Motor Function, Stroke
Conditions
Keywords
repetitive transcranial magnetic stimulation, rTMS, TMS, fluoxetine
Brief summary
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.
Interventions
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.
DRUGFluoxetine
Subjects will receive active fluoxetine (20mg) and take orally consecutively for 90 days.
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.
DRUGPlacebo Fluoxetine
Subject will receive placebo fluoxetine (sugar pills) and will take orally consecutively for 90 days.
Sponsors
Spaulding Rehabilitation Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Motor Function (Jebsen-Taylor Task) | baseline and 90 days | 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). |
| Changes in Fugl-Meyer Assessment (FMA) Scale | baseline and 90 days | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Cortical Excitability Measures | Baseline and 90 days | 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). |
Countries
United States
Participant flow
Pre-assignment details
Please note that from the 44 subjects enrolled, only 27 started (were randomized) as 17 subjects screened out during confirmation of eligibility after signing the consent form (some of the criteria could only be checked after consent).
Participants by arm
| Arm | Count |
|---|---|
| Active rTMS/Active Fluoxetine 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.
Active Repetitive Transcranial Magnetic Stimulation (rTMS): 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.
Fluoxetine: Subjects will receive active fluoxetine (20mg) and take orally consecutively for 90 days. | 9 |
| Sham rTMS/Active Fluoxetine 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.
Fluoxetine: Subjects will receive active fluoxetine (20mg) and take orally consecutively for 90 days.
Sham repetitive transcranial magnetic stimulation (rTMS): 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. | 10 |
| Sham rTMS/Placebo Fluoxetine 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.
Sham repetitive transcranial magnetic stimulation (rTMS): 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.
Placebo Fluoxetine: Subject will receive placebo fluoxetine (sugar pills) and will take orally consecutively for 90 days. | 8 |
| Total | 27 |
Baseline characteristics
| Characteristic | Active rTMS/Active Fluoxetine | Sham rTMS/Active Fluoxetine | Sham rTMS/Placebo Fluoxetine | Total |
|---|---|---|---|---|
| Age, Continuous | 57.22 years STANDARD_DEVIATION 9.39 | 50.5 years STANDARD_DEVIATION 16.57 | 57.38 years STANDARD_DEVIATION 9.96 | 55.03 years STANDARD_DEVIATION 11.97 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 9 Participants | 5 Participants | 22 Participants |
| Sex: Female, Male Female | 4 Participants | 5 Participants | 2 Participants | 11 Participants |
| Sex: Female, Male Male | 5 Participants | 5 Participants | 6 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 10 | 0 / 8 |
| other Total, other adverse events | 2 / 9 | 0 / 10 | 3 / 8 |
| serious Total, serious adverse events | 0 / 9 | 0 / 10 | 0 / 8 |
Outcome results
Primary
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).
Time frame: baseline and 90 days
Population: Performed by a rater blinded to rTMS and pharmacotherapy performed all assessments
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Active rTMS/Active Fluoxetine | Changes in Fugl-Meyer Assessment (FMA) Scale | 10.10 units on a scale |
| Sham rTMS/Active Fluoxetine | Changes in Fugl-Meyer Assessment (FMA) Scale | 6.73 units on a scale |
| Sham rTMS/Placebo Fluoxetine | Changes in Fugl-Meyer Assessment (FMA) Scale | 15.55 units on a scale |
Primary
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).
Time frame: baseline and 90 days
Population: Performed by a rater blinded to rTMS and pharmacotherapy performed all assessments
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Active rTMS/Active Fluoxetine | Changes in Motor Function (Jebsen-Taylor Task) | -214.33 seconds |
| Sham rTMS/Active Fluoxetine | Changes in Motor Function (Jebsen-Taylor Task) | -50.16 seconds |
| Sham rTMS/Placebo Fluoxetine | Changes in Motor Function (Jebsen-Taylor Task) | -117.98 seconds |
Secondary
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).
Time frame: Baseline and 90 days
Population: Performed by a rater blinded to rTMS and pharmacotherapy performed all assessments
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Active rTMS/Active Fluoxetine | Changes in Cortical Excitability Measures | -0.05 motor evoked potential (mV) |
| Sham rTMS/Active Fluoxetine | Changes in Cortical Excitability Measures | -0.12 motor evoked potential (mV) |
| Sham rTMS/Placebo Fluoxetine | Changes in Cortical Excitability Measures | 0.33 motor evoked potential (mV) |