Effects rTMS Combined With Fluoxetine on Motor Recovery in Stroke Patients

Study Overview
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Brief Summary
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In this study investigator's aim to assess the effect of a type of non-invasive brain stimulation technique called repetitive transcranial magnetic stimulation (rTMS) in conjunction with fluoxetine on motor recovery after stroke.

Official Title
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Effects of Contralesional Repetitive Magnetic Stimulation Combined With Fluoxetine on Motor Recovery in Acute Stroke Patients

Conditions
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Stroke, Motor Function

Intervention / Treatment
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* Device: Active Repetitive Transcranial Magnetic Stimulation (rTMS)
* Drug: Fluoxetine
* Device: Sham repetitive transcranial magnetic stimulation (rTMS)
* Drug: Placebo Fluoxetine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ischemic infarction within the past 2 years post event that has caused hemiparesis or hemiplegia, as self-reported and/or confirmed by medical record. Older than 18 years old. Upper extremity weakness defined as a score of >11 and ≤56 on the arm motor Fugl-Mayer motor scale. Minimal pre-stroke disability defined as a score of <3 in the Modified Rankin Scale. Subjects need to be able to follow directions and participate in 2 hours of testing with short breaks. Subjects need to be able to provide informed consent. Exclusion Criteria: Any substantial decrease in alertness, language reception, or attention that might interfere with understanding instruction for motor testing Excessive pain in any joint of the paretic extremity (not applicable to severe stroke subjects), as self reported Contraindications to single pulse TMS (will be used to measure cortical excitability) such as: history of seizures, unexplained loss of consciousness, any metal implants in the head, frequent or severe headaches or neck pain, any other electronic implanted medical devices such as pacemakers, defibrillators, or implant medication pump. Patients who have taken fluoxetine in the past 5 weeks. Patients taking any other SSRI at the time of enrollment or in the previous month. Patients taking any other medication likely to have adverse interaction with SSRIs (all the medications the patient is taking will be carefully reviewed, as noted below in Monitoring of important drug interactions). Active depression on admission to SRH defined by a score of 24 or higher in the Hamilton Depression Rating Scale (HAM-D) Concurrent medical condition likely to worsen patient's functional status in the next 6 months such as: cancer, terminal heart, kidney or liver disease, as self-reported and/or confirmed by medical record. Pregnancy.

Ages Eligible for Study
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Minimum Age: 18 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active rTMS/active fluoxetine<br>Subjects in this arm will undergo 10 daily sessions over 15 days of active low-frequency rTMS with each session lasting 20 minutes. This will be followed by 8 weekly sessions of active low-frequency rTMS with each session lasting 20 minutes. Additionally, during this time beginning with enrollment, subjects will also be taking 20mg of active fluoxetine by mouth daily. | Device: Active Repetitive Transcranial Magnetic Stimulation (rTMS)<br>* Subjects will undergo active low-frequency rTMS (1Hz continuous). Each session will last 20 minutes and will be conducted at 100% of the motor threshold.<br>* Other names: magnetic stimulation, Magstim;Drug: Fluoxetine<br>* Subjects will receive active fluoxetine (20mg) and take orally consecutively for 90 days.<br>* Other names: Prozac, Sarafem, Ladose, Fontex;|
| Experimental: Sham rTMS/active fluoxetine<br>Subjects in this arm will undergo 10 daily sessions over 15 days of sham low-frequency rTMS with each session lasting 20 minutes. This will be followed by 8 weekly sessions of sham low-frequency rTMS with each session lasting 20 minutes. Additionally, during this time beginning with enrollment, subjects will also be taking 20mg of active fluoxetine by mouth daily. | Drug: Fluoxetine<br>* Subjects will receive active fluoxetine (20mg) and take orally consecutively for 90 days.<br>* Other names: Prozac, Sarafem, Ladose, Fontex;Device: Sham repetitive transcranial magnetic stimulation (rTMS)<br>* Subjects will undergo sham low-frequency rTMS (using sham coil). This session will last 20 minutes, just as the active session would, however, no magnetic pulses will be delivered.<br>* Other names: Magstim, magnetic stimulation;|
| Experimental: Sham rTMS/placebo fluoxetine<br>Subjects in this arm will undergo 10 daily sessions over 15 days of sham low-frequency rTMS with each session lasting 20 minutes. This will be followed by 8 weekly sessions of sham low-frequency rTMS with each session lasting 20 minutes. Additionally, during this time beginning with enrollment, subjects will also be taking 20mg of placebo fluoxetine by mouth daily. | Device: Sham repetitive transcranial magnetic stimulation (rTMS)<br>* Subjects will undergo sham low-frequency rTMS (using sham coil). This session will last 20 minutes, just as the active session would, however, no magnetic pulses will be delivered.<br>* Other names: Magstim, magnetic stimulation;Drug: Placebo Fluoxetine<br>* Subject will receive placebo fluoxetine (sugar pills) and will take orally consecutively for 90 days.<br>* Other names: Prozac, Sarafem, Ladose, Fontex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Motor Function (Jebsen-Taylor Task) | Jebsen Taylor Hand Function Test: measures hand function in real-life activities, by evaluating the time required to perform 7 different tasks. We used the non-constrained hand for the assessments. The sum of the different tasks was used for the analysis. Calculation details: value at 9 months minus value at baseline, change in seconds (adjusted mean difference). | baseline and 90 days | 
| Changes in Fugl-Meyer Assessment (FMA) Scale | The Fugl-Meyer Assessment (FMA) is a stroke-specific, performance-based impairment index. It is designed to assess motor functioning, balance, sensation, and joint functioning in patients with post-stroke hemiplegia. We used the upper limb motor function subscale: minimum values= 0 ; maximum values= 66. Higher scores mean a better outcome. Changes from baseline to 90 days (value at 90 days minus value at baseline). | baseline and 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Cortical Excitability Measures | We will measure cortical excitability using single-pulsed transcranial magnetic stimulation (TMS) before and after stimulation at three different time-points. Changes from baseline to 90 days (value at 90 days minus value at baseline). | Baseline and 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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repetitive transcranial magnetic stimulation, rTMS, TMS, fluoxetine