Exercise the Mind and Brain. A Multimodal Intervention in Stroke

Study Overview
=================
Brief Summary
-----------------
The main objective of MindFit Project is to develop an evidence-based multimodal investigation of combined non-pharmacological strategies in chronic stroke patients and clarify the neuroplasticity mechanisms underlying the benefits of physical exercise and mindfulness strategies combined with cognitive training on post-stroke recovery. The investigators have adopted a multidisciplinary and multimodal approach to provide a more integrative perspective using cognitive, social-psychological, biochemical, and neuroimaging measurements.

Detailed Description
-----------------
The MindFit Project is a multicentric, prospective, parallel, single-blinded, randomized controlled trial with a sample of 141 participants at 3 to 60 months after stroke. Participants are randomly allocated to one of three arms (through a simple randomizing procedure with a 1:1:1 ratio created with a random sequence generator software). The first group (n=47) receives computer-based cognitive training (CCT) combined with a multicomponent physical exercise program. The second group (n=47) receives CCT combined with mindfulness-based stress reduction therapy. Finally, the third group (n=47), as an active control group, receives only CCT. All interventions last 12 weeks. Within two weeks before the start of the interventions, and again at 3 months after completing the interventions, medical, cognitive, and physical assessments, neuroimaging, and biological samples collection are performed. The objectives of this project are: To examine the effects of multimodal interventions in a population of chronic stroke patients on various domains: cognition, emotion, physical health, and quality of life. To examine specific plasticity effects of each of the three interventions regarding structural and functional magnetic resonance imaging (MRI) and how these changes may contribute to cognitive and emotional benefits. To study the molecular mechanisms by which the different types of interventions influence cognitive, emotional and brain benefits. To study interventions-induced microbiome changes and to explain how these changes may induce inflammatory and immune responses that may contribute to cognitive, emotional and brain benefits. To determine the demographic, clinical and genetic factors that may modulate cognitive, emotional and brain changes: baseline cognitive status; baseline cerebral status (atrophy, total intracranial volume); sex; age, educational level, intelligence.

Official Title
-----------------
Effects of Combined Therapies of Physical Exercise, Mindfulness and Cognitive Stimulation on Cognition and Neuroplasticity in Chronic Stroke Patients: A Randomized Controlled Trial

Conditions
-----------------
Stroke

Intervention / Treatment
-----------------
* Behavioral: Multicomponent Physical Activity Program
* Behavioral: Mindfulness-Based Stress Reduction Program
* Behavioral: Computerized Cognitive Training


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Individuals aged 18-80 years old Ischemic or hemorrhagic stroke Stroke diagnoses between 3-60 months ago To have consent from a physician to engage in an exercise intervention Fluency in Catalan or Spanish (I.e., able to understand and speak) Accept to take part in the study and sign the informed consent according to the Declaration of Helsinki. Exclusion Criteria: Cognitive impairment (MMSE > 23) Severe aphasia (item 9 of the NIHSS scale ≥ 2) Severe sensory problems Other neurological conditions apart from stroke Severe pre-stroke psychiatric disorders (e.g., bipolar disorder, schizophrenia) History of alcohol or other toxic abuse Exclusion criteria only for MRI examination: Claustrophobia Medical device (e.g., pacemaker implants, stents) Other metal objects in the body

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 141 participants at 3 to 60 months after stroke are randomly allocated to one of three arms: The first group (n=47) receives computer-based cognitive training (CCT) combined with a multicomponent physical exercise program. The second group (n=47) receives CCT combined with mindfulness-based stress reduction therapy. Finally, the third group (n=47), as an active control group, receives only CCT.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Physical exercise & cognitive training group<br>The Physical exercise & cognitive training group receives a multicomponent physical exercise program combined with computer-based cognitive training. | Behavioral: Multicomponent Physical Activity Program<br>* The proposed physical exercise intervention follows the American College of Sports Medicine (ACSM, 2017) and the American Stroke Association (Billinger et al., 2014) recommendations for stroke patients. The five weekly 45-minute sessions are divided into (1) three sessions guided and supervised telematically by a physical exercise specialist and a physiotherapist; (2) and two autonomous exercise sessions. The supervised sessions include exercises to work aerobic capacity, muscle strength and endurance, flexibility, agility, and balance. The intensity of these exercises is prescribed individually according to each participant's initial level and are gradually increased as the program progresses. Participants are encouraged to walk at a similar intensity on autonomous physical exercise days as performed in the guided sessions (moderate intensity), based on the Borg scale of perceived exertion (Borg, 1982).<br>Behavioral: Computerized Cognitive Training<br>* An accredited neuropsychologist programs and supervises the computerized cognitive training through the Guttmann Neuropersonal Trainer (GNPT®) platform. The 12-week program consists of five sessions a week (45 minutes each) that include personalized activities planned to stimulate executive functioning, attention, processing speed, and memory.<br>|
| Experimental: Mindfulness & cognitive training group<br>The Mindfulness & cognitive training group receives mindfulness-based stress reduction therapy combined with computer-based cognitive training. | Behavioral: Mindfulness-Based Stress Reduction Program<br>* This intervention follows an adaptation of the scheme and instructions of the official Mindfulness-Based Stress Reduction (MBSR) program designed by Jon Kabat-Zinn. It includes body scanning, sitting meditation, and gentle hatha yoga techniques. An accredited mindfulness instructor leads the 12-week online program, which comprises a presentation session, followed by eight intervention sessions (once a week, lasting 2.5 hours) and an intensive practice session interspersed between sessions six and seven. Apart from the supervised session, the therapist asks participants to carry out some independent practice daily.<br>Behavioral: Computerized Cognitive Training<br>* An accredited neuropsychologist programs and supervises the computerized cognitive training through the Guttmann Neuropersonal Trainer (GNPT®) platform. The 12-week program consists of five sessions a week (45 minutes each) that include personalized activities planned to stimulate executive functioning, attention, processing speed, and memory.<br>|
| Active Comparator: Cognitive training group<br>The Cognitive training group, as an active control group, receives only computer-based cognitive training. | Behavioral: Computerized Cognitive Training<br>* An accredited neuropsychologist programs and supervises the computerized cognitive training through the Guttmann Neuropersonal Trainer (GNPT®) platform. The 12-week program consists of five sessions a week (45 minutes each) that include personalized activities planned to stimulate executive functioning, attention, processing speed, and memory.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in immediate verbal attention after receiving treatment | Forward Digit Span (WAIS III) | 3 months (at baseline, 3 months from baseline) | 
| Change in verbal digit working memory after receiving treatment | Backward Digit Span (WAIS III) | 3 months (at baseline, 3 months from baseline) | 
| Change in verbal memory after receiving treatment | Rey Auditory Learning Test | 3 months (at baseline, 3 months from baseline) | 
| Change in visual memory after receiving treatment | Rey's Complex Figure Test | 3 months (at baseline, 3 months from baseline) | 
| Change in executive function, verbal fluency after receiving treatment | Phonetic Fluency is measured using the Controlled Oral Word Association Test, spanish adaptation, and semantic fluency test using the category Animal | 3 months (at baseline, 3 months from baseline) | 
| Change in executive function, inhibition after receiving treatment | Stroop Test | 3 months (at baseline, 3 months from baseline) | 
| Change in executive function, set-switching task after receiving treatment | Trail Making Test | 3 months (at baseline, 3 months from baseline) | 
| Change in language, naming after receiving treatment | Boston naming Test | 3 months (at baseline, 3 months from baseline) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in psychological distress | Clinical Outcomes in Routine Evaluation (CORE-OM) | 3 months (at baseline, 3 months from baseline) | 
| Changes in depression and anxiety | Depression Anxiety Stress Scale (DASS-21) | 3 months (at baseline, 3 months from baseline) | 
| Changes in wellbeing | Ryff Scales of Psychological Wellbeing. | 3 months (at baseline, 3 months from baseline) | 
| Changes in Mindfulness | Mindful Attention Awareness Scale (MAAS) | 3 months (at baseline, 3 months from baseline) | 
| Changes in White matter integrity | White matter integrity: tractography | 3 months (at baseline, 3 months from baseline) | 
| Changes in Resting-state connectivity | Resting state brain activity using fMRI | 3 months (at baseline, 3 months from baseline) | 
| Changes in brain volumetry | Grey and white matter volume measured by MRI | 3 months (at baseline, 3 months from baseline) | 
| Molecular changes: growth factors (BDNF, SDF1-a, VEGF-A, IGF-1, and NGF), cortisol, protein C reactive, IL-6 and homocysteine levels | Quantification of different biomarkers from blood samples. | 3 months (at baseline, 3 months from baseline) | 
| Changes in Microbiota data | Bacterial composition of stool samples in terms of relative abundance | 3 months (at baseline, 3 months from baseline) | 
| Changes in Sleep | Pittsburgh Sleep Quality Index (PSQI) | 3 months (at baseline, 3 months from baseline) | 
| Changes in Fitness | Senior Fitness Test (SFT) | 3 months (at baseline, 3 months from baseline) | 
| Changes in stroke specific quality of life | Stroke-specific Quality of Life Scale (ECVI-38) | 3 months (at baseline, 3 months from baseline) | 
| Changes in quality of life | World Health Organization Quality of Life (WHOQOL-BREF) | 3 months (at baseline, 3 months from baseline) | 
| Changes in mental fatigue | Fatigue Assessment Scale (FAS) | 3 months (at baseline, 3 months from baseline) | 
| Changes in physical activity: | Spanish version of the reduced Minnesota leisure-time physical and activity questionnaire (VREM) | 3 months (at baseline, 3 months from baseline) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Neuroplasticity, stroke, neuroprotection, physical exercise, cognitive training, mindfulness, neuroimaging, intervention, randomization, blind