Enhancement of Post-stroke Neural Plasticity with Atomoxetine: A Pilot Study

Lumy Sawaki, MD, PhD, University of Kentucky, Physical Medicine &Rehabilitation Department, Cardinal Hill Endowed Chair

In the present application, we propose to evaluate whether treatment with atomoxetine, when combined with motor training, will improve motor function compared to physical therapy plus a placebo. This information is crucial in order to provide preliminary data that would support a large clinical trial of the effects of atomoxetine to enhance motor recovery and ultimately help patients who are recovering from a stroke in the future.

The long-range goals are to: (a) maximize the restoration of hand motor function after stroke, and (b) determine the impact of this intervention in activities of daily living and quality of life.

The central hypothesis is that stroke patients treated with atomoxetine paired with task-oriented therapy will have improved motor function compared to patients receiving therapy plus placebo, and the degree of this behaviorally-measured effect will correlate with the increase of training-dependent cortical plasticity measured by transcranial magnetic stimulation (TMS).

Specific Aim #1: Test the effects of atomoxetine paired with task-oriented therapy on hand motor function of stroke patients, measured by the Fugl-Meyer Assessment Scale.
The working hypothesis for this aim is:

• The ability of atomoxetine to inhibit norepinephrine reuptake will lead to a higher score for the paretic hand on the Fugl-Meyer Assessment Scale, compared to a control group receiving placebo paired with task-oriented therapy.

Specific Aim #2: Test the effect of atomoxetine paired with task-oriented therapy on the motor map of a specific muscle (extensor digitorum communis muscle), measured by TMS. The working hypothesis for this aim is:

• Atomoxetine and training of the paretic hand will lead to an increase in the TMS motor map of the relevant motor cortex, compared to a control group receiving placebo paired with task-oriented therapy.

Specific Aim #3: Evaluate the cardiovascular impact and other side effects of atomoxetine in stroke patients.The working hypothesis for this aim is:

• Atomoxetine will yield similar changes in blood pressure and heart rate compared to placebo and therefore further supporting the safety of this medication in this specific population.