 week

  5. Montreal Cognitive Assessment (MoCA) cognition level

    Assessed using the Montreal cognitive assessment questionnaire. min value: 0, max value: 30, higher score means better outcome

    Measured: 1 week

  6. Hospital anxiety and depression scale (HADS)

    min value: 0, max value: 21, higher score means worse outcome

    Measured: 1 week

  7. Hand grip strength

    Composite of hand grip strength (Kg), measured by a hand held dynamometer,

    Measured: 1 week

  8. Timed up and go test

    Timed up and go test (seconds) will be measured to assess degree of frailty.

    Measured: 1 week

  9. Serum markers of inflammation for research purposes (likely to include IL-1, IL-6, and TNFα)

    Blood test

    Measured: 1 week

  10. Heart rate response to exercise

    Heart rate response (Beats per minute) will be measured at rest and during incremental exercise to assess cardio-respiratory fitness.

    Measured: up to 6 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Oct 2019
  2. Study start3 Jan 2019
  3. Primary completion30 Sep 2020 (estimated)
  4. Study completion30 Sep 2020 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Case-control
Time perspective
Cross-sectional
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04138563
Sponsor's protocol ID
18063
Acronym
REFLEX-COPD
Status last verified
Oct 2019
First submitted
17 Oct 2019
Last updated
30 Oct 2019
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • McGarvey LP, John M, Anderson JA, Zvarich M, Wise RA; TORCH Clinical Endpoint Committee. Ascertainment of cause-specific mortality in COPD: operations of the TORCH Clinical Endpoint Committee. Thorax. 2007 May;62(5):411-5. doi: 10.1136/thx.2006.072348. Epub 2007 Feb 20.

    PubMed 17311843
  • Sabit R, Bolton CE, Edwards PH, Pettit RJ, Evans WD, McEniery CM, Wilkinson IB, Cockcroft JR, Shale DJ. Arterial stiffness and osteoporosis in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2007 Jun 15;175(12):1259-65. doi: 10.1164/rccm.200701-067OC. Epub 2007 Mar 15.

    PubMed 17363772
  • John M, Hussain S, Prayle A, Simms R, Cockcroft JR, Bolton CE. Target renal damage: the microvascular associations of increased aortic stiffness in patients with COPD. Respir Res. 2013 Mar 5;14(1):31. doi: 10.1186/1465-9921-14-31.

    PubMed 23497267
  • Blair SN, Kohl HW 3rd, Paffenbarger RS Jr, Clark DG, Cooper KH, Gibbons LW. Physical fitness and all-cause mortality. A prospective study of healthy men and women. JAMA. 1989 Nov 3;262(17):2395-401. doi: 10.1001/jama.262.17.2395.

    PubMed 2795824
  • Erickson KI, Leckie RL, Weinstein AM. Physical activity, fitness, and gray matter volume. Neurobiol Aging. 2014 Sep;35 Suppl 2:S20-8. doi: 10.1016/j.neurobiolaging.2014.03.034. Epub 2014 May 14.

    PubMed 24952993

Questions about this trial

What is this clinical trial studying?

An observational study of COPD and Cognitive Impairment, run by University of Nottingham at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 30 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Ayushman Gupta (01158231702, mszag4@exmail.nottingham.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Resting white and grey matter structural integrity (time frame: up to 12 weeks). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04138563, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2019.

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