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

Sponsor

Montreal Heart Institute (Other)

Overall Status

Recruiting

CT.gov ID

NCT04970888

Collaborator

Canadian Institutes of Health Research (CIHR) (Other), The Montreal Health Innovations Coordinating Center (MHICC) (Other)

216

Enrollment

Location

Arms

Anticipated Duration (Months)

4.5

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Heart Failure Aging	Other: Cognitive training Other: Exercise training Other: Usual care	N/A

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

216 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

parallel assignment (1:1:1)parallel assignment (1:1:1)

Masking:

Double (Investigator, Outcomes Assessor)

Masking Description:

This clinical trial is a single-blinded study. Research personnel performing the outcome assessments and investigators will be blinded to group allocation.

Primary Purpose:

Prevention

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

Actual Study Start Date :

Sep 1, 2021

Anticipated Primary Completion Date :

Sep 1, 2025

Anticipated Study Completion Date :

Sep 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Combined Combined physical exercise and cognitive training. The combined intervention will include a cognitive training with aerobic and resistance exercises training, three sessions per week for 6 months. Participants will be allowed to perform cognitive and exercise training sessions either home-based or centre-based.	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. Other: 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. Other: 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.
Experimental: Exercise The physical exercises intervention will include aerobic and resistance exercises training, three sessions per week for 6 months. Participants will be allowed to perform exercise training sessions either home-based or centre-based.	Other: 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. Other: 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.
Active Comparator: Usual care Usual medical care with no interventions	Other: 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.

Arm

Intervention/Treatment

Experimental: Combined

Combined physical exercise and cognitive training. The combined intervention will include a cognitive training with aerobic and resistance exercises training, three sessions per week for 6 months. Participants will be allowed to perform cognitive and exercise training sessions either home-based or centre-based.

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.

Other: 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.

Other: 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.

Experimental: Exercise

The physical exercises intervention will include aerobic and resistance exercises training, three sessions per week for 6 months. Participants will be allowed to perform exercise training sessions either home-based or centre-based.

Other: Exercise training

Other: Usual care

Active Comparator: Usual care

Usual medical care with no interventions

Other: Usual care

Outcome Measures

Primary Outcome Measures

Change in general cognitive functioning [Baseline and post-intervention at 6 months]
Montreal Cognitive Assessment (0-30 score, with a higher score indicating a better cognitive functioning).
Change in processing speed [Baseline and post-intervention at 6 months]
Validated remote version of neuropsychological tests and iPad tests (Composite Z-score).
Change in executive functions [Baseline and post-intervention at 6 months]
Validated remote version of neuropsychological tests and iPad tests (Composite Z-score).
Change in episodic memory [Baseline and post-intervention at 6 months]
Validated remote version of neuropsychological tests (Composite Z-score).

Secondary Outcome Measures

Change in cerebral autoregulation - frontal cortical region [Baseline and post-intervention at 6 months]
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.
Change in cerebral autoregulation - middle cerebral arteries [Baseline and post-intervention at 6 months]
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.
Change in cerebral vasoreactivity - prefrontal cortex [Baseline and post-intervention at 6 months]
Cerebral VasoReactivity (CVR, % change per mm Hg of PaCO2) will be measured using NIRS in the prefrontal region.
Change in cerebral vasoreactivity - middle cerebral arteries [Baseline and post-intervention at 6 months]
Cerebral VasoReactivity (CVR, % change per mm Hg of PaCO2) will be measured using TCD in the middle cerebral arteries.
Change in cerebral pulsatility - cortical frontal region [Baseline and post-intervention at 6 months]
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.
Change in cerebral pulsatility - middle cerebral arteries [Baseline and post-intervention at 6 months]
Pulsatility will be measured as the normalized difference of relative blood flow velocities between systole and diastole, using TCD in the middle cerebral arteries
Change in cerebral activity [Baseline and post-intervention at 6 months]
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.

Other Outcome Measures

Change in cardiorespiratory fitness [Baseline and post-intervention at 6 months]
Maximum incremental cardiopulmonary exercise test (VO2 max (ml.kg.min)
Change in 6-min walking test performance [Baseline and post-intervention at 6 months]
maximum distance performed in 6 minutes (distance, m)
Change in upper limb muscle strength [Baseline and post-intervention at 6 months]
Grip strength test score (kg).
Change in quality of life [Baseline and post-intervention at 6 months]
score on the 23 items of the Kansas City Cardiomyopathy Questionnaire (KCCQ)
Change in perceived self care behaviour [Baseline and post-intervention at 6 months]
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.).
Change in anxiety [Baseline and post-intervention at 6 months]
State-Trait Anxiety Inventory questionnaire (Score ranges from 20-80, with a higher score indicating higher anxiety).
Change in depressive symptoms [Baseline and post-intervention at 6 months]
Geriatric Depression Scale questionnaire (Score ranges from 0-30, with a higher score indicating larger depressive symptomatology).
Change in sleep quality [Baseline and post-intervention at 6 months]
Pittsburgh Sleep Quality Index questionnaire (Score ranges from 0-21, with a higher score indicating worse sleep quality). symptomatology).
Cognitive reserve [Baseline]
Rami and colleagues' cognitive reserve questionnaire (Scale ranges from 0-26, with a higher score indicating a greater cognitive reserve).
Genotyping data [baseline]
genotyping data that include the APOE gene
Change in NT-pro-BNP [Baseline and post-intervention at 6 months]
NT-pro-BNP (ng/L)
Change in high-sensitive Troponin T [Baseline and post-intervention at 6 months]
hsTnT (ng/mL)

Eligibility Criteria

Criteria

Ages Eligible for Study:

60 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.