Exercise the Mind and Brain. A Multimodal Intervention in Stroke (Mindfit)

• ClinicalTrials.gov Identifier: NCT04759950
• Recruitment Status: Completed
• First Posted: February 18, 2021
• Last Update Posted: March 2, 2022
• Sponsor: University of Barcelona
• Collaborators: Fundació La Marató de TV3; Germans Trias i Pujol Hospital; Institut Guttmann; Jordi Gol i Gurina Foundation; University of Pittsburgh
• Information provided by (Responsible Party): Maria Mataro Serrat, University of Barcelona

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Stroke	Behavioral: Multicomponent Physical Activity Program; Behavioral: Mindfulness-Based Stress Reduction Program; Behavioral: Computerized Cognitive Training	Not Applicable

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:

1. 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.
2. 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.
3. To study the molecular mechanisms by which the different types of interventions influence cognitive, emotional and brain benefits.
4. 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.
5. 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 141 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention 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 (Investigator, Outcomes Assessor)
• Masking Description: The randomization sequence is concealed (blinded) from research personnel, so that the investigators are not aware of whether a particular subject has been randomized to one of the intervention groups or to the active control group.
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: October 28, 2020
• Actual Primary Completion Date: July 30, 2021
• Actual Study Completion Date: January 30, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Physical exercise & cognitive training group; The Physical exercise & cognitive training group receives a multicomponent physical exercise program combined with computer-based cognitive training.	Behavioral: Multicomponent Physical Activity Program; 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).; Behavioral: Computerized Cognitive Training; 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.
Experimental: Mindfulness & cognitive training group; The Mindfulness & cognitive training group receives mindfulness-based stress reduction therapy combined with computer-based cognitive training.	Behavioral: Mindfulness-Based Stress Reduction Program; 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.; Behavioral: Computerized Cognitive Training; 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.
Active Comparator: Cognitive training group; The Cognitive training group, as an active control group, receives only computer-based cognitive training.	Behavioral: Computerized Cognitive Training; 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.

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Spain

Maria Mataro

Barcelona, Spain

Sponsors and Collaborators

University of Barcelona

Fundació La Marató de TV3

Germans Trias i Pujol Hospital

Institut Guttmann

Jordi Gol i Gurina Foundation

University of Pittsburgh

Investigators

• Principal Investigator: Maria Mataro, PhD; University of Barcelona

More Information

• Responsible Party: Maria Mataro Serrat, Professor, University of Barcelona
• ClinicalTrials.gov Identifier: NCT04759950
• Other Study ID Numbers: University of Barcelona; 201717.30.31.32 ( Other Grant/Funding Number: La Marato de TV3 )
• First Posted: February 18, 2021
• Last Update Posted: March 2, 2022
• Last Verified: March 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Maria Mataro Serrat, University of Barcelona:

Neuroplasticity; stroke; neuroprotection; physical exercise; cognitive training; mindfulness; neuroimaging; intervention; randomization; blind

Additional relevant MeSH terms:

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases