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Effects rTMS Combined With Fluoxetine on Motor Recovery in Stroke Patients

Primary Purpose

Stroke, Motor Function

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Active Repetitive Transcranial Magnetic Stimulation (rTMS)
Fluoxetine
Sham repetitive transcranial magnetic stimulation (rTMS)
Placebo Fluoxetine
Sponsored by
Spaulding Rehabilitation Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Stroke focused on measuring repetitive transcranial magnetic stimulation, rTMS, TMS, fluoxetine

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Spaulding Rehabilitation Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Active rTMS/active fluoxetine

Sham rTMS/active fluoxetine

Sham rTMS/placebo fluoxetine

Arm 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.

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.

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.

Outcomes

Primary Outcome Measures

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).
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).

Secondary Outcome Measures

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).

Full Information

First Posted
July 28, 2014
Last Updated
February 2, 2021
Sponsor
Spaulding Rehabilitation Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT02208466
Brief Title
Effects rTMS Combined With Fluoxetine on Motor Recovery in Stroke Patients
Official Title
Effects of Contralesional Repetitive Magnetic Stimulation Combined With Fluoxetine on Motor Recovery in Acute Stroke Patients
Study Type
Interventional

2. Study Status

Record Verification Date
February 2021
Overall Recruitment Status
Completed
Study Start Date
September 2014 (undefined)
Primary Completion Date
June 25, 2019 (Actual)
Study Completion Date
June 25, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Spaulding Rehabilitation Hospital

4. Oversight

Data Monitoring Committee
No

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stroke, Motor Function
Keywords
repetitive transcranial magnetic stimulation, rTMS, TMS, fluoxetine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
44 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Active rTMS/active fluoxetine
Arm Type
Experimental
Arm 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.
Arm Title
Sham rTMS/active fluoxetine
Arm Type
Experimental
Arm Description
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.
Arm Title
Sham rTMS/placebo fluoxetine
Arm Type
Experimental
Arm Description
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.
Intervention Type
Device
Intervention Name(s)
Active Repetitive Transcranial Magnetic Stimulation (rTMS)
Other Intervention Name(s)
magnetic stimulation, Magstim
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Fluoxetine
Other Intervention Name(s)
Prozac, Sarafem, Ladose, Fontex
Intervention Description
Subjects will receive active fluoxetine (20mg) and take orally consecutively for 90 days.
Intervention Type
Device
Intervention Name(s)
Sham repetitive transcranial magnetic stimulation (rTMS)
Other Intervention Name(s)
Magstim, magnetic stimulation
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo Fluoxetine
Other Intervention Name(s)
Prozac, Sarafem, Ladose, Fontex
Intervention Description
Subject will receive placebo fluoxetine (sugar pills) and will take orally consecutively for 90 days.
Primary Outcome Measure Information:
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
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
Secondary Outcome Measure Information:
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Felipe Fregni, MD PhD MPH
Organizational Affiliation
Spaulding Rehabilitation Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Spaulding Rehabilitation Hospital
City
Charlestown
State/Province
Massachusetts
ZIP/Postal Code
02129
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
31286828
Citation
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.
Results Reference
derived

Learn more about this trial

Effects rTMS Combined With Fluoxetine on Motor Recovery in Stroke Patients

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