Clinical trial NCT04259424: Exercise-primed Upper Extremity Motor Practice in Chronic Stroke
Official title: Priming Upper Extremity Motor Practice With Aerobic Exercise: A Feasibility and Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Stroke
Keywords: Rehabilitation
Upper Extremity
Aerobic Exercise
Motor Function
Lead sponsor: Medical University of South Carolina
Sponsor class: OTHER
First posted: 2020-02-06
Enrollment: 10
Sex: ALL
Minimum age (years): 21
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: All subjects enrolled will receive the same treatment. Upper extremity motor function outcome measures will be assessed.
Primary purpose: TREATMENT

Brief summary: The purpose of this project is to establish initial feasibility and tolerability of a combined aerobic exercise (AEx) and upper extremity motor practice intervention on upper extremity (UE) function in chronic stroke survivors. This novel intervention pairs AEx with a virtual reality-based upper extremity rehabilitation game, Duck Duck Punch (DDP). AEx has been shown to improve overall brain function and promote a healthy brain environment; thus it may serve as an effective 'primer' and enhance the effects of DDP. Movement-based priming for rehabilitation involves performing movement or exercise before, or simultaneous to, an intervention with the goal of improving the effectiveness of the intervention. AEx combined with UE rehabilitation can improve UE function and self-reported health status in chronic stroke survivors. However, gaps remain regarding the clinical applicability of an AEx priming session and the mechanisms contributing to changes in UE functions in response to AEx-primed UE rehabilitation. Therefore, the aim of this project is to: 1) demonstrate the feasibility of pairing AEx + DDP in stroke survivors; 2) quantify the magnitude of the effect of the AEx + DDP intervention on UE function; 3) examine relationship of biomarkers of the nervous system and response to AEx + DDP.

Detailed description: With a surviving cohort of nearly 7 million individuals, stroke is the leading cause of long-term disability in the United States. Of the \~795,000 new strokes occurring annually, approximately 2/3rds of survivors will have some degree of long term disability. The prevalence of post-stroke disability coupled with the fact that more people are surviving stroke reflects an increasing need to develop effective rehabilitation strategies aimed at reducing disability and improving quality of life for the millions of stroke survivors, their families and caregivers.

The overwhelming majority of stroke survivors, \>75%, exhibit upper extremity (UE) hemiparesis, and only 15% will recover fully. Furthermore, residual UE impairment is closely linked to long-term disability and reduced quality of life. Current meta-analytic evidence supports virtual reality stroke rehabilitation interventions for improving UE function suggesting that this is a promising area for further therapeutic development.

Duck Duck Punch (DDP) is an interactive computer game deliberately designed to enhance UE movement quality via individualized progressive movement practice along with an array of performance metrics allowing for within-session feedback on movement performance. Although response to UE virtual reality rehabilitation interventions, such as DDP, involves a multitude of factors, neuroplastic changes are a primary mechanism underlying functional recovery. Thus, pairing DDP with a priming intervention to facilitate a 'neuroplastic-friendly' environment may make the CNS more amenable, and enhance response to DDP rehabilitation and ultimately improve outcomes.

Aerobic exercise (AEx) training has positive benefits on overall brain function including enhanced global cognition, executive function, and processing speed and attention in healthy, older adults. Additionally, a single session of AEx acutely improves motor memory and learning in younger, healthy adults. Although AEx has been used to improve cardiovascular function following stroke, its neurofacilitatory effects in stroke have yet to be tested empirically. Candidate mechanisms through which AEx enhances brain function and motor learning include changes in circulating brain-derived neurotrophic factor (BDNF) and corticomotor excitability. BDNF is believed to play an integral role in several neuroplastic processes and promotes the strengthening of synaptic connections, i.e. long-term potentiation (LTP) and current research indicates that AEx can acutely and chronically increase circulating BDNF. Corticomotor excitability (CME) is often used as an indicator of LTP-like neuroplasticity and may underlie improvements in motor memory and learning. Similarly to BDNF, AEx can acutely enhance corticomotor excitability in control and chronic stroke subjects. Facilitating central nervous system function provides rationale to determine the role of AEx in 'prime' the brain for a subsequent intervention to maximize neuroplastic potential.

Movement-based priming for neurorehabilitation involves performing movement or exercise before, or concurrent to, a therapeutic intervention with the goal of improving the efficacy of the therapeutic intervention. Emerging evidence supports AEx as a potential priming tool for UE stroke rehabilitation. AEx combined with UE task training can improve UE function and self-reported health status in chronic stroke survivors. Despite the promising results, there are gaps in the literature involving: 1) the clinical applicability of an AEx priming session; and 2) mechanisms contributing to changes in UE functions in response to AEx-primed UE rehabilitation. Addressing these gaps will be necessary to develop an AEx primer that is potent and time efficient, with respect to current clinical models. Therefore, the purpose of this pilot proposal will be to establish initial feasibility and tolerability benchmarks via the following aims:

1. Demonstrate the feasibility of pairing AEx + DDP in stroke survivors with UE hemiparesis
2. Quantify the magnitude of the effect of the AEx + DDP intervention on UE impairment and function
3. Examine the relationship of biomarkers of neuroplasticity (BDNF and corticomotor excitability) and response to AEx + DDP

To accomplish these aims, chronic stroke survivors with moderate UE hemiparesis will undergo 18 sessions of AEx + DDP training. Each week, for six weeks, subjects will undergo three sessions of AEx + DDP. During each session subjects will complete 15 minutes of aerobic exercise followed by 200 repetitions of DDP. Assessment of UE function and biomarkers of neuroplasticity will be assessed before and after the AEx + DDP intervention.

Eligibility criteria: Inclusion Criteria:

* experienced unilateral stroke at least 6 months, but no more than 120 months prior
* voluntary shoulder flexion of the affected arm ≥20° with simultaneous elbow extension ≥10°
* moderate arm movement impairment (UE Fugl-Meyer Assessment \> 21 but \< 52 points
* passive range of motion in paretic shoulder, elbow, wrist, thumb and fingers within 20 degrees of normal
* 21-90 years of age
* ability to communicate as per the therapists' judgement at baseline testing
* ability to complete and pass an exercise tolerance test

Exclusion Criteria:

* lesion in brainstem/cerebellum as these may interfere with visual-perceptual/cognitive skills needed for motor re-learning
* presence of other neurological disease that may impair motor learning skills
* orthopedic condition or impaired corrected vision that alters reaching ability (e.g., prior rotator cuff tear without full recovery)
* paretic arm pain that interferes with reaching
* unable to understand or follow 3-step directions
* severe cognitive impairment (Montreal Cognitive Assessment score \<22)
* severe aphasia
* inability to read English
* history of congestive heart failure, unstable cardiac arrhythmias, hypertrophic cardiomyopathy, severe aortic stenosis, angina or dyspnea at rest or during ADL's
* Severe hypertension with systolic \>200 mmHg and diastolic \>110 mmHg at rest
* history of, or current, depression and for brain stimulation procedures only
* women of child-bearing potential
* electronic or metallic implants
* history of seizures

Primary outcomes:
measure: Change in Upper Extremity Impairment as Assessed by the Fugl-Meyer Assessment - Upper Extremity
timeFrame: Pre and post intervention, approximately 6 weeks
Secondary outcomes:
measure: Change in Upper Extremity as Assessed by the Wolf Motor Function Test
timeFrame: Pre and post intervention, approximately 6 weeks
measure: Change in Physical Function and Health-related Quality of Life as Assessed by Stroke Impact Scale
timeFrame: Pre and post intervention, approximately 6 weeks
Other outcomes:
measure: Change in Neuroplastic Potential as Assessed by Paired Associative Stimulation
timeFrame: Pre and post intervention, approximately 6 weeks
measure: Assessment of Peripheral Brain-derived Neurotrophic Factor
timeFrame: Pre and post aerobic exercise on intervention sessions 1, 9, and 18. Each aerobic exercise session will be 15 minutes
Locations:
city: Charleston
country: United States
facility: Stroke Recovery Research Center
state: South Carolina
Study officials:
affiliation: Medical University of South Carolina
name: Chris Gregory, PhD, PT
role: STUDY_DIRECTOR
References: