Comparing the Effects of Cognitive Training and Physical Exercise on Cognition, Cerebral Autoregulation and Cerebral Vasoreactivity in Men and Women With Heart Failure

Aging Clinical Trial

— ReCARDIO  

Official title:

Comparing the Effects of Cognitive Training and Physical Exercise on Cognition, Cerebral Autoregulation and Cerebral Vasoreactivity in Men and Women With Heart Failure

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04970888
• Other study ID #: MP-33-2018-2406
• Status: Recruiting
• Phase: N/A
• Start date: September 1, 2021
• Est. completion date: September 1, 2025

Study information

• Verified date: November 2023
• Source: Montreal Heart Institute
• Contact: Louis Bherer, PhD
• Phone: +1 514-374-1480
• Email: louis.bherer[@]umontreal.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The objective of this project is to assess the effects of combined physical exercise and cognitive training interventions on cognitive and brain health in patients with heart failure (HF). Also, the role of sex on the effects of the interventions will be assessed.

Description:

Cognitive impairment (CI) affects up to 50% of patients with heart failure (HF), and is associated with high mortality rates, poor quality of life, reduced functional capacities, and an overwhelming economic burden in Western countries. Non-pharmacological strategies could help enhance cognition in HF patients with CI. Combined physical exercise and cognitive training interventions have recently shown promising enhancement effects on cognition in patients with cardiovascular risk factors and mild cognitive impairment. The effects of combined interventions have never been tested in HF. The main objective is to assess the effects of combined physical exercise and cognitive training interventions on cognition in patients with HF. Secondary objectives include: to characterize baseline and intervention-related changes in cerebral autoregulation and vasoreactivity and to assess the role of sex on the effects of the interventions. Two-hundred and sixteen participants (36 men and 36 women/group) with stable HF regardless of aetiology and LVEF will take part in this study. All participants will have signed a written consent form before taking part in the study. Patients will be stratified according to sex and LVEF (FEVG < 40% et FEVG > 40%), and will be randomly assigned to one of the 3 following study arms: 1) Combined physical exercise and cognitive training; 2) Physical exercise alone; and 3) Usual medical care.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 216
• Est. completion date: September 1, 2025
• Est. primary completion date: September 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

Inclusion Criteria:

• Age = 60 years old
• Stable chronic HF on maximally tolerated background treatment for at least 2 months (stable therapy with ACE-I, ARBs and MRA for at least 2 months), regardless of LVEF
• with no limitation of physical activity in ordinary physical activity (i.e. NYHA class I), moderate symptoms (i.e. NYHA class II) or marked limitation in activity (i.e. NYHA class III)
• Able to perform cognitive and physical training.

Exclusion Criteria:

• Acute cardiovascular event 1 month prior to randomization, including emergency visit or hospitalization for decompensated HF, acute myocardial infarction, stroke, and transient ischemic attack
• Planned cardiovascular intervention within 6 months (implantation of any cardiac device, cardiac revascularization, heart transplantation)
• Severe exercise intolerance
• Contraindications for exercise testing (e.g., uncorrected severe aortic or carotid stenosis, severe pulmonary hypertension, severe non-revascularizable coronary disease including left main coronary stenosis, significant myocardial ischemia or arrhythmia during low-intensity exercise, acute HF)
• Severe respiratory disease
• Non-cardiopulmonary limitation to exercise (e.g., arthritis, claudication or any peripheral neurological disease including other neurodegenerative diseases such as disabling Parkinson)
• Uncontrolled diabetes or untreated thyroid dysfunction
• Current or recent malignancy with life expectancy < 1 year
• Chronic hemodialysis or peritoneal dialysis
• Unable to read the informed consent form or unable to understand the oral explanations provided by the assessor.

Related Conditions & MeSH terms

• Aging
• Chronic Heart Failure
• Heart Failure

Intervention

Other:
• Cognitive training
The cognitive training will involve attention control training and memory training, with thrice-weekly 30-min sessions. Two of these sessions will involve computer or tablet-based attentional control training targeting dual-tasking, updating and working memory, as well as inhibition and switching. Difficulty of cognitive training will be tailored to participants' performances. The remaining session will consist of memory training. Participants will be instructed mnemotechnic, as well as be taught about memory in aging in general.
• Exercise training
Participants will follow a 20-week physical training program, with 60-min thrice-weekly trainings. The training sessions will start with a 5-min warm-up, followed by an aerobic training (20 min) after which 20-min of resistance/muscular training will take place. The program will end with a 10-min cool-down. Training will be adapted to individuals' baseline capacity as measured by the baseline cardiorespiratory test. For home-training sessions, participants will have access to a complete exercise training program. A certified kinesiologist will supervise trainings. With the Heart rate sensor Polar H10, all the characteristics of the activities will be recorded (type of the activity, intensity, heart rate, duration). A kinesiologist will call participants every week to ensure the smooth running of the exercises training sessions and individualize the care according to the patient's level.
• Usual care
All patients will receive usual care and be treated according to evidence-based treatments. This will include optimal medical therapy, systematic information regarding dietary and fluid management, and a recommendation for regular physical activity consistent with the latest update of the Canadian Cardiovascular Society Guidelines for the Management of Heart Failure. Moreover, patients who benefit from a prescription for a cardiovascular rehabilitation program will be able to follow it, but they will not receive other forms of intervention for the duration of the study.

Locations

Country	Name	City	State
Canada	Preventive medicine and physical activity centre (centre EPIC), Montreal Heart Institute	Montreal	Quebec

Sponsors (3)

Lead Sponsor	Collaborator
Montreal Heart Institute	Canadian Institutes of Health Research (CIHR), The Montreal Health Innovations Coordinating Center (MHICC)

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in cardiorespiratory fitness	Maximum incremental cardiopulmonary exercise test (VO2 max (ml.kg.min)	Baseline and post-intervention at 6 months
Other	Change in 6-min walking test performance	maximum distance performed in 6 minutes (distance, m)	Baseline and post-intervention at 6 months
Other	Change in upper limb muscle strength	Grip strength test score (kg).	Baseline and post-intervention at 6 months
Other	Change in quality of life	score on the 23 items of the Kansas City Cardiomyopathy Questionnaire (KCCQ)	Baseline and post-intervention at 6 months
Other	Change in perceived self care behaviour	European Heart Failure Self-care Behaviour Scale (EHFScB-9) will be completed. This self-reported questionnaire assesses the adherence to different self-care behaviours (e.g., eating low-salt diet, etc.).	Baseline and post-intervention at 6 months
Other	Change in anxiety	State-Trait Anxiety Inventory questionnaire (Score ranges from 20-80, with a higher score indicating higher anxiety).	Baseline and post-intervention at 6 months
Other	Change in depressive symptoms	Geriatric Depression Scale questionnaire (Score ranges from 0-30, with a higher score indicating larger depressive symptomatology).	Baseline and post-intervention at 6 months
Other	Change in sleep quality	Pittsburgh Sleep Quality Index questionnaire (Score ranges from 0-21, with a higher score indicating worse sleep quality). symptomatology).	Baseline and post-intervention at 6 months
Other	Cognitive reserve	Rami and colleagues' cognitive reserve questionnaire (Scale ranges from 0-26, with a higher score indicating a greater cognitive reserve).	Baseline
Other	Genotyping data	genotyping data that include the APOE gene	baseline
Other	Change in NT-pro-BNP	NT-pro-BNP (ng/L)	Baseline and post-intervention at 6 months
Other	Change in high-sensitive Troponin T	hsTnT (ng/mL)	Baseline and post-intervention at 6 months
Primary	Change in general cognitive functioning	Montreal Cognitive Assessment (0-30 score, with a higher score indicating a better cognitive functioning).	Baseline and post-intervention at 6 months
Primary	Change in processing speed	Validated remote version of neuropsychological tests and iPad tests (Composite Z-score).	Baseline and post-intervention at 6 months
Primary	Change in executive functions	Validated remote version of neuropsychological tests and iPad tests (Composite Z-score).	Baseline and post-intervention at 6 months
Primary	Change in episodic memory	Validated remote version of neuropsychological tests (Composite Z-score).	Baseline and post-intervention at 6 months
Secondary	Change in cerebral autoregulation - frontal cortical region	Variations of prefrontal cortical oxygen saturation (rSO2, [HbO]/([HbO]+[HbR])) will be measured by Near Infrared Spectroscopy (NIRS), as a surrogate of cortical blood flow. Variations of continuous peripheral blood pressure (mm Hg) will be simultaneously measured by plethysmography at the finger. Autoregulation indices (unitless) will be derived from the correlation between variations of oxygen saturation measures and variations of peripheral blood pressure.	Baseline and post-intervention at 6 months
Secondary	Change in cerebral autoregulation - middle cerebral arteries	Variations of cerebral blood flow velocity (cm/s) at the level of the middle cerebral artery will be measured by Transcranial Doppler (TCD). Variations of continuous peripheral blood pressure (mm Hg) will be simultaneously measured by plethysmography at the finger. Autoregulation indices (unitless) will be derived from the correlation between variations of cerebral blood flow measures and variations of peripheral blood pressure.	Baseline and post-intervention at 6 months
Secondary	Change in cerebral vasoreactivity - prefrontal cortex	Cerebral VasoReactivity (CVR, % change per mm Hg of PaCO2) will be measured using NIRS in the prefrontal region.	Baseline and post-intervention at 6 months
Secondary	Change in cerebral vasoreactivity - middle cerebral arteries	Cerebral VasoReactivity (CVR, % change per mm Hg of PaCO2) will be measured using TCD in the middle cerebral arteries.	Baseline and post-intervention at 6 months
Secondary	Change in cerebral pulsatility - cortical frontal region	Pulsatility will be measured as the normalized difference of relative near-infrared light intensity changes between systole and diastole, using NIRS in the prefrontal cortical region.	Baseline and post-intervention at 6 months
Secondary	Change in cerebral pulsatility - middle cerebral arteries	Pulsatility will be measured as the normalized difference of relative blood flow velocities between systole and diastole, using TCD in the middle cerebral arteries	Baseline and post-intervention at 6 months
Secondary	Change in cerebral activity	Significant changes in brain activity evoked by a N-back task relative to baseline will be assessed by t-statistics maps, computed from variations of [HbO] and [HbR] measured by NIRS at the prefrontal cortex.	Baseline and post-intervention at 6 months