Clinical trial NCT06214624: Exercise and Brain in Coronary Heart Disease
Official title: Effects of Exercise on Brain Health in Patients With Coronary Heart Disease: the Heart-Brain Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Coronary Heart Disease
Keywords: coronary artery disease
ischemic heart disease
exercise
HIIT
resistance training
brain
cognition
magnetic resonance imaging
Lead sponsor: Universidad de Granada
Sponsor class: OTHER
Collaborators: name: Instituto Mixto Universitario Deporte y Salud (iMUDS)
name: Centro de Investigación Mente, Cerebro y Comportamiento (CIMCYC)
name: University Hospital Virgen de las Nieves
name: Hospital Clinico Universitario San Cecilio
name: Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN)
First posted: 2024-01-19
Enrollment: 96
Sex: ALL
Minimum age (years): 50
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. 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)
2. Must have stable coronary heart disease (phase III), proven by invasive coronary angiography or CT with at least one coronary lesion \> 50%.
3. Able to speak and read fluent Spanish.
4. Live in Granada city or surrounding areas (able to come to evaluations and exercise program)
5. Living in community during the study (i.e. independent home, non-assisted living facilities)
6. Ejection fraction ≥ 45%.
7. Functional grade I-II according to the New York Heart Association (NYHA) scale.
8. Sinus rhythm.
9. Stable optimal medical treatment (3 or more drugs at the determined by a cardiologist).
10. 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.
11. Classified as cognitively normal according to Stics-m

Exclusion Criteria:

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

Primary outcomes:
measure: Change in cerebral blood flow
timeFrame: Baseline and 12 weeks
Secondary outcomes:
measure: Change cerebral vascularization
timeFrame: Baseline and 12 weeks
measure: Change in executive function and general cognition
timeFrame: Baseline and 12 weeks
measure: Change in cardiorespiratory fitness
timeFrame: Baseline and 12 weeks
Other outcomes:
measure: Change in blood brain barrier (BBB) permeability
timeFrame: Baseline and 12 weeks
measure: Change in brain morphology
timeFrame: Baseline and 12 weeks
measure: Change in white matter structure
timeFrame: Baseline and 12 weeks
measure: Change in brain function
timeFrame: Baseline and 12 weeks
measure: Change in blood-based neurology biomarkers
timeFrame: Baseline and 12 weeks
measure: Change in saliva-based neurology biomarkers
timeFrame: Baseline and 12 weeks
measure: Hemodynamic vascular changes
timeFrame: Baseline and 12 weeks
measure: Hemodynamic cardiac changes
timeFrame: Baseline and 12 weeks
measure: Hemodynamic transcranial changes
timeFrame: Baseline and 12 weeks
measure: Change in general muscular strength
timeFrame: Baseline and 12 weeks
measure: Change in lower body muscular strength
timeFrame: Baseline and 12 weeks
measure: Change in upper body muscular strength
timeFrame: Baseline and 12 weeks
measure: Change in physical function
timeFrame: Baseline and 12 weeks
measure: Change in depression
timeFrame: Baseline and 12 weeks
measure: Change in anxiety
timeFrame: Baseline and 12 weeks
measure: Change in stress outcomes
timeFrame: Baseline and 12 weeks
measure: Change in loneliness
timeFrame: Baseline and 12 weeks
measure: Change in self-esteem outcomes
timeFrame: Baseline and 12 weeks
measure: Change in social support outcomes
timeFrame: Baseline and 12 weeks
measure: Change in health-related quality of life
timeFrame: Baseline and 12 weeks
measure: Change in physical activity
timeFrame: Baseline and 12 weeks
measure: Change in sedentary behaviors
timeFrame: Baseline and 12 weeks
measure: Change in sleep quality
timeFrame: Baseline and 12 weeks
measure: Change in diet behaviors
timeFrame: Baseline and 12 weeks
measure: Change in body mass index
timeFrame: Baseline and 12 weeks
measure: Change in lean mass
timeFrame: Baseline and 12 weeks
measure: Change in fat mass
timeFrame: Baseline and 12 weeks
measure: Change in bone mineral content and density
timeFrame: Baseline and 12 weeks
measure: Change in blood pressure
timeFrame: Baseline and 12 weeks
measure: Change in arterial stiffness
timeFrame: Baseline and 12 weeks
measure: Change in blood-based inflammatory biomarkers
timeFrame: Baseline and 12 weeks
measure: Change in saliva-based inflammatory biomarkers
timeFrame: Baseline and 12 weeks
measure: Change in blood-based cardiovascular biomarkers
timeFrame: Baseline and 12 weeks
measure: Change in saliva-based cardiovascular biomarkers
timeFrame: Baseline and 12 weeks
measure: Change in epigenetics
timeFrame: Baseline and 12 weeks
measure: Change in gene expression
timeFrame: Baseline and 12 weeks
measure: Change in oral and gut microbiota
timeFrame: Baseline and 12 weeks
Locations:
city: Granada
country: Spain
facility: Sport and Health University Research Institute (iMUDS), Technological Health Park, University of Granada
Study officials:
affiliation: Department of Physical Education and Sports, Faculty of Sport Sciences, University of Granada, Spain
name: Francisco B Ortega, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Toval A, Solis-Urra P, Bakker EA, Sanchez-Aranda L, Fernandez-Ortega J, Prieto C, Alonso-Cuenca RM, Gonzalez-Garcia A, Martin-Fuentes I, Fernandez-Gamez B, Olvera-Rojas M, Coca-Pulido A, Bellon D, Sclafani A, Sanchez-Martinez J, Rivera-Lopez R, Herrera-Gomez N, Penafiel-Burkhardt R, Lopez-Espinosa V, Corpas-Perez S, Garcia-Ortega MB, Vega-Cordoba A, Barranco-Moreno EJ, Morales-Navarro FJ, Nieves R, Caro-Rus A, Amaro-Gahete FJ, Mora-Gonzalez J, Vidal-Almela S, Carlen A, Migueles JH, Erickson KI, Moreno-Escobar E, Garcia-Orta R, Esteban-Cornejo I, Ortega FB. Exercise and brain health in patients with coronary artery disease: study protocol for the HEART-BRAIN randomized controlled trial. Front Aging Neurosci. 2024 Aug 23;16:1437567. doi: 10.3389/fnagi.2024.1437567. eCollection 2024.
citation: Toval A, Bakker EA, Granada-Maia JB, Nunez de Arenas-Arroyo S, Solis-Urra P, Eijsvogels TMH, Esteban-Cornejo I, Martinez-Vizcaino V, Ortega FB. Exercise type and settings, quality of life, and mental health in coronary artery disease: a network meta-analysis. Eur Heart J. 2025 Jan 15:ehae870. doi: 10.1093/eurheartj/ehae870. Online ahead of print.