Cerebral and Cardiac Blood Flow During Exercise in Patients With COPD

NCT04138563 | Unknown

• 1 other identifier: 18063
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

COPD; Cognitive Impairment

Keywords

Exercise; Magnetic Resonance Imaging; Cerebrovascular physiology; Cardiovascular physiology; Supine ergometric stepper

Outcome Measures

Primary Outcomes (9)

• Resting white and grey matter structural integrity

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

  up to 12 weeks

• Cardiac structural integrity

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

  up to 12 weeks

• Cardiac structural integrity

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

  up to 12 weeks

• Cardiac structural integrity

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

  up to 12 weeks

• Whole body fat and muscle quantification

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

  up to 12 weeks

• 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

  up to 12 weeks

• 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

  up to 12 weeks

• 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

  up to 12 weeks

• 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

  up to 12 weeks

Secondary Outcomes (10)

• Muscle isometric strength (MVC)

  up to 6 weeks

• Muscle isokinetic fatigue

  up to 6 weeks

• Quality of life (SGRQ)

  1 week

• Physical activity level (IPAQ Physical activity questionnaire)

  1 week

• Montreal Cognitive Assessment (MoCA) cognition level

  1 week

Study Arms (2)

Case

Participants 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%.

Control

Participants without a diagnosis of COPD who have a smoking history of more than 10 pack years

Eligibility Criteria

• Age: 60 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

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.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Nottingham: lead

Study Sites (1)

NIHR Nottingham BRC Respiratory Theme, University of Nottingham and NUH Trust

Nottingham, Nottinghamshire, NG5 1PB, United Kingdom

RECRUITING

Related Publications (5)

• 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.

  PMID: 17311843 BACKGROUND

• 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.

  PMID: 17363772 BACKGROUND

• 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.

  PMID: 23497267 BACKGROUND

• 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.

  PMID: 2795824 BACKGROUND

• 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.

  PMID: 24952993 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood (plasma and serum) will be the only tissue collected. Upto 20 mls in total will be taken. some will be directly sent off for FBC, BNP and renal function. The rest of the serum will be aliquoted and stored for later research purposes.

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Cognitive Dysfunction; Motor Activity

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Behavior

Study Officials

• Charlotte Bolton

  NIHR Nottingham Biomedical Research Centre Respiratory theme, University of Nottingham

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ayushman Gupta

CONTACT

01158231702; mszag4@exmail.nottingham.ac.uk

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 17, 2019
• First Posted: October 24, 2019
• Study Start: January 3, 2019
• Primary Completion: September 30, 2020
• Study Completion: September 30, 2020
• Last Updated: October 30, 2019

Record last verified: 2019-10

Locations

GB (1)