Clinical trial NCT04742686: Aerobic Exercise Training in Acute Ischaemic Stroke
Official title: Aerobic Exercise Training in Acute Ischaemic Stroke: A Single-centre, Single-blinded, Randomised, Controlled Feasibility Study of an Aerobic Exercise Training Intervention Versus Standard Care Conducted in the Acute Phase of Stroke.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Ischemic Stroke
Acute Stroke
Cerebrovascular Accident
Keywords: Aerobic exercise
Power-assisted exercise
Feasibility
Acute stroke
Ischaemic stroke
Lead sponsor: Sheffield Hallam University
Sponsor class: OTHER
Collaborators: name: Sheffield Teaching Hospitals NHS Foundation Trust
First posted: 2021-02-08
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: Stroke is a leading cause of adult disability in the UK. There are few treatment options that improve long-term disability outcomes after stroke. Animal studies indicate that aerobic exercise training can improve brain repair and reduce disability after stroke. However, in clinical practice it is difficult for stroke survivors to undertake aerobic exercise due to lower-limb disability and a lack of accessible exercise equipment. This study will assess the feasibility of implementing a 5-day aerobic exercise training intervention, beginning in the acute phase of stroke (1-7 days post-stroke), using a power-assisted exercise bike. Feasibility outcome measures: recruitment rate (30 participants recruited within 18 months), completeness of data (\>80% of planned measurements recorded) and the safety (\<10 adverse events related to the intervention) and acceptability (\>3/5 comfort scale) of the intervention. We will also investigate the acute effects of aerobic exercise on cerebral blood flow velocity using transcranial Doppler ultrasound, and brain-derived neurotrophic factor (serum and plasma).

Detailed description: Introduction

Pre-clinical studies indicate that aerobic exercise training can enhance brain repair and reduce disability when initiated early (1-7 days) after stroke. However, in the real-world clinical setting, most acute stroke patients have a lower-limb disability which makes it difficult to engage in aerobic exercise. Power-assisted exercise bikes can detect lower-limb motor deficits and compensate with motorised assistance. The primary aim of this study is to assess the feasibility of implementing a 5-day power-assisted aerobic exercise training programme, initiated in the acute phase of ischaemic stroke (1-7 days post-stroke). Key feasibility outcomes related to the intervention include safety (\<10 adverse events related to the intervention) and acceptability (\>3/5 comfort scale). The secondary aim is to assess the feasibility of conducting a randomised controlled trial (RCT), with a focus on study procedures including recruitment (30 participants recruited within 18 months) and completeness of data (≥80% of planned measurements recorded), and identification of a suitable primary outcome measure for a large-scale RCT.

Recruitment

People with acute ischaemic stroke admitted to the Royal Hallamshire Hospital (Sheffield, England) will be recruited to this study. After eligible individuals provide informed consent, a web-based permuted block randomisation procedure will be used to allocate participants into one of two study arms: 1) usual care; or 2) aerobic exercise training plus usual care. Participants will be stratified using the National Institutes of Health Stroke Scale (NIHSS): mild to moderate (0-15) and moderate to severe (\>15) measured after reperfusion therapy or at a similar timepoint if not eligible for reperfusion therapy. Accounting for a predicted attrition rate of 20%, the target sample size is 30 participants.

Intervention

A bedside power-assisted exercise bike will be used to enable patients to undertake aerobic exercise whilst remaining in their bed, even if they have a lower-limb disability. The aerobic exercise programme will consist of five exercise sessions, each including a graduated warm-up, a conditioning phase, and a graduated cooldown. The conditioning phase will be an interval training format, with five-minute low- to moderate-intensity intervals interspersed with one-minute rest periods. The number of five-minute conditioning bouts will increase by one bout per session. The first session will contain two bouts (total = 10 mins), and the fifth session will contain six bouts (total = 30 mins). The rationale for this progressive design was developed with input from researchers, healthcare practitioners and people affected by stroke. Briefly, it was considered that starting with 30 minutes of aerobic exercise in the first session may be too difficult for some patients due to fatigue, whereas a gradual progression in exercise duration would be more tolerable. In addition, the interval training design was chosen to reduce exercise-induced fatigue, and thereby increase the total duration of aerobic exercise completed per session. Participants will cycle at a steady self-selected cadence, and exercise intensity will be guided by the Borg rating of perceived exertion (RPE) scale. During the conditioning intervals, participants will be asked to the cycle at an intensity equivalent to 'somewhat hard' (RPE:13/20). Heart rate, peripheral oxygen saturation, brachial blood pressure, and symptoms will be monitored throughout each exercise session. In the fourth or fifth exercise session, exercise-induced changes in respiratory gases, cerebral blood flow velocity and blood-borne brain-derived neurotrophic factor will be assessed. Established clinical exercise physiology guidelines will be followed with regards to exercise contraindications and termination criteria.

Usual care

Participants randomised to the control group will receive usual care according to guidance from the National Institute for Health and Care Excellence and the Royal College of Physicians. Briefly, it is recommended that patients undertake at least 45 minutes of each appropriate therapy per day (physiotherapy, occupational therapy and or speech and language therapy) for five days per week. Patients should be mobilised (out-of-bed sitting, standing or walking) within the first 48 hours of stroke onset, or if physically capable, as soon as possible post-stroke.

Interviews

7-14 days after enrolling in the study, a convenience sample of participants (n=8 per study arm) will be interviewed to gain insight into participants' experiences participating in the study activities (e.g. intervention and or assessments). Repeat interviews will be conducted with the same individuals three months later with a focus on their post-hospital rehabilitation experiences. In addition, a small convenience sample (n=3-5) of clinical staff members will be interviewed to understand their opinions about the intervention and overall study procedures.

Eligibility criteria: Inclusion Criteria:

* Adult (age \>18 years) patients diagnosed with acute ischaemic stroke 1-7 days previously.
* Medically stable, assessed by a stroke physician.
* Sufficient English language comprehension and cognitive ability to understand the study protocol, follow instructions, complete questionnaires and give informed consent.
* Ability to mobilise lower body limbs in a cyclical manner (at least one leg).
* Likely to be admitted to the Royal Hallamshire Hospital for at least 7 days.

Exclusion Criteria:

* Haemorrhagic stroke.
* \<1 day or \>7 days after onset of stroke symptoms.
* Clinically unstable, assessed by stroke physician.
* Disability preventing unipedal cycling.
* New York Heart Failure Classification stage III/IV.
* Terminal illness (life expectancy \<6 months).
* Resting blood pressure \>180/110 mmHg.
* Uncontrolled arrhythmia causing symptoms or haemodynamic compromise.
* Unstable angina.
* Uncontrolled diabetes mellitus.
* Acute deep vein thrombosis, pulmonary embolism or pulmonary infection.
* Already participating in a clinical research trial.
* Pain during mobilisation of lower-limbs.
* Lower-limb spasticity or contracture which impairs ability to cycle.

Primary outcomes:
measure: Safety of aerobic exercise training
timeFrame: 21 months
measure: Acceptability of aerobic exercise training
timeFrame: 18 months
Secondary outcomes:
measure: Feasibility of recruitment
timeFrame: 18 months
measure: Feasibility of data collection
timeFrame: 21 months
Other outcomes:
measure: Rectus femoris cross sectional area
timeFrame: Baseline, 1 week and 3 months
measure: Rectus femoris muscle thickness
timeFrame: Baseline, 1 week and 3 months
measure: Vastus lateralis muscle thickness
timeFrame: Baseline, 1 week and 3 months
measure: Vastus lateralis angle of pennation
timeFrame: Baseline, 1 week and 3 months
measure: Cognitive function
timeFrame: Baseline, 3 months
measure: Anxiety and depression
timeFrame: 1 week, 3 months
measure: Optimism
timeFrame: Baseline, 3 months
measure: Exercise self-efficacy
timeFrame: Baseline, 1 week and 3 months
measure: Health-related quality of life
timeFrame: Baseline, 3 months
measure: Inpatient physical activity levels
timeFrame: Worn for 1 week in hospital
measure: Post-discharge physical activity levels (short-term)
timeFrame: Worn for 2 weeks post-discharge
measure: Post-discharge physical activity levels (long-term)
timeFrame: 3 months
measure: Chronic fatigue
timeFrame: Baseline, 3 months
measure: Lower-extremity function
timeFrame: Baseline, 1 week and 3 months
measure: Upper-extremity function
timeFrame: Baseline, 1 week and 3 months
measure: Disability
timeFrame: Baseline and 3 months
measure: Functional independence
timeFrame: Baseline, 4-8 weeks, 3 months
measure: Aerobic exercise-induced changes in cerebral blood flow velocity
timeFrame: Day 5 or 6 (measured for approximately 1 hour during exercise session)
measure: Aerobic exercise-induced changes in mature brain-derived neurotrophic factor (BDNF)
timeFrame: Day 5 or 6 (pre-post exercise)
Locations:
city: Sheffield
country: United Kingdom
facility: Royal Hallamshire Hospital
state: South Yorkshire
Study officials:
affiliation: Sheffield Hallam University
name: Tom Maden-Wilkinson, PhD
role: PRINCIPAL_INVESTIGATOR
References: