Effects rTMS Combined With Fluoxetine on Motor Recovery in Stroke Patients
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: 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. |
Device: 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.
Other Names:
Drug: Fluoxetine
Subjects will receive active fluoxetine (20mg) and take orally consecutively for 90 days.
Other Names:
|
Experimental: 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. |
Drug: Fluoxetine
Subjects will receive active fluoxetine (20mg) and take orally consecutively for 90 days.
Other Names:
Device: 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.
Other Names:
|
Experimental: 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. |
Device: 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.
Other Names:
Drug: Placebo Fluoxetine
Subject will receive placebo fluoxetine (sugar pills) and will take orally consecutively for 90 days.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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).
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Spaulding Rehabilitation Hospital | Charlestown | Massachusetts | United States | 02129 |
Sponsors and Collaborators
- Spaulding Rehabilitation Hospital
Investigators
- Principal Investigator: Felipe Fregni, MD PhD MPH, Spaulding Rehabilitation Hospital
Study Documents (Full-Text)
More Information
Publications
None provided.- 2014P001046
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail | 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). |
Arm/Group Title | Active rTMS/Active Fluoxetine | Sham rTMS/Active Fluoxetine | Sham rTMS/Placebo Fluoxetine |
---|---|---|---|
Arm/Group Description | 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. | 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. | 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. |
Period Title: Overall Study | |||
STARTED | 9 | 10 | 8 |
COMPLETED | 9 | 10 | 8 |
NOT COMPLETED | 0 | 0 | 0 |
Baseline Characteristics
Arm/Group Title | Active rTMS/Active Fluoxetine | Sham rTMS/Active Fluoxetine | Sham rTMS/Placebo Fluoxetine | Total |
---|---|---|---|---|
Arm/Group Description | 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. | 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. | 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. | Total of all reporting groups |
Overall Participants | 9 | 10 | 8 | 27 |
Age (years) [Mean (Standard Deviation) ] | ||||
Mean (Standard Deviation) [years] |
57.22
(9.39)
|
50.5
(16.57)
|
57.38
(9.96)
|
55.03
(11.97)
|
Sex: Female, Male (Count of Participants) | ||||
Female |
4
44.4%
|
5
50%
|
2
25%
|
11
40.7%
|
Male |
5
55.6%
|
5
50%
|
6
75%
|
16
59.3%
|
Race (NIH/OMB) (Count of Participants) | ||||
American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Asian |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Black or African American |
1
11.1%
|
1
10%
|
3
37.5%
|
5
18.5%
|
White |
8
88.9%
|
9
90%
|
5
62.5%
|
22
81.5%
|
More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Outcome Measures
Title | Changes in Motor Function (Jebsen-Taylor Task) |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
Performed by a rater blinded to rTMS and pharmacotherapy performed all assessments |
Arm/Group Title | Active rTMS/Active Fluoxetine | Sham rTMS/Active Fluoxetine | Sham rTMS/Placebo Fluoxetine |
---|---|---|---|
Arm/Group Description | 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. | 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. | 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. |
Measure Participants | 9 | 10 | 8 |
Mean (95% Confidence Interval) [seconds] |
-214.33
|
-50.16
|
-117.98
|
Title | Changes in Fugl-Meyer Assessment (FMA) Scale |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
Performed by a rater blinded to rTMS and pharmacotherapy performed all assessments |
Arm/Group Title | Active rTMS/Active Fluoxetine | Sham rTMS/Active Fluoxetine | Sham rTMS/Placebo Fluoxetine |
---|---|---|---|
Arm/Group Description | 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. | 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. | 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. |
Measure Participants | 9 | 10 | 8 |
Mean (95% Confidence Interval) [units on a scale] |
10.10
|
6.73
|
15.55
|
Title | Changes in Cortical Excitability Measures |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
Performed by a rater blinded to rTMS and pharmacotherapy performed all assessments |
Arm/Group Title | Active rTMS/Active Fluoxetine | Sham rTMS/Active Fluoxetine | Sham rTMS/Placebo Fluoxetine |
---|---|---|---|
Arm/Group Description | 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. | 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. | 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. |
Measure Participants | 9 | 10 | 8 |
Mean (95% Confidence Interval) [motor evoked potential (mV)] |
-0.05
|
-0.12
|
0.33
|
Adverse Events
Time Frame | 3 months | |||||
---|---|---|---|---|---|---|
Adverse Event Reporting Description | adverse effects were collected with a questionnaire for adverse effects | |||||
Arm/Group Title | Active rTMS/Active Fluoxetine | Sham rTMS/Active Fluoxetine | Sham rTMS/Placebo Fluoxetine | |||
Arm/Group Description | 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. | 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. | 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. | |||
All Cause Mortality |
||||||
Active rTMS/Active Fluoxetine | Sham rTMS/Active Fluoxetine | Sham rTMS/Placebo Fluoxetine | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/9 (0%) | 0/10 (0%) | 0/8 (0%) | |||
Serious Adverse Events |
||||||
Active rTMS/Active Fluoxetine | Sham rTMS/Active Fluoxetine | Sham rTMS/Placebo Fluoxetine | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/9 (0%) | 0/10 (0%) | 0/8 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
Active rTMS/Active Fluoxetine | Sham rTMS/Active Fluoxetine | Sham rTMS/Placebo Fluoxetine | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 2/9 (22.2%) | 0/10 (0%) | 3/8 (37.5%) | |||
Nervous system disorders | ||||||
Headache | 2/9 (22.2%) | 3 | 0/10 (0%) | 0 | 3/8 (37.5%) | 6 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | Dr. Felipe Fregni |
---|---|
Organization | Spaulding Rehabilitation Hospital |
Phone | 6179526158 |
fregni.felipe@mgh.harvard.edu |
- 2014P001046