StrokePhase 2NCT02208466

Effects rTMS Combined With Fluoxetine on Motor Recovery in Stroke Patients

A Phase 2 study testing Active Repetitive Transcranial Magnetic Stimulation (rTMS) and Fluoxetine in people with Stroke and Motor Function, run by Spaulding Rehabilitation Hospital at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial 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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Stroke, Motor Function
What is being tested?: Active Repetitive Transcranial Magnetic Stimulation (rTMS) and Fluoxetine
Type of treatment: Pill or oral medicine, Medical device
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 44 participants
Where: 1 siteUnited States
Study dates: Sep 2014to 25 Jun 2019
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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").

Show all 9Show fewer

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.

Trial locations and contacts

1 site in 1 country.

United States1 site

Spaulding Rehabilitation Hospital
Charlestown, Massachusetts, 02129

Other trials in United States

About this study

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

Conditions: Stroke, Motor Function
Being tested: Active Repetitive Transcranial Magnetic Stimulation (rTMS), Fluoxetine, Sham repetitive transcranial magnetic stimulation (rTMS), Placebo Fluoxetine
Keywords: repetitive transcranial magnetic stimulation, rTMS, TMS, fluoxetine
Medical subject headings: Stroke

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Active Repetitive Transcranial Magnetic Stimulation (rTMS)Device
Also called magnetic stimulation, Magstim
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.
FluoxetineDrug
Also called Prozac, Sarafem, Ladose, Fontex
Subjects will receive active fluoxetine (20mg) and take orally consecutively for 90 days.
Sham repetitive transcranial magnetic stimulation (rTMS)Device
Also called Magstim, magnetic stimulation
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 FluoxetineDrug
Also called Prozac, Sarafem, Ladose, Fontex
Subject will receive placebo fluoxetine (sugar pills) and will take orally consecutively for 90 days.

Study groups in NCT02208466
Study group	Role	What they receive
Active rTMS/active fluoxetine	Experimental	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. Receives: Device: Active Repetitive Transcranial Magnetic Stimulation (rTMS); Drug: Fluoxetine
Sham rTMS/active fluoxetine	Experimental	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. Receives: Drug: Fluoxetine; Device: Sham repetitive transcranial magnetic stimulation (rTMS)
Sham rTMS/placebo fluoxetine	Experimental	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. Receives: Device: Sham repetitive transcranial magnetic stimulation (rTMS); Drug: Placebo Fluoxetine

What is being measured

The primary outcome is the main question the study is designed to answer.

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).
Measured: 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).
Measured: baseline and 90 days

Secondary outcomes (1)

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).
Measured: Baseline and 90 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 201425 Jun 2019

First posted5 Aug 2014 (estimated)
Study startSep 2014
Primary completion25 Jun 2019
Study completion25 Jun 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for StrokeStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 44 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02208466
Sponsor's protocol ID: 2014P001046
Status last verified: Feb 2021
First submitted: 28 Jul 2014
Last updated: 21 Feb 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Bonin Pinto C, Morales-Quezada L, de Toledo Piza PV, Zeng D, Saleh Velez FG, Ferreira IS, Lucena PH, Duarte D, Lopes F, El-Hagrassy MM, Rizzo LV, Camargo EC, Lin DJ, Mazwi N, Wang QM, Black-Schaffer R, Fregni F. Combining Fluoxetine and rTMS in Poststroke Motor Recovery: A Placebo-Controlled Double-Blind Randomized Phase 2 Clinical Trial. Neurorehabil Neural Repair. 2019 Aug;33(8):643-655. doi: 10.1177/1545968319860483. Epub 2019 Jul 9.
PubMed 31286828

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruiting
Temporal Interference Stimulation for Upper-Limb Motor Recovery in Early Subacute Stroke
Acute Ischemic Stroke
RecruitingObservational study
ELATE Study: Evaluating Large-vessel Acute Thrombectomy in Extended Time Window
Acute Ichemic Stroke
Recruiting
Web-Based Tele-Rehabilitation Using Action Observation and Mirror Therapy for Subacute Stroke: A Randomized Controlled Trial
Stroke, Upper Extremity Paresis
Recruiting
Early Motor-Cognitive Integrative Training on Cognitive and Motor Performance in Patients With Aneurysmal Subarachnoid Hemorrhage
Subarachnoid Aneurysm Hemorrhage
Not yet recruiting
Selective Intra-Arterial Hypothermia After Endovascular Treatment for Acute Basilar Artery Occlusion
Acute Ischemic Stroke, Basilar Artery Occlusion

All Stroke trials

Study at a glance

From the registry record, last updated by the sponsor on 21 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Effects of Contralesional Repetitive Magnetic Stimulation Combined With Fluoxetine on Motor Recovery in Acute Stroke Patients
ClinicalTrials.gov ID: NCT02208466
Acronym / sponsor ID: 2014P001046
Conditions: Stroke, Motor Function
Keywords: repetitive transcranial magnetic stimulation, rTMS, TMS, fluoxetine
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 44 participants (actual)
Lead sponsor: Spaulding Rehabilitation HospitalUniversity, hospital or other
Study start: Sep 2014
Primary completion: 25 Jun 2019 (actual)
Study completion: 25 Jun 2019 (actual)
First posted: 5 Aug 2014 (estimated)
Results: Posted 21 Feb 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 3

Arm	Type	Receives
Active rTMS/active fluoxetine	Experimental	Device: Active Repetitive Transcranial Magnetic Stimulation (rTMS), Drug: FluoxetineSubjects 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.
Sham rTMS/active fluoxetine	Experimental	Drug: Fluoxetine, Device: Sham repetitive transcranial magnetic stimulation (rTMS)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.
Sham rTMS/placebo fluoxetine	Experimental	Device: Sham repetitive transcranial magnetic stimulation (rTMS), Drug: Placebo FluoxetineSubjects 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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

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.

Key exclusion criteria (9 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Active Repetitive Transcranial Magnetic Stimulation (rTMS)Also: magnetic stimulation, MagstimSubjects will undergo active low-frequency rTMS (1Hz continuous). Each session will last 20 minutes and will be conducted at 100% of the motor threshold.	Device	Active rTMS/active fluoxetine
FluoxetineAlso: Prozac, Sarafem, Ladose, FontexSubjects will receive active fluoxetine (20mg) and take orally consecutively for 90 days.	Drug	Active rTMS/active fluoxetine, Sham rTMS/active fluoxetine
Sham repetitive transcranial magnetic stimulation (rTMS)Also: Magstim, magnetic stimulationSubjects 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.	Device	Sham rTMS/active fluoxetine, Sham rTMS/placebo fluoxetine
Placebo FluoxetineAlso: Prozac, Sarafem, Ladose, FontexSubject will receive placebo fluoxetine (sugar pills) and will take orally consecutively for 90 days.	Drug	Sham rTMS/placebo fluoxetine

Primary outcome

Changes in Motor Function (Jebsen-Taylor Task)
Time frame: 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
Time frame: 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).

1 secondary outcome

Changes in Cortical Excitability Measures
Time frame: Baseline and 90 days

Results and safety

Results posted to the registry on 21 Feb 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Active rTMS/Active Fluoxetine	9	9
Sham rTMS/Active Fluoxetine	10	10
Sham rTMS/Placebo Fluoxetine	8	8

Primary outcome: Changes in Motor Function (Jebsen-Taylor Task)

Time frame: baseline and 90 days. Mean (95% Confidence Interval). Unit: seconds

Measure	Active rTMS/Active Fluoxetine n = 9	Sham rTMS/Active Fluoxetine n = 10	Sham rTMS/Placebo Fluoxetine n = 8
Value	-214.33 (-289.32 to -139.35)	-50.16 (-110.56 to -10.24)	-117.98 (-197.39 to -38.58)

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

Primary outcome: Changes in Fugl-Meyer Assessment (FMA) Scale

Time frame: baseline and 90 days. Mean (95% Confidence Interval). Unit: units on a scale

Measure	Active rTMS/Active Fluoxetine n = 9	Sham rTMS/Active Fluoxetine n = 10	Sham rTMS/Placebo Fluoxetine n = 8
Value	10.10 (4.06 to 16.14)	6.73 (1.28 to 12.17)	15.55 (9.16 to 21.95)

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

1 secondary outcome is reported in the full results.

Adverse events

Time frame: 3 months. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Active rTMS/Active Fluoxetine	0 of 9 (0%)	2 of 9 (22.2%)	0 of 9
Sham rTMS/Active Fluoxetine	0 of 10 (0%)	0 of 10 (0%)	0 of 10
Sham rTMS/Placebo Fluoxetine	0 of 8 (0%)	3 of 8 (37.5%)	0 of 8

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 31286828Bonin Pinto C, Morales-Quezada L, de Toledo Piza PV, Zeng D, Saleh Velez FG, Ferreira IS, Lucena PH, Duarte D, Lopes F, El-Hagrassy MM, Rizzo LV, Camargo EC, Lin DJ, Mazwi N, Wang QM, Black-Schaffer R, Fregni F. Combining Fluoxetine and rTMS in Poststroke Motor Recovery: A Placebo-Controlled Double-Blind Randomized Phase 2 Clinical Trial. Neurorehabil Neural Repair. 2019 Aug;33(8):643-655. doi: 10.1177/1545968319860483. Epub 2019 Jul 9.

Related trials for Stroke

Not yet recruiting
Temporal Interference Stimulation for Upper-Limb Motor Recovery in Early Subacute Stroke
Acute Ischemic Stroke
RecruitingObservational study
ELATE Study: Evaluating Large-vessel Acute Thrombectomy in Extended Time Window
Acute Ichemic Stroke
Recruiting
Web-Based Tele-Rehabilitation Using Action Observation and Mirror Therapy for Subacute Stroke: A Randomized Controlled Trial
Stroke, Upper Extremity Paresis
Recruiting
Early Motor-Cognitive Integrative Training on Cognitive and Motor Performance in Patients With Aneurysmal Subarachnoid Hemorrhage
Subarachnoid Aneurysm Hemorrhage
Not yet recruiting
Selective Intra-Arterial Hypothermia After Endovascular Treatment for Acute Basilar Artery Occlusion
Acute Ischemic Stroke, Basilar Artery Occlusion

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Felipe Fregni, MD PhD MPH principal investigator

Spaulding Rehabilitation Hospital

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Feb 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Changes in Motor Function (Jebsen-Taylor Task) (time frame: baseline and 90 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02208466, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Feb 2021.