Exercise and Genotype in Sub-acute Stroke
Condition: Stroke
MeSH terms: Stroke
Study type: Interventional

Summary: 
      This study will investigate the impact of cardiovascular exercise on brain plasticity among
      patients in sub-acute stages after stroke, and whether genotype modulates the response to
      this intervention. Participants in the experimental group will perform cardiovascular
      training for 8 weeks, three times/week in addition to standard therapy, while participants in
      the control group will perform standard therapy only. Assessments will be performed at
      baseline, four weeks, and 8 weeks after training.
    

Detailed description: 
      Background: Research has shown that the adult human brain has an enormous plastic capacity to
      adapt after injury. In people who have recently experienced a stroke, interventions that
      promote brain plasticity in early stages after stroke can improve long-term recovery.
      Cardiovascular exercise is a simple strategy to increase brain plasticity and promote neural
      reorganization. However, there is no information about the effects of cardiovascular exercise
      on brain plasticity in early phases of stroke, despite the importance of this initial period
      for long-term recovery. Similarly, it is not known if, depending on their genetic profile,
      some people will be more responsive than others to this type of exercise.

      Objectives: To establish whether: 1) cardiovascular exercise improves brain plasticity during
      the initial phases of post-stroke recovery; 2) carrying a specific form of the BDNF gene
      modulates the response to cardiovascular exercise.

      Design: 70 participants will perform either a progressive high-intensity cardiovascular
      exercise program or low-intensity stretching and toning exercise program. Both groups will
      undergo 8 weeks of training performed 3 times per week. Assessments will be performed at the
      beginning, mid-point (4 weeks) and at the end of the training period (8 weeks).

      Methodology: Assessments: 1) brain plasticity by measuring changes in brain excitability, a
      marker of brain plasticity, with non-invasive brain stimulation; 2) BDNF levels by measuring
      the blood concentration of this protein; 3) Genotype by identifying the subtype of BDNF gene
      carried by each participant; 4) Cardiorespiratory fitness by assessing the performance during
      a graded exercise test.

      Statistical analysis: Differences between exercise and control groups on the primary endpoint
      of all outcomes will be analyzed with linear mixed models. Besides baseline scores, sex, age,
      and type of stroke (cortical or subcortical) will be included as covariates because they can
      affect brain plasticity and BDNF response. T1 scores will also be included to increase the
      efficiency of the model. The influence of genotype on changes in primary and secondary
      outcomes in the exercise group will be inspected with the Freedman-Schatzkin test, a powerful
      technique to identify mediators of change that can be used in small-scale exercise studies.

      Expected outcomes: Cardiovascular exercise will promote positive changes in brain
      excitability and will increase blood BDNF levels in individuals in the early phases of stroke
      recovery. However, the individual response to this type of exercise in relation to brain
      plasticity and BDNF levels will be influenced by the genotype of each participant.

      Relevance: It is important to establish whether cardiovascular exercise enhances brain
      reorganization early after stroke post-stroke and whether genetic factors may influence the
      response to this intervention. This will provide clinicians with useful information which
      will be essential to design more individualized exercise-based treatments to optimize
      functional recovery in individuals with stroke.

      Impact: The first weeks after a stroke are critical for functional recovery. After this
      initial period, the rate of recovery slows down and functional improvements become much more
      difficult to achieve. In Canada, health-care costs in the 6 months after stroke amount to
      $2.8 billion/year. Finding cost-effective rehabilitation strategies to promote recovery
      during the early phases post-stroke is essential to help patients return to an independent
      living.
    

Intervention name(s): Cardiovascular training; Standard Therapy
Intervention type(s): Behavioral; Behavioral
Intervention description(s): 8 weeks of cardiovascular training; 8 weeks of Standard Therapy
Other intervention name(s): CT; ST
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Stroke; Rehabilitation; Neurosciences; Exercise; Neuroplasticity; BDNF; Cardiovascular training; Motor function; HIIT; Genotype