Recovery Improved in Covert Stroke With Exercise (RISE-2)

Achieving Brain Benefits in Covert Stroke Through Aerobic Exercise

Silent ischemic, also known as "covert stroke vascular disease" (CSVD), contributes to neurological deficits that are caused by damage to small blood vessels in the brain. CSVD occurs six to ten times more often that an acute stroke. It is misleading to think, however, that CSVD is an inevitable part of "getting old" because people with CSVD are at high risk of developing an acute stroke or dementia. In fact, people with more CSVD lesion volume are more likely to develop day to day problems in planning, decision-making and speed of thinking. Unfortunately, there are no proven therapies designed to address CSVD. We propose to test whether aerobic exercise is an intervention that can combat CSVD because the disease is fundamentally a blood flow problem that may be improved by aerobic exercise. We will recruit CSVD adults with moderate to severe lesion burden and use magnetic resonance imaging (MRI) to study the brain in terms of structure, perfusion and function. Participants will be randomly assigned to either our established aerobic exercise program or a control stretching program. Both groups will take part in lab exercise sessions, which are designed to monitor progress and assess adherence to the program. The duration and intensity of their exercise will increase as participants progress. We will use activity log books, phone calls and extra "booster" exercise sessions, as needed, to maximize retention and adherence. We aim to show that aerobic exercise increases cerebral blood flow (CBF) in frontal-subcortical grey matter, supports regional tissue growth, and improves cognitive function in CSVD adults with substantial risk of acute stroke and dementia. A positive outcome of this research will provide strong support for additional clinical trials aimed at sustaining cognition and maintaining independent living.

Study Overview

• Status: Completed
• Conditions: Cerebral Small Vessel Diseases
• Intervention / Treatment: Behavioral: Exercise Program; Behavioral: Stretching Program

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Covert stroke: white matter hyperintensities of presumed vascular origin
• Ability to walk for 10 minutes without assistance from another person
• Fluent in English
• Ability to consent

Exclusion Criteria:

• Highly fit individuals exercising ≥ 150 minutes per week
• Dementia
• Multiple Sclerosis
• Disabling stroke (ischemic or hemorrhagic)
• Major concurrent illness (e.g. chronic obstructive lung disorder, current or metastatic cancer, chronic kidney disease)
• Major psychiatric illness (e.g. bipolar, schizophrenia, major depression)
• Contraindications to MRI scanning (e.g. claustrophobia, implants, prostheses, metallic fragments)
• Contraindications to exercise (participants must have medical clearance to exercise from their attending physician)
• Recent change in health status (e.g. hospitalization within past month)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Exercise; This group will perform the 'Exercise Program' for months 0 to 6, and will be unsupervised for months 7 to 12.	Behavioral: Exercise Program; The 'Exercise Program' will prescribe specific aerobic exercise to the participants. Supervised group exercise will be performed once per week (60 minutes) and self-directed exercise will be encouraged 4 days per week and monitored by an activity journal. The initial walking prescription will be set at ~1.6 km and an intensity equivalent to the anaerobic threshold and/or 60% of peak oxygen uptake. Progressions will be made every 2 weeks, increasing distance to a maximum of 6.4 km and then increasing to a max intensity of 80% of peak oxygen uptake and/or max duration of 60 minutes. Heart rate and perceived exertion will be monitored. The program will last 6 months.
Active Comparator: Stretching; This group will perform the 'Stretching Program' for months 0 to 6, and the 'Exercise Program' for months 7 to 12.	Behavioral: Exercise Program; The 'Exercise Program' will prescribe specific aerobic exercise to the participants. Supervised group exercise will be performed once per week (60 minutes) and self-directed exercise will be encouraged 4 days per week and monitored by an activity journal. The initial walking prescription will be set at ~1.6 km and an intensity equivalent to the anaerobic threshold and/or 60% of peak oxygen uptake. Progressions will be made every 2 weeks, increasing distance to a maximum of 6.4 km and then increasing to a max intensity of 80% of peak oxygen uptake and/or max duration of 60 minutes. Heart rate and perceived exertion will be monitored. The program will last 6 months.; Behavioral: Stretching Program; The 'Stretching Program' will teach stretching for the upper and lower limbs, and the trunk, as well as breathing exercises for relaxation. Supervised group activities will be performed once per week (45 minutes) and self-directed stretching will be encouraged 4 days per week and monitored by an activity journal. The intensity of stretching and number of stretches will be progressed every 2 weeks. Heart rate and perceived exertion will be monitored. The program will last 6 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in cerebral blood flow from baseline to 6 months	Pseudo-continuous arterial spin labeling MRI	6 months
Change in brain structure from baseline to 6 months	Cortical and subcortical grey matter density using structural MRI	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in brain activity related to attention and executive control tasks from baseline to 6 months	Blood oxygenation level dependent MRI	6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in white matter integrity from baseline to 6 months	Diffusion tensor imaging (DTI) MRI	6 months
Change in aerobic fitness from baseline to 6 months	Peak oxygen uptake	6 months
Change in aerobic fitness from 6 to 12 months	Peak oxygen uptake	12 months
Change in autonomic function from baseline to 6 months	Heart rate variability	6 months
Change in autonomic function from 6 to 12 months	Heart rate variability	12 months
Change in arterial stiffness from baseline to 6 months	Carotid-femoral pulse wave velocity	6 months
Change in arterial stiffness from 6 to 12 months	Carotid-femoral pulse wave velocity	12 months
Change in executive function from baseline to 6 months	Trail Making Test	6 months
Change in executive function from 6 to 12 months	Trail Making Test	12 months
Change in balance from baseline to 6 months	Spatial-temporal synchronization of center of pressure	6 months
Change in balance from 6 to 12 months	Spatial-temporal synchronization of center of pressure	12 months
Change in dual task gait from baseline to 6 months	Comparison of normal gait to gait with verbal math challenge	6 months
Change in dual task gait from 6 to 12 months	Comparison of normal gait to gait with verbal math challenge	12 months
Change in grip strength from baseline to 6 months	Maximum grip strength with dynamometer	6 months
Change in grip strength from 6 to 12 months	Maximum grip strength with dynamometer	12 months

Collaborators and Investigators

• Sponsor: Sunnybrook Health Sciences Centre
• Collaborators: Toronto Rehabilitation Institute
• Investigators: Principal Investigator: Bradley MacIntosh, PhD, Sunnybrook Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2015
• Primary Completion (Actual): March 7, 2018
• Study Completion (Actual): September 12, 2018

Study Registration Dates

• First Submitted: February 19, 2014
• First Submitted That Met QC Criteria: February 20, 2014
• First Posted (Estimate): February 21, 2014

Study Record Updates

• Last Update Posted (Actual): September 18, 2018
• Last Update Submitted That Met QC Criteria: September 17, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: aerobic exercise; executive function; cerebral blood flow; covert stroke; grey matter; attention
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cerebral Small Vessel Diseases
• Other Study ID Numbers: RISE2-2014-312185

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No