Exercise and Brain in Coronary Heart Disease

Coronary Heart Disease Clinical Trial

— Heart-Brain  

Official title:

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT06214624
• Other study ID #: 1776-N21
• Status: Enrolling by invitation
• Phase: N/A
• Start date: April 19, 2022
• Est. completion date: June 2024

Study information

• Verified date: January 2024
• Source: Universidad de Granada
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 90
• Est. completion date: June 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Coronary Heart Disease
• Heart Diseases
• Myocardial Ischemia

Intervention

Behavioral:
• Two types of exercise interventions
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.

Locations

Country	Name	City	State
Spain	Sport and Health University Research Institute (iMUDS), Technological Health Park, University of Granada	Granada

Sponsors (6)

Lead Sponsor	Collaborator
Universidad de Granada	Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Centro de Investigación Mente, Cerebro y Comportamiento (CIMCYC), Hospital Clinico Universitario San Cecilio, Instituto Mixto Universitario Deporte y Salud (iMUDS), University Hospital Virgen de las Nieves

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in blood brain barrier (BBB) permeability	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.	Baseline and 12 weeks
Other	Change in brain morphology	MRI (magnetic resonance imaging) will measure brain morphology including volume, area, cortical thickness, and shapes by a T1-weighted MPRAGE structural sequence.	Baseline and 12 weeks
Other	Change in white matter structure	MRI (magnetic resonance imaging) will measure white matter structure and lesions by diffusion weighted acquisition sequence.	Baseline and 12 weeks
Other	Change in brain function	MRI (magnetic resonance imaging) will measure brain function during resting state. Measures of brain activity and brain connectivity will be calculated.	Baseline and 12 weeks
Other	Change in blood-based neurology biomarkers	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.	Baseline and 12 weeks
Other	Change in saliva-based neurology biomarkers	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.	Baseline and 12 weeks
Other	Hemodynamic vascular changes	Hemodynamic vascular parameters will be measured using ultrasound echography (i.e. carotid intima-media thickness).	Baseline and 12 weeks
Other	Hemodynamic cardiac changes	Cardiac parameters will be measured using ultrasound echography (i.e. ejection fraction, cardiac volumes, and cardiac output)	Baseline and 12 weeks
Other	Hemodynamic transcranial changes	Hemodynamic transcranial parameters will be measured using ultrasound echography (i.e. Doppler diastolic-systolic velocity).	Baseline and 12 weeks
Other	Change in general muscular strength	The maximum isometric strength of the hand and forearm muscles measured with the handgrip test (Kg) will be used to determine general muscular strength.	Baseline and 12 weeks
Other	Change in lower body muscular strength	Muscular strength in lower body will be assessed using the chair stand test (number of repetitions).	Baseline and 12 weeks
Other	Change in upper body muscular strength	Muscular strength in upper body will be assessed using the arm curl test (number of repetitions).	Baseline and 12 weeks
Other	Change in physical function	Senior Fitness Test (including the 6-min walking test) will assess overall physical functioning and z-scores will be calculated.	Baseline and 12 weeks
Other	Change in depression	Depressive symptoms will be assessed using the Global Deterioration Scale, the Health Survey Short Form (SF-36) and the Hospital Anxiety and Depression Scale.	Baseline and 12 weeks
Other	Change in anxiety	Anxiety will be assessed using the Health Survey Short Form (SF-36) and the Hospital Anxiety and Depression Scale.	Baseline and 12 weeks
Other	Change in stress outcomes	Stress outcomes will be assessed using the Perceived Stress Scale.	Baseline and 12 weeks
Other	Change in loneliness	Loneliness will be assessed using the UCLA Loneliness Scale.	Baseline and 12 weeks
Other	Change in self-esteem outcomes	Self-esteem will be assessed using the Rosenberg Self-Esteem Scale.	Baseline and 12 weeks
Other	Change in social support outcomes	Social support will be assessed using the Social Provisions Scale.	Baseline and 12 weeks
Other	Change in health-related quality of life	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.	Baseline and 12 weeks
Other	Change in physical activity	Physical activity will be measured using the accelerometer Axivity AX, and a self-reported questionnaire based on the Global Physical Activity Questionnaire.	Baseline and 12 weeks
Other	Change in sedentary behaviors	Sedentary behaviors will be measured using the accelerometer Axivity AX, and a self-reported questionnaire based on the Global Physical Activity Questionnaire.	Baseline and 12 weeks
Other	Change in sleep quality	Sleep quality will be measured using the accelerometer Axivity AX, and using the Pittsburgh Sleep Quality Index.	Baseline and 12 weeks
Other	Change in diet behaviors	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.	Baseline and 12 weeks
Other	Change in body mass index	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	Baseline and 12 weeks
Other	Change in lean mass	Lean mass (kg) will be assessed using a dual-energy x-ray absorptiometer (DXA) and a TANITA's Bioelectrical Impedance Analysis.	Baseline and 12 weeks
Other	Change in fat mass	Fat mass (kg) will be assessed using a dual-energy x-ray absorptiometer (DXA) and a TANITA's Bioelectrical Impedance Analysis.	Baseline and 12 weeks
Other	Change in bone mineral content and density	Bone mineral content and density (z-score) will be assessed using a dual-energy x-ray absorptiometer (DXA).	Baseline and 12 weeks
Other	Change in blood pressure	Systolic and diastolic blood pressure will be assessed by a blood pressure monitor. Central blood pressure will be also analyzed using the SphygmoCor XCEL	Baseline and 12 weeks
Other	Change in arterial stiffness	Arterial stiffness will be assessed using the pulse wave analysis and pulse wave velocity determined by the SphygmoCor XCEL	Baseline and 12 weeks
Other	Change in blood-based inflammatory biomarkers	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.	Baseline and 12 weeks
Other	Change in saliva-based inflammatory biomarkers	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).	Baseline and 12 weeks
Other	Change in blood-based cardiovascular biomarkers	Blood samples will be used to determine plasmatic concentrations of cardiovascular peripheral biomarkers including glucose, insulin, HDL and LDL cholesterol.	Baseline and 12 weeks
Other	Change in saliva-based cardiovascular biomarkers	Saliva samples will be used to determine plasmatic concentrations of cardiovascular peripheral biomarkers including glucose, insulin, HDL and LDL cholesterol.	Baseline and 12 weeks
Other	Change in epigenetics	Blood samples will be stored for epigenetic analyses.	Baseline and 12 weeks
Other	Change in gene expression	Blood samples will be stored for genetic analyses, including APOE and BDNF genotypes.	Baseline and 12 weeks
Other	Change in oral and gut microbiota	Saliva and fecal samples will be used to determine oral and gut microbiota including the most representative phyla (i.e., firmicutes, bacteroidetes, and proteobacteria)	Baseline and 12 weeks
Primary	Change in cerebral blood flow	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.	Baseline and 12 weeks
Secondary	Change cerebral vascularization	Cerebral vascularization will be measured using the magnetic resonance angiography TOF (Time-of-flight angiography).	Baseline and 12 weeks
Secondary	Change in executive function and general cognition	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.	Baseline and 12 weeks
Secondary	Change in cardiorespiratory fitness	Cardiorespiratory fitness will be assessed by a cardiorespiratory exercise test in a treadmill measuring gas exchange (treadmill time-to-exhaustion and VO2peak)	Baseline and 12 weeks