Structural Neuroplasticity Associated With Aerobic Treadmill Training in Geriatric Chronic Stroke Survivors

Aerobic treadmill exercise has been shown to improve walking, cardiovascular fitness and thereby risk factor profiles in chronic stroke patients (Macko et al., Stroke 2005). The proposed project is a randomized controlled trial in geriatric stroke patients with chronic disabilities to investigate potential mechanisms of treadmill therapy. The hypothesis is tested that 3-months of aerobic treadmill exercise induces structural brain plasticity and reorganization. The outcome measures are walking ability, gait pattern, cardiovascular fitness and brain morphology. This study will elucidate fundamental mechanisms of brain adaptations linked to task-repetitive aerobic lower extremity exercise. These mechanisms will not only lead to a better understanding but may also help to identify predictors of treatment response.

40 patients aged over 60 years with lower extremity paresis after a first-ever clinical stroke longer than 6 months prior to study inclusion will be recruited from: 1) The Geriatric Rehabilitation Clinic at the Robert-Bosch Hospital in Stuttgart 2) the Dept of Neurology, University Hospital in Tübingen. Subjects will be randomized to 3 months progressive graded aerobic treadmill exercise training (TAEX; 3 times/week, duration 10-45 min) or an attention control group (CON). Because we expect that localization and size of stroke affect therapy outcomes, stratified randomization will be used to balance entry into groups.

We hypothesize that 3 months of treadmill gait training but not conventional care leads to improvements of cardiovascular fitness and gait and to brain reorganization (structural plasticity) in regions in which functional adaptations have been demonstrated using fMRI in previous studies. The specific aims are:

• To assess reorganization by comparing cortical thickness, cortical density and fiber tract morphology before (time point 0), and after therapy (3 months) using T1-weighted 3D-MPRAGE images, voxel based morphometry and diffusion tensor imaging.
• To correlate brain reorganization with improvements in walking velocity, and analysis of gait patterns (parameters, swing time, stance time, gait symmetry).
• To correlate brain reorganization with location and size of the index stroke lesion and of diffuse white matter damage (subcortical vascular encephalopathy). Lesion and white matter damage will be evaluated based on T2-weighted FLAIR sequences.

Study Overview

• Status: Completed
• Conditions: Stroke; Hemiparesis
• Intervention / Treatment: Behavioral: treadmill exercise training

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• women and men aged > 60 years
• first ever ischemic stroke at least prior 6 months
• all conventional inpatient and outpatient physical therapy completed
• residual hemiparetic gait disturbance adequate language and neurocognitive function to participate in exercise training and testing

Exclusion Criteria:

• already performing > 20 minutes aerobic exercise 3 X/ week
• Alcohol consumption >2 oz liquor, or 2x 4oz glasses of wine, or 2x 12 oz cans of beer per day.

• Cardiac history of

  1. unstable angina
  2. recent (< 3 months) myocardial infarction
  3. congestive heart failure (NYHA category II)
  4. hemodynamically significant valvular dysfunction.

• Medical History:

  1. recent hospitalization (<3 months) for severe medical disease
  2. symptomatic peripheral arterial occlusive disease
  3. orthopedic or chronic pain conditions restricting exercise
  4. pulmonary or renal failure
  5. active cancer
  6. poorly controlled hypertension (>160/100) or diabetes mellitis (fasting glucose>180 mg/dl, HbA1C >10%)

• Neurological history of

  1. dementia
  2. receptive or global aphasia that confounds testing and training, operationally defined as unable to follow 2 point commands
  3. cognitive deficits (other than dementia and aphasia, as above)

  (e) non-stroke neuromuscular disorder restricting exercise (eg Parkinson's Syndrome) (f) untreated major depression

• exclusion criteria for MRI scanning (metal implants (e.g. pacemaker), claustrophobia, etc.)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A; Treadmill training group (TAEX)	Behavioral: treadmill exercise training; 3 months (3 times/week) progressive graded aerobic treadmill training with a duration of 10-45 min per training session
Active Comparator: B; Attention control group (CON)	Behavioral: treadmill exercise training; 3 months (3 times/week) progressive graded aerobic treadmill training with a duration of 10-45 min per training session

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
aerobic capacity (peak VO2)	Baseline (timepoint 0) and after training (3 months)
gait velocity	Baseline (timepoint 0) and after training (3 months)

Secondary Outcome Measures

Outcome Measure	Time Frame
cortical thickness (MRI)	Baseline (timepoint 0) and after training (3 months)
grey matter density (VBM-MRI)	Baseline (timepoint 0) and after training (3 months)
cerebrovascular reserve capacity (ASL-MRI)	Baseline (timepoint 0) and after training (3 months)

Collaborators and Investigators

• Sponsor: Andreas R Luft
• Collaborators: Robert Bosch Medical Center; Max-Planck-Institute Tuebingen

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Actual): January 1, 2010
• Study Completion (Actual): April 1, 2010

Study Registration Dates

• First Submitted: January 31, 2008
• First Submitted That Met QC Criteria: January 31, 2008
• First Posted (Estimate): February 13, 2008

Study Record Updates

• Last Update Posted (Estimate): May 28, 2015
• Last Update Submitted That Met QC Criteria: May 27, 2015
• Last Verified: January 1, 2008

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Stroke; Paresis
• Other Study ID Numbers: BOSCH-TAEX-001