Post-stroke Neural Plasticity With Atomoxetine

Study Overview
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Brief Summary
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This proposal evaluates the safety and effectiveness of a noradrenergic drug named atomoxetine combined with motor training to enhance cortical plasticity and improve hand function after stroke.

Detailed Description
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Extensive studies in laboratory animals and humans over the last ten years indicate that some medications, especially amphetamine, given with specific physical therapy may improve motor learning (and therefore recovery from stroke) more than physical therapy alone. However, the number of patients in clinical trials who have received physical therapy and amphetamine is very small, for two reasons: because amphetamine may interact with many other medications that stroke patients are already taking, and because its potential for addiction precludes its use on a daily basis. The investigators now wish to evaluate the effectiveness of a more selective medication, atomoxetine, known to have many fewer side effects and no potential for drug addiction. The proposed mechanism by which amphetamine enhances recovery is by increasing central levels of norepinephrine. While the investigators already know that this drug is more selective than amphetamine, the investigators would like to evaluate its effects on hand motor learning and motor recovery in chronic stroke patients in a clinical setting.

Official Title
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Enhancement of Post-stroke Neural Plasticity With Atomoxetine: a Pilot Study

Conditions
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Atomoxetine Hydrochloride, Placebos

Intervention / Treatment
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* Drug: Atomoxetine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic stroke patients Single stroke Chronic (more than 6 months after from stroke) At least 21 years old, but there is no upper age range for this project. Participants NOT able to extend the affected metacarpophalangeal joints at least 10° and the wrist 20°. Exclusion Criteria: History of head injury with loss of consciousness History of severe alcohol or drug abuse History of psychiatric illness Unstable cardiac dysrhythmia High blood pressure (systolic pressure >160 mm Hg and/or diastolic pressure >100 mm Hg) History of myocardial infarction or unstable angina Pregnancy Glaucoma, history of hypersensitivity or idiosyncrasy to sympathomimetic drugs. Subjects using drugs suspected of interfering with plasticity, such as MAOI, alpha-adrenergic antagonists, benzodiazepines, muscarinic receptor antagonists, dopaminergic antagonists, or other neuroleptics within 3 months of recruitment.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Atomoxetine with motor training<br>40 mg atomoxetine paired with task-oriented therapy for 10 consecutive weekdays | Drug: Atomoxetine<br>* Subjects will receive a single daily oral dose of 40 mg of atomoxetine. We will administer 2 hours/daily of motor training sixty minutes after drug intake.<br>* Other names: Strattera;|
| Placebo Comparator: Placebo with motor training<br>Placebo capsules paired with task-oriented therapy for 10 consecutive weekdays | Drug: Placebo<br>* Subjects will receive a single daily oral dose of placebo. We will administer 2 hours/daily of motor training sixty minutes after drug intake.<br>* Other names: Sham;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Fugl Meyer Assessment | Score after intervention minus baseline score, score at 1-month follow-up minus baseline score. The possible scores range from 0 to 66, with 66 indicating the best performance. | baseline, post-intervention, 1-month follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Action Arm Research Test (ARAT) | Score at post-intervention minus baseline, score at 1-month follow-up minus baseline. The score is calculated by summing the scores for 19 individual tasks. The possible scores range from 0 to 57, with higher scores indicating better performance. | baseline, post-intervention, 1-month follow-up | 
| Change in Wolf Motor Function Test (WMFT) | Score at post-intervention minus baseline, score at 1-month follow-up minus baseline. Each task is scored as amount of time taken to complete a task, which may range from just over 0 to 120 seconds. If the subject is unable to complete the task within 120 seconds, a score of 121 seconds is given. The scores from the 15 individual tasks are averaged, then the log is taken, resulting in the overall score. Therefore, the larger the score, the longer required to perform the tasks. Negative changes in score indicate that a subject, on average, was able to complete the tasks faster at post-intervention or at 1-month follow-up than at baseline. | baseline, post-intervention, 1-month follow-up | 
| Transcranial Magnetic Stimulation |  | Score change after 10 days of intervention compared to baseline; Score change after 1-month after the intervention compared to baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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transcranial magnetic stimulation, neuroplasticity, motor training, motor recovery, human