Post-stroke Neural Plasticity With Atomoxetine

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

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.

Study Overview

• Status: Completed
• Conditions: Atomoxetine Hydrochloride; Placebos
• Intervention / Treatment: Drug: Atomoxetine; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Atomoxetine with motor training; 40 mg atomoxetine paired with task-oriented therapy for 10 consecutive weekdays	Drug: 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.; Other Names: Strattera
Placebo Comparator: Placebo with motor training; Placebo capsules paired with task-oriented therapy for 10 consecutive weekdays	Drug: 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.; Other Names: Sham

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Lumy Sawaki

Publications and helpful links

General Publications

• Ward A, Carrico C, Powell E, Westgate PM, Nichols L, Fleischer A, Sawaki L. Safety and improvement of movement function after stroke with atomoxetine: A pilot randomized trial. Restor Neurol Neurosci. 2017;35(1):1-10. doi: 10.3233/RNN-160673.

Study record dates

Study Major Dates

• Study Start: November 1, 2006
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: May 27, 2016
• First Submitted That Met QC Criteria: June 1, 2016
• First Posted (Estimate): June 2, 2016

Study Record Updates

• Last Update Posted (Actual): August 14, 2017
• Last Update Submitted That Met QC Criteria: July 13, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: neuroplasticity; human; transcranial magnetic stimulation; motor recovery; motor training
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Adrenergic Uptake Inhibitors; Atomoxetine Hydrochloride
• Other Study ID Numbers: No ID

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No