Motor function may be enhanced if aerobic exercise is paired with motor training. One potential mechanism is that aerobic exercise increases levels of brain-derived neurotrophic factor (BDNF), which is important in neuroplasticity and involved in motor learning and motor memory consolidation. This study will examine the feasibility of a parallel-group assessor-blinded randomised controlled trial investigating whether task-specific training preceded by aerobic exercise improves upper limb function more than task-specific training alone, and determine the effect size of changes in primary outcome measures. People with upper limb motor dysfunction after stroke will be allocated to either task-specific training or aerobic exercise and consecutive task-specific training. Both groups will perform 60 hours of task-specific training over 10 weeks, comprised of 3 × 1 hour sessions per week with a therapist and 3 × 1 hours of home-based self-practice per week. The combined intervention group will also perform 30 minutes of aerobic exercise (70–85%HRmax) immediately prior to the 1 hour of task-specific training with the therapist. Recruitment, adherence, retention, participant acceptability, and adverse events will be recorded. Clinical outcome measures will be performed pre-randomisation at baseline, at completion of the training program, and at 1 and 6 months follow-up. Primary clinical outcome measures will be the Action Research Arm Test (ARAT) and the Wolf Motor Function Test (WMFT). If aerobic exercise prior to task-specific training is acceptable, and a future phase 3 randomised controlled trial seems feasible, it should be pursued to determine the efficacy of this combined intervention for people after stroke.
Currently 440,000 persons after stroke live in community settings in Australia . Many with stroke experience chronic disability and although two-thirds receive care each day , the majority still have unmet needs . Upper limb dysfunction is a persistent and disabling problem present in 69% of persons after stroke in Australia . Upper limb dysfunction is a major contributor to poor well-being and quality-of-life ; ;  ; . Unsurprisingly, advancing treatments for upper limb recovery is a top ten research priority for persons after stroke and their carers .
In Australia, 87% of persons with stroke-attributable upper limb impairments receive task-specific training . Task-specific training is a progressive training strategy that utilises practice of goal-directed, real-world, context-specific tasks that are intrinsically and/or extrinsically meaningful to the person, to enable them to undertake activities of daily living  and may improve upper limb motor function after stroke ;  ; .
Improvements in motor function coincide with structural and functional reorganisation of the brain ; ;  ; . The brain’s ability to undergo these changes is denoted as neuroplasticity. Capitalisation and enhancement of neuroplasticity in peri-infarct and non-primary motor regions may promote recovery via an increased response to motor training and other neurorehabilitative interventions ;  ; .
Many studies show that aerobic exercise (prolonged, rhythmical activity using large muscle groups to increase heart rate) enhances neuroplasticity , grey matter volume, white matter integrity ;  ;  and brain activation ;  ; . Furthermore increasing evidence indicates that lower limb aerobic exercise increases upper limb motor function. A single bout of aerobic cycling exercise can improve long-term retention of a motor skill in healthy individuals , regardless of whether performed immediately before or after motor training .
Aerobic exercise increases BDNF . Improvements in motor skill learning and memory induced by aerobic exercise have been associated with increased peripheral blood concentrations of BDNF . BDNF is involved with neurogenesis  and neuroprotection  in the human brain , thereby playing an important role in stroke recovery, including facilitating functional upper limb motor rehabilitation .
In chronic stroke, an 8-week programme of lower extremity endurance cycling enhanced upper extremity fine motor control . Also, a single bout of aerobic treadmill exercise improved grasp function of the hemiparetic hand . As aerobic exercise alone can enhance motor function after stroke, motor learning in stroke rehabilitation may be facilitated if aerobic exercise is paired with motor training  ; .
1.2. Aims and objectives
The aims of this study are to 1) assess the feasibility of conducting a randomised controlled trial to compare the effects of task-specific training preceded by aerobic exercise to task-specific training alone on upper limb motor function after stroke; and 2) calculate the effect size of changes in primary clinical outcome measures to evaluate proof-of-concept and inform calculation of sample size for a future phase III trial. This includes investigating potential neural correlates of exercise-induced motor function changes using peripheral blood serum BDNF measurement and multi-modal MRI.
2.1. Study design
This is a parallel-group assessor-blinded randomised controlled pilot study (Fig. 1). One group will undertake task-specific training alone and the other group will undertake 30 minutes of aerobic cycling exercise prior to their task-specific training. The interventions will be delivered by a therapist 3 days per week for 10 weeks. Both groups will be provided with an individually-prescribed task-specific training programme to practice at home for 60 minutes, 3 times per week. Assessments will be conducted at baseline, within 1 week from the end of intervention, and 1 and 6 months following the end of the intervention period. Ethics approval has been obtained from the Hunter New England Human Research Ethics Committee (14/12/10/4.07) and registered with the University of Newcastle Human Research Ethics Committee (H-2015-0105). The study is registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12616000848404).