Skip to main content
OpenTrials
Completed

NCT Number: NCT06214624

Exercise and Brain in Coronary Heart Disease

The Heart-Brain project is a randomized controlled trial designed to examine the effects of two different exercise programs of 12-week duration: 1) aerobic high intensity interval training (HIIT), and 2) aerobic HIIT plus resistance training, on brain health and other outcomes in coronary heart disease patients.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Coronary Heart Disease Arterial Occlusive Diseases Arteriosclerosis Behavior Cardiovascular Diseases Coronary Artery Disease Coronary Disease Heart Diseases Motor Activity Myocardial Ischemia Vascular Diseases

Age range

50 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Sport and Health University Research Institute (iMUDS), Technological Health Park, University of Granada

Granada, 18007, Spain

About this study

Patients with coronary heart disease (CHD) has higher risk of developing dementia, cognitive impairment, and mental disorders. There is, therefore, a need to identify effective and sustainable initiatives to avoid or attenuate cognitive and mental health declines in these patients, and in this context, physical exercise can play a major role. The overall objective of the present project is to investigate the effects of exercise on brain health outcomes in CHD patients. The Heart-Brain project is a single-blinded, exercise-based randomized controlled trial. We will run a three-arms trial with a waiting-list control group, and two intervention groups that will receive two different supervised exercise programs: 1) aerobic high intensity interval training (HIIT) and 2) a combination of aerobic HIIT plus resistance training. The study will be conducted in 90 patients with CHD who meet the eligibility criteria indicated below.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Men and women aged between 50 and 75 years old, both inclusive (*Contingency plan: increase the range to 40-75 if we have difficulties to get the study sample)
  • Must have stable coronary heart disease (phase III), proven by invasive coronary angiography or CT with at least one coronary lesion > 50%.
  • Able to speak and read fluent Spanish.
  • Live in Granada city or surrounding areas (able to come to evaluations and exercise program)
  • Living in community during the study (i.e. independent home, non-assisted living facilities)
  • Ejection fraction ≥ 45%.
  • Functional grade I-II according to the New York Heart Association (NYHA) scale.
  • Sinus rhythm.
  • Stable optimal medical treatment (3 or more drugs at the determined by a cardiologist).
  • Physically inactive, considering: 1) not meeting the WHO recommendations in both the aerobic and strength part, and 2) not to be participating in a planned and structured exercise program at least 3 days per week and for more than 3 months. Both conditions must be met to be included. Note: going for a walk will not be considered an exclusion reason.
  • Classified as cognitively normal according to Stics-m

Exclusion criteria

  • Used of assisted walking devices.
  • Acute coronary syndrome in the last year, coronary surgery, or percutaneous intervention in the last 6 months.
  • Treatment for any type of cancer in the last 2 years.
  • Severe hospitalization in the intensive care unit in the last 6 months.
  • Current psychiatric diagnosis (visit to psychiatrist and drug treatment prescription in the last year), including major depression and history of psychiatric illness (schizophrenia, bipolar disorder, hallucinations).
  • Grade III obesity.
  • Diagnosis of neurological or cerebrovascular disorder (e.g. stroke).
  • Medical contraindication for inclusion in an exercise program.
  • Diabetes with uncontrolled glycemia.
  • Resting blood pressure > 180/110.
  • Chest pain with exertion or changes in the ST segment suggestive of severe ischemia during ergometry.
  • Severe inducible ischemia
  • Functional capacity in ergometry (<5 METS).
  • Obstructive left main artery disease (significant disease > 50%)
  • Unstable angina
  • Uncontrolled cardiac arrhythmia
  • Presence of metal implants (e.g., pacemaker or implantable cardioverter-defibrillator-ICD) not compatible with MRI (reported during the phone screening)
  • Paroxysmal or persistent atrial fibrillation with episodes in the last 6 months.
  • Moderate to severe pulmonary hypertension.
  • Acute endocarditis, myocarditis, or pericarditis.
  • Moderate to severe valve disease (grade 3-4)
  • Acute pulmonary embolism, or deep vein thrombosis.
  • Aortic dissection
  • High-grade heart block or complete left bundle branch block or altered basal electrocardiogram with difficulties to interpret in exercise testing.
  • Hypertrophic obstructive cardiomyopathy.
  • Retinopathy.
  • Severe autonomic or peripheral neuropathy.
  • Acute systemic illness or fever.
  • Acute or chronic renal failure (estimated glomerular filtration rate < 30 mL/min)
  • Pulmonary fibrosis or interstitial disease (respiratory failure or severe COPD confirmed by pneumological study).
  • Recent treatment for alcohol or substance abuse.
  • Claustrophobia.
  • Any surgery or medical intervention planned during the study period.
  • Plans to participate or current participation in other studies that might interferes with this study.
  • Current pregnancy or intention to get pregnant during the study period

Treatment and study plan

Two types of exercise interventions

Behavioral
  • HIIT. 3 times/week. This consists of a 4x4 HIIT (preferably in treadmill), 4 intervals of 4min at high intensity (85-95% HRmax) and 3 intervals of 3min of active resting at ~70% HRmax in between. All sessions including 10 min of warming-up and 10min of cooling down, resulting in 45min sessions. The first 2 weeks will progress from moderate-intensity training to HIIT for a better adaptation and acceptability of the program.
  • HIIT + resistance. 3 times/week. The aerobic part consists of a 3x4 HIIT (preferably in treadmill), 3 intervals of 4min at high intensity (85-95% HRmax) and 2 intervals of 3min of active resting (~70% HRmax) in between. The resistance part consists of 2 series of an 8-exercise circuit (combination of upper and lower body exercises using elastic bands and body weight) with a ratio of 20sec of effort - 40sec of resting. Sessions will have 5min of warming up in the treadmill and 5min of cooling down walking in the gym, comprising a total of 45min sessions.

Primary outcomes

  1. Change in cerebral blood flow

    Time frame: Baseline and 12 weeks

    The main outcome is the change in global cerebral blood flow from baseline to 12 weeks. Cerebral blood flow will be measured using the magnetic resonance imaging technique of TGSE-pCASL (turbo gradient spin echo-pseudo continuous arterial spin labeling). Additionally, regional cerebral blood flow will be determined in a voxel-wise analysis to measure local perfusion.

Secondary outcomes

  1. Change cerebral vascularization

    Time frame: Baseline and 12 weeks

    Cerebral vascularization will be measured using the magnetic resonance angiography TOF (Time-of-flight angiography).

  2. Change in executive function and general cognition

    Time frame: Baseline and 12 weeks

    A comprehensive neuropsychological battery will assess several domains of executive function: working memory, cognitive flexibility and inhibitory control, and an executive function score will be computed and used as main behavioral outcome . Additionally, the general cognition will be assessed by the MOCA (MONTREAL COGNITIVE ASSESSMENT) test.

  3. Change in cardiorespiratory fitness

    Time frame: Baseline and 12 weeks

    Cardiorespiratory fitness will be assessed by a cardiorespiratory exercise test in a treadmill measuring gas exchange (treadmill time-to-exhaustion and VO2peak)

Other outcomes

  1. Change in blood brain barrier (BBB) permeability

    Time frame: Baseline and 12 weeks

    BBB permeability will be operationally measured by using a recently developed neuroimaging technique that measures water exchange across the BBB using 3D diffusion-prepared arterial spin labelled perfusion MRI.

  2. Change in brain morphology

    Time frame: Baseline and 12 weeks

    MRI (magnetic resonance imaging) will measure brain morphology including volume, area, cortical thickness, and shapes by a T1-weighted MPRAGE structural sequence.

  3. Change in white matter structure

    Time frame: Baseline and 12 weeks

    MRI (magnetic resonance imaging) will measure white matter structure and lesions by diffusion weighted acquisition sequence.

  4. Change in brain function

    Time frame: Baseline and 12 weeks

    MRI (magnetic resonance imaging) will measure brain function during resting state. Measures of brain activity and brain connectivity will be calculated.

  5. Change in blood-based neurology biomarkers

    Time frame: Baseline and 12 weeks

    Blood samples will be used to determine plasmatic concentration of peripheral neurology biomarkers including brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF) and cathepsin B (CTSB), as well as novel neurodegenerative biomarkers based on new evidence up to the time of the analysis.

  6. Change in saliva-based neurology biomarkers

    Time frame: Baseline and 12 weeks

    Saliva samples will be used to determine concentration of peripheral neurology biomarkers including brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF) and cathepsin B (CTSB), as well as novel neurodegenerative biomarkers based on new evidence up to the time of the analysis.

  7. Hemodynamic vascular changes

    Time frame: Baseline and 12 weeks

    Hemodynamic vascular parameters will be measured using ultrasound echography (i.e. carotid intima-media thickness).

  8. Hemodynamic cardiac changes

    Time frame: Baseline and 12 weeks

    Cardiac parameters will be measured using ultrasound echography (i.e. ejection fraction, cardiac volumes, and cardiac output)

  9. Hemodynamic transcranial changes

    Time frame: Baseline and 12 weeks

    Hemodynamic transcranial parameters will be measured using ultrasound echography (i.e. Doppler diastolic-systolic velocity).

  10. Change in general muscular strength

    Time frame: Baseline and 12 weeks

    The maximum isometric strength of the hand and forearm muscles measured with the handgrip test (Kg) will be used to determine general muscular strength.

  11. Change in lower body muscular strength

    Time frame: Baseline and 12 weeks

    Muscular strength in lower body will be assessed using the chair stand test (number of repetitions).

  12. Change in upper body muscular strength

    Time frame: Baseline and 12 weeks

    Muscular strength in upper body will be assessed using the arm curl test (number of repetitions).

  13. Change in physical function

    Time frame: Baseline and 12 weeks

    Senior Fitness Test (including the 6-min walking test) will assess overall physical functioning and z-scores will be calculated.

  14. Change in depression

    Time frame: Baseline and 12 weeks

    Depressive symptoms will be assessed using the Global Deterioration Scale, the Health Survey Short Form (SF-36) and the Hospital Anxiety and Depression Scale.

  15. Change in anxiety

    Time frame: Baseline and 12 weeks

    Anxiety will be assessed using the Health Survey Short Form (SF-36) and the Hospital Anxiety and Depression Scale.

  16. Change in stress outcomes

    Time frame: Baseline and 12 weeks

    Stress outcomes will be assessed using the Perceived Stress Scale.

  17. Change in loneliness

    Time frame: Baseline and 12 weeks

    Loneliness will be assessed using the UCLA Loneliness Scale.

  18. Change in self-esteem outcomes

    Time frame: Baseline and 12 weeks

    Self-esteem will be assessed using the Rosenberg Self-Esteem Scale.

  19. Change in social support outcomes

    Time frame: Baseline and 12 weeks

    Social support will be assessed using the Social Provisions Scale.

  20. Change in health-related quality of life

    Time frame: Baseline and 12 weeks

    Global, physical, and mental health-related quality of life will be self-reported using the Health Survey Short Form (SF-36), in which higher scores means a better health-related quality of life.

  21. Change in physical activity

    Time frame: Baseline and 12 weeks

    Physical activity will be measured using the accelerometer Axivity AX, and a self-reported questionnaire based on the Global Physical Activity Questionnaire.

  22. Change in sedentary behaviors

    Time frame: Baseline and 12 weeks

    Sedentary behaviors will be measured using the accelerometer Axivity AX, and a self-reported questionnaire based on the Global Physical Activity Questionnaire.

  23. Change in sleep quality

    Time frame: Baseline and 12 weeks

    Sleep quality will be measured using the accelerometer Axivity AX, and using the Pittsburgh Sleep Quality Index.

  24. Change in diet behaviors

    Time frame: Baseline and 12 weeks

    Diet behaviors will be self-reported using the 14-item Questionnaire of Mediterranean Diet Adherence (PREDIMED-14), and a self-reported question for supplements intake.

  25. Change in body mass index

    Time frame: Baseline and 12 weeks

    Body mass index (BMI) will be assessed using a dual-energy x-ray absorptiometer (DXA) and a TANITA's Bioelectrical Impedance Analysis. Weight and height will be combined to report BMI in kg/m^2

  26. Change in lean mass

    Time frame: Baseline and 12 weeks

    Lean mass (kg) will be assessed using a dual-energy x-ray absorptiometer (DXA) and a TANITA's Bioelectrical Impedance Analysis.

  27. Change in fat mass

    Time frame: Baseline and 12 weeks

    Fat mass (kg) will be assessed using a dual-energy x-ray absorptiometer (DXA) and a TANITA's Bioelectrical Impedance Analysis.

  28. Change in bone mineral content and density

    Time frame: Baseline and 12 weeks

    Bone mineral content and density (z-score) will be assessed using a dual-energy x-ray absorptiometer (DXA).

  29. Change in blood pressure

    Time frame: Baseline and 12 weeks

    Systolic and diastolic blood pressure will be assessed by a blood pressure monitor. Central blood pressure will be also analyzed using the SphygmoCor XCEL

  30. Change in arterial stiffness

    Time frame: Baseline and 12 weeks

    Arterial stiffness will be assessed using the pulse wave analysis and pulse wave velocity determined by the SphygmoCor XCEL

  31. Change in blood-based inflammatory biomarkers

    Time frame: Baseline and 12 weeks

    Blood samples will be used to determine plasmatic concentrations of inflammatory peripheral biomarkers including tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1beta), glucose, insulin, HDL and LDL cholesterol.

  32. Change in saliva-based inflammatory biomarkers

    Time frame: Baseline and 12 weeks

    Saliva samples will be used to determine saliva concentrations of inflammatory peripheral biomarkers including tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1beta).

  33. Change in blood-based cardiovascular biomarkers

    Time frame: Baseline and 12 weeks

    Blood samples will be used to determine plasmatic concentrations of cardiovascular peripheral biomarkers including glucose, insulin, HDL and LDL cholesterol.

  34. Change in saliva-based cardiovascular biomarkers

    Time frame: Baseline and 12 weeks

    Saliva samples will be used to determine plasmatic concentrations of cardiovascular peripheral biomarkers including glucose, insulin, HDL and LDL cholesterol.

  35. Change in epigenetics

    Time frame: Baseline and 12 weeks

    Blood samples will be stored for epigenetic analyses.

  36. Change in gene expression

    Time frame: Baseline and 12 weeks

    Blood samples will be stored for genetic analyses, including APOE and BDNF genotypes.

  37. Change in oral and gut microbiota

    Time frame: Baseline and 12 weeks

    Saliva and fecal samples will be used to determine oral and gut microbiota including the most representative phyla (i.e., firmicutes, bacteroidetes, and proteobacteria)

Sponsors and collaborators

Lead sponsor

Universidad de Granada

Other

Collaborators

  • Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición
  • Hospital Clinico Universitario San Cecilio
  • Instituto Mixto Universitario Deporte y Salud (iMUDS)
  • Research Center for Mind, Brain and Behavior, Spain
  • University Hospital Virgen de las Nieves

Registry information

Official study title

Effects of Exercise on Brain Health in Patients With Coronary Heart Disease: the Heart-Brain Randomized Controlled Trial

Acronym: Heart-Brain

Important dates

Study start
2022
Primary completion
2024
Study completion
2024
First posted
Jan 19, 2024
Registry last updated
May 4, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.