Heart-Brain Retraining for Stroke Rehabilitation

• Sponsor: The Cleveland Clinic (Other)
• Overall Status: Completed
• CT.gov ID: NCT02076776
• Collaborator: (none)
• Enrollment: 21
• Location: 1
• Arms: 3
• Duration (Months): 27
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

The purpose of this study is to gain a better understanding of how different types of exercise can help people after a stroke. The investigators want to study if different types of exercise will improve the use of arm and hand function after a stroke.

Condition or Disease	Intervention/Treatment	Phase
Stroke	Behavioral: Repetitive Task Practice (RTP); Behavioral: Voluntary cycling + RTP; Behavioral: Assisted cycling + RTP	N/A

Detailed Description

Stroke is the leading cause of disability in the United States with approximately 795,000 new or recurrent strokes per year. An estimated two thirds of patients post-stroke cannot incorporate the affected upper extremity (UE) into their activities of daily living. In addition, stroke survivors experience a 60% decrease in cardiovascular capacity, which contributed to disability and diminished quality of life. Developing rehabilitation techniques to optimize motor recovery while improving cardiovascular endurance would benefit the stroke population.

Animal studies using a forced exercise (FE) paradigm, in which the rodent is exercised on a motorized treadmill at a rate greater than its voluntary rate, indicate an endogenous increase in neurotrophic factors such as brain-derived neurotrophic factor (BDNF) and glial-derived neurotrophic factor (GDNF). These neurotrophic factors are thought to underlie neuroplasticity and motor learning. It is hypothesized that patients with stroke, due to decreased motor cortical output, cannot sustain high rates of voluntary exercise necessary to trigger the endogenous release of neurotrophic factors; therefore, forced-exercise is necessary to augment their voluntary efforts and will be superior to voluntary exercise in facilitating motor recovery. When coupled with repetitive task practice (RTP) of the UE, an effective form of UE rehabilitation, FE will prime the brain for neuroplasticity. We have developed a safe and effective method of delivering forced-exercise to Parkinson's disease (PD) patients (NIH R21HD056316). Clinical and imaging data with PD patients indicate forced-exercise, but not voluntary exercise, triggers a neurophysiologic response in the central nervous system resulting in global improvements in motor and non-motor functioning and increased cortical and subcortical activation. The aim of this project is to conduct a preliminary trial to compare the effects of forced to voluntary exercise when coupled with RTP in promoting the recovery of motor function in patients with stroke.

Study Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Heart-Brain Retraining: Forced Aerobic Exercise for Stroke Rehabilitation
• Study Start Date: Aug 1, 2012
• Actual Primary Completion Date: Nov 1, 2014
• Actual Study Completion Date: Nov 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Repetitive Task Practice (RTP) This group focuses on RTP.	Behavioral: Repetitive Task Practice (RTP); This group will preform arm and hand therapy.
Experimental: Voluntary cycling + RTP This group involves one biking session and one RTP session three times per week for eight weeks.	Behavioral: Voluntary cycling + RTP; This group will preform arm and hand therapy and cycle on a bike.
Experimental: Assisted cycling + RTP This group involves one biking session and one RTP session three times per week for eight weeks.	Behavioral: Assisted cycling + RTP; This group will preform arm and hand therapy and cycle on a bike.

Outcome Measures

Primary Outcome Measures

1. Wolf Motor Function Test (WMFT) [Baseline, End of Treatment (8 weeks); End of Treatment + 4 week (12 weeks)]

   This consists of 2 strength tasks and 15 timed tasks of both the affected UE and the unaffected UE. Total Functional Ability Score is reported, scores range from 0-75, with higher scores indicating a better outcome.

Secondary Outcome Measures

1. The Fugl-Meyer Assessment (FMA) [Baseline, End of Treatment (8 weeks); End of Treatment + 4 week (12 weeks)]

   This is a 33 item assessment of post-stroke UE impairment. Total score is reported, scores range from 0-66, with higher scores indicating a better outcome.

Other Outcome Measures

1. The Stroke Impact Scale (SIS) [Baseline, End of Treatment (8 weeks); End of Treatment + 4 week (12 weeks)]

   This is a self-reported questionnaire evaluating quality of life. Normalized Hand Function is reported, scores range from 0-100, with higher scores indicating a better outcome.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Able to provide informed consent

• Within 6-12 months of diagnosis of single ischemic or hemorrhagic stroke, confirmed with neuroimaging

• Fugl-Meyer Motor Score 19-55 in involved upper extremity

• Approval from patient's primary care physician

• Age between 18 and 85 years

Exclusion Criteria:

• Hospitalization for myocardial infarction, congestive heart failure, or heart surgery (CABG or valve replacement) within 3 months of study enrollment

• Serious cardiac arrhythmia

• Hypertrophic cardiomyopathy

• Severe aortic stenosis

• Cardiac pacemaker

• Pulmonary embolus

• Other medical or musculoskeletal contraindication to exercise

• Significant cognitive impairment (unable to follow 1-2 step commands) or major psychiatric disorder (major depression, generalized anxiety) that will cause difficulty in study participation

• Anti-spasticity injection (botox) in upper extremity within 3 months of study enrollment

• Pregnancy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cleveland Clinic	Cleveland	Ohio	United States	44195

Sponsors and Collaborators

• The Cleveland Clinic

Investigators

• Principal Investigator: Jay Alberts, PhD, The Cleveland Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jay Alberts, Principle Investigator, The Cleveland Clinic
• ClinicalTrials.gov Identifier: NCT02076776
• Other Study ID Numbers: R03HD073566
• First Posted: Mar 4, 2014
• Last Update Posted: Aug 31, 2018
• Last Verified: Aug 1, 2018

• Keywords provided by Jay Alberts, Principle Investigator, The Cleveland Clinic: Stroke; Exercise; Rehabilitation; Neuroplasticity; Task Practice
• Additional relevant MeSH terms: Stroke

Study Results

Participant Flow

Pre-assignment Detail	One participant consented to the study, but had abnormal stress test results. This participant declined follow-up care and withdrew from the study before completing the baseline and randomization process.

Arm/Group Title	Repetitive Task Practice (RTP)	Voluntary Cycling + RTP	Assisted Cycling + RTP
Arm/Group Description	This group focuses on RTP. Repetitive Task Practice (RTP): This group will preform arm and hand therapy.	This group involves one biking session and one RTP session three times per week for eight weeks. Voluntary cycling + RTP: This group will preform arm and hand therapy and cycle on a bike.	This group involves one biking session and one RTP session three times per week for eight weeks. Assisted cycling + RTP: This group will preform arm and hand therapy and cycle on a bike.
Period Title: Overall Study
STARTED	6	8	6
COMPLETED	5	6	6
NOT COMPLETED	1	2	0

Baseline Characteristics

Arm/Group Title	Repetitive Task Practice (RTP)	Voluntary Cycling + RTP	Assisted Cycling + RTP	Total
Arm/Group Description	This group focuses on RTP. Repetitive Task Practice (RTP): This group will preform arm and hand therapy.	This group involves one biking session and one RTP session three times per week for eight weeks. Voluntary cycling + RTP: This group will preform arm and hand therapy and cycle on a bike.	This group involves one biking session and one RTP session three times per week for eight weeks. Assisted cycling + RTP: This group will preform arm and hand therapy and cycle on a bike.	Total of all reporting groups
Overall Participants	6	8	6	20
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	5 83.3%	5 62.5%	6 100%	16 80%
>=65 years	1 16.7%	3 37.5%	0 0%	4 20%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.67 (7.45)	59.38 (15.57)	44.83 (11.72)	55.70 (13.94)
Sex: Female, Male (Count of Participants)
Female	0 0%	3 37.5%	1 16.7%	4 20%
Male	6 100%	5 62.5%	5 83.3%	16 80%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%
Not Hispanic or Latino	6 100%	8 100%	6 100%	20 100%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	1 16.7%	1 5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	2 33.3%	2 25%	2 33.3%	6 30%
White	4 66.7%	6 75%	3 50%	13 65%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	6 100%	8 100%	6 100%	20 100%
Wolf Motor Function Test (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	45.17 (17.38)	49.75 (20.25)	59.83 (9.06)	51.40 (16.97)
Fugl-Meyer Assessment (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	26.83 (7.83)	34.75 (13.58)	36.17 (7.41)	32.80 (10.72)
Stroke Impact Scale (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	31.67 (35.73)	34.38 (28.72)	50.83 (32.00)	38.50 (31.29)

Outcome Measures

1. Primary Outcome

Title	Wolf Motor Function Test (WMFT)
Description	This consists of 2 strength tasks and 15 timed tasks of both the affected UE and the unaffected UE. Total Functional Ability Score is reported, scores range from 0-75, with higher scores indicating a better outcome.
Time Frame	Baseline, End of Treatment (8 weeks); End of Treatment + 4 week (12 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Repetitive Task Practice (RTP)	Voluntary Cycling + RTP	Assisted Cycling + RTP
Arm/Group Description	This group focuses on RTP. Repetitive Task Practice (RTP): This group will preform arm and hand therapy.	This group involves one biking session and one RTP session three times per week for eight weeks. Voluntary cycling + RTP: This group will preform arm and hand therapy and cycle on a bike.	This group involves one biking session and one RTP session three times per week for eight weeks. Assisted cycling + RTP: This group will preform arm and hand therapy and cycle on a bike.
Measure Participants	5	6	6
Baseline	45.17 (17.38)	49.75 (20.25)	59.83 (9.06)
EOT	49.80 (18.94)	48.83 (18.10)	68.67 (6.31)
EOT+4	50.80 (21.35)	50.33 (19.35)	69.50 (5.61)

2. Secondary Outcome

Title	The Fugl-Meyer Assessment (FMA)
Description	This is a 33 item assessment of post-stroke UE impairment. Total score is reported, scores range from 0-66, with higher scores indicating a better outcome.
Time Frame	Baseline, End of Treatment (8 weeks); End of Treatment + 4 week (12 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Repetitive Task Practice (RTP)	Voluntary Cycling + RTP	Assisted Cycling + RTP
Arm/Group Description	This group focuses on RTP. Repetitive Task Practice (RTP): This group will preform arm and hand therapy.	This group involves one biking session and one RTP session three times per week for eight weeks. Voluntary cycling + RTP: This group will preform arm and hand therapy and cycle on a bike.	This group involves one biking session and one RTP session three times per week for eight weeks. Assisted cycling + RTP: This group will preform arm and hand therapy and cycle on a bike.
Measure Participants	5	6	6
Baseline	26.83 (7.83)	34.75 (13.58)	36.17 (7.41)
EOT	29.80 (11.97)	35.33 (14.65)	48.50 (6.75)
EOT+4	33.40 (15.04)	37.00 (17.56)	51.17 (3.06)

3. Other Pre-specified Outcome

Title	The Stroke Impact Scale (SIS)
Description	This is a self-reported questionnaire evaluating quality of life. Normalized Hand Function is reported, scores range from 0-100, with higher scores indicating a better outcome.
Time Frame	Baseline, End of Treatment (8 weeks); End of Treatment + 4 week (12 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Repetitive Task Practice (RTP)	Voluntary Cycling + RTP	Assisted Cycling + RTP
Arm/Group Description	This group focuses on RTP. Repetitive Task Practice (RTP): This group will preform arm and hand therapy.	This group involves one biking session and one RTP session three times per week for eight weeks. Voluntary cycling + RTP: This group will preform arm and hand therapy and cycle on a bike.	This group involves one biking session and one RTP session three times per week for eight weeks. Assisted cycling + RTP: This group will preform arm and hand therapy and cycle on a bike.
Measure Participants	5	6	6
Baseline	31.67 (35.73)	34.38 (28.72)	50.83 (32.00)
EOT	35.00 (26.93)	45.00 (41.95)	68.33 (15.38)
EOT+4	34.00 (22.75)	51.67 (37.24)	66.67 (22.73)

Adverse Events

Arm/Group Title	Repetitive Task Practice (RTP)		Voluntary Cycling + RTP		Assisted Cycling + RTP
Arm/Group Description	This group focuses on RTP. Repetitive Task Practice (RTP): This group will preform arm and hand therapy.		This group involves one biking session and one RTP session three times per week for eight weeks. Voluntary cycling + RTP: This group will preform arm and hand therapy and cycle on a bike.		This group involves one biking session and one RTP session three times per week for eight weeks. Assisted cycling + RTP: This group will preform arm and hand therapy and cycle on a bike.
All Cause Mortality
	Repetitive Task Practice (RTP)		Voluntary Cycling + RTP		Assisted Cycling + RTP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		1/8 (12.5%)		0/6 (0%)
Serious Adverse Events
	Repetitive Task Practice (RTP)		Voluntary Cycling + RTP		Assisted Cycling + RTP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		1/8 (12.5%)		0/6 (0%)
General disorders
Recurrent stroke	0/6 (0%)	0	1/8 (12.5%)	1	0/6 (0%)	0
Other (Not Including Serious) Adverse Events
	Repetitive Task Practice (RTP)		Voluntary Cycling + RTP		Assisted Cycling + RTP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/8 (0%)		0/6 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.