Atomoxetine Hydrochloride, Placebos
Conditions
Keywords
motor training, motor recovery, human, neuroplasticity, transcranial magnetic stimulation
Brief summary
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
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.
Interventions
DRUGPlacebo
Subjects will receive a single daily oral dose of placebo. We will administer 2 hours/daily of motor training sixty minutes after drug intake.
DRUGAtomoxetine
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.
Sponsors
Lumy Sawaki
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Fugl Meyer Assessment | baseline, post-intervention, 1-month follow-up | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Action Arm Research Test (ARAT) | baseline, post-intervention, 1-month follow-up | 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. |
| Change in Wolf Motor Function Test (WMFT) | baseline, post-intervention, 1-month follow-up | 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. |
| Transcranial Magnetic Stimulation | Score change after 10 days of intervention compared to baseline; Score change after 1-month after the intervention compared to baseline | — |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Atomoxetine With Motor Training 40 mg atomoxetine paired with task-oriented therapy for 10 consecutive weekdays
Atomoxetine: 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. | 6 |
| Placebo With Motor Training Placebo capsules paired with task-oriented therapy for 10 consecutive weekdays
Placebo: Subjects will receive a single daily oral dose of placebo. We will administer 2 hours/daily of motor training sixty minutes after drug intake. | 6 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 0 |
Baseline characteristics
| Characteristic | Atomoxetine With Motor Training | Placebo With Motor Training | Total |
|---|---|---|---|
| Age, Continuous | 50.5 years STANDARD_DEVIATION 12.6 | 59.8 years STANDARD_DEVIATION 5.2 | 55.6 years STANDARD_DEVIATION 10.4 |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 6 | 0 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 |
Outcome results
Primary
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.
Time frame: baseline, post-intervention, 1-month follow-up
Population: 3 subjects in Atomoxetine group were lost to follow-up.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Atomoxetine With Motor Training | Change in Fugl Meyer Assessment | Post-intervention minus baseline | 9.3 units on a scale |
| Atomoxetine With Motor Training | Change in Fugl Meyer Assessment | 1-month follow-up minus baseline | 11.9 units on a scale |
| Placebo With Motor Training | Change in Fugl Meyer Assessment | Post-intervention minus baseline | 2.2 units on a scale |
| Placebo With Motor Training | Change in Fugl Meyer Assessment | 1-month follow-up minus baseline | 5.8 units on a scale |
Secondary
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.
Time frame: baseline, post-intervention, 1-month follow-up
Population: 3 subjects in the Atomoxetine group were lost to follow-up.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Atomoxetine With Motor Training | Change in Action Arm Research Test (ARAT) | Post-intervention minus baseline | 7.7 units on a scale |
| Atomoxetine With Motor Training | Change in Action Arm Research Test (ARAT) | 1-month follow-up minus baseline | 10.1 units on a scale |
| Placebo With Motor Training | Change in Action Arm Research Test (ARAT) | 1-month follow-up minus baseline | 6.5 units on a scale |
| Placebo With Motor Training | Change in Action Arm Research Test (ARAT) | Post-intervention minus baseline | 5.3 units on a scale |
Secondary
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.
Time frame: baseline, post-intervention, 1-month follow-up
Population: 3 subjects in the Atomoxetine group were lost to follow-up.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Atomoxetine With Motor Training | Change in Wolf Motor Function Test (WMFT) | Post-intervention minus baseline | -0.1 log(seconds) |
| Atomoxetine With Motor Training | Change in Wolf Motor Function Test (WMFT) | 1-month follow-up minus baseline | -0.11 log(seconds) |
| Placebo With Motor Training | Change in Wolf Motor Function Test (WMFT) | Post-intervention minus baseline | -0.19 log(seconds) |
| Placebo With Motor Training | Change in Wolf Motor Function Test (WMFT) | 1-month follow-up minus baseline | -0.2 log(seconds) |
Secondary
Transcranial Magnetic Stimulation
Time frame: Score change after 10 days of intervention compared to baseline; Score change after 1-month after the intervention compared to baseline
Population: This data is not available at this time, as a relocation occurred during the project. Data collected at the previous institution used different software and stored the data in a different format than is currently used. Therefore, reconciliation of this data is being attempted at this time.