Trial Outcomes & Findings for Effects rTMS Combined With Fluoxetine on Motor Recovery in Stroke Patients (NCT NCT02208466)

NCT ID: NCT02208466

Last Updated: 2021-02-21

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

44 participants

Primary outcome timeframe

baseline and 90 days

Results posted on

2021-02-21

Participant Flow

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).

Participant milestones

Participant milestones
Measure	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.	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.	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.
Overall Study STARTED	9	10	8
Overall Study COMPLETED	9	10	8
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Effects rTMS Combined With Fluoxetine on Motor Recovery in Stroke Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Active rTMS/Active Fluoxetine n=9 Participants 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.	Sham rTMS/Active Fluoxetine n=10 Participants 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.	Sham rTMS/Placebo Fluoxetine n=8 Participants 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 n=27 Participants Total of all reporting groups
Age, Continuous	57.22 years STANDARD_DEVIATION 9.39 • n=5 Participants	50.5 years STANDARD_DEVIATION 16.57 • n=7 Participants	57.38 years STANDARD_DEVIATION 9.96 • n=5 Participants	55.03 years STANDARD_DEVIATION 11.97 • n=4 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	5 Participants n=7 Participants	2 Participants n=5 Participants	11 Participants n=4 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants	16 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	5 Participants n=4 Participants
Race (NIH/OMB) White	8 Participants n=5 Participants	9 Participants n=7 Participants	5 Participants n=5 Participants	22 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: baseline and 90 days

Population: Performed by a rater blinded to rTMS and pharmacotherapy performed all assessments

Outcome measures

Outcome measures
Measure	Active rTMS/Active Fluoxetine n=9 Participants 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.	Sham rTMS/Active Fluoxetine n=10 Participants 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.	Sham rTMS/Placebo Fluoxetine n=8 Participants 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.
Changes in Motor Function (Jebsen-Taylor Task)	-214.33 seconds Interval -289.32 to -139.35	-50.16 seconds Interval -110.56 to -10.24	-117.98 seconds Interval -197.39 to -38.58

PRIMARY outcome

Timeframe: baseline and 90 days

Population: Performed by a rater blinded to rTMS and pharmacotherapy performed all assessments

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).

Outcome measures

Outcome measures
Measure	Active rTMS/Active Fluoxetine n=9 Participants 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.	Sham rTMS/Active Fluoxetine n=10 Participants 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.	Sham rTMS/Placebo Fluoxetine n=8 Participants 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.
Changes in Fugl-Meyer Assessment (FMA) Scale	10.10 units on a scale Interval 4.06 to 16.14	6.73 units on a scale Interval 1.28 to 12.17	15.55 units on a scale Interval 9.16 to 21.95

SECONDARY outcome

Timeframe: Baseline and 90 days

Population: Performed by a rater blinded to rTMS and pharmacotherapy performed all assessments

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).

Outcome measures

Outcome measures
Measure	Active rTMS/Active Fluoxetine n=9 Participants 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.	Sham rTMS/Active Fluoxetine n=10 Participants 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.	Sham rTMS/Placebo Fluoxetine n=8 Participants 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.
Changes in Cortical Excitability Measures	-0.05 motor evoked potential (mV) Interval -0.34 to 0.08	-0.12 motor evoked potential (mV) Interval -0.33 to 0.43	0.33 motor evoked potential (mV) Interval 0.07 to 1.16

Adverse Events

Active rTMS/Active Fluoxetine

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Sham rTMS/Active Fluoxetine

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Sham rTMS/Placebo Fluoxetine

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Active rTMS/Active Fluoxetine n=9 participants at risk 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.	Sham rTMS/Active Fluoxetine n=10 participants at risk 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.	Sham rTMS/Placebo Fluoxetine n=8 participants at risk 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.
Nervous system disorders Headache	22.2% 2/9 • Number of events 3 • 3 months adverse effects were collected with a questionnaire for adverse effects	0.00% 0/10 • 3 months adverse effects were collected with a questionnaire for adverse effects	37.5% 3/8 • Number of events 6 • 3 months adverse effects were collected with a questionnaire for adverse effects

Additional Information

Dr. Felipe Fregni

Spaulding Rehabilitation Hospital

Phone: 6179526158

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place