StrokeNCT00929656
Combined Neural and Behavioral Therapies to Enhance Stroke Recovery
A study testing Real rTMS and Unimanual paretic UE Training in people with Stroke, run by VA Office of Research and Development at 1 site in United States.
Trial summary
Stroke is the leading cause of long-term disability in this country with more than 1 million Americans reporting difficulty with daily activities. Loss of independence in self-care tasks is primarily due to limited recovery of the arm. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Stroke
- What is being tested?
- Real rTMS and Unimanual paretic UE Training
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Feb 2013to 30 Sep 2015
- Phase
- Interventional
- 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of 1st stroke > 6 months
- Sub-cortical stroke confirmed with CT or MRI
- Passive range of motion in bilateral shoulder and elbow within functional limits
- UE Fugl-Meyer shoulder/elbow subcomponent score between 15 - 25
- 18-80 years of age
Who cannot join
- Use of medications that may lower seizure threshold
- History of epilepsy, brain tumor, learning disorder, mental retardation, drug or alcohol abuse, dementia, major head trauma, or major psychiatric illness
- evidence of epileptiform activity on EEG obtained before beginning treatment
- history or radiographic evidence of arteriovenous malformation, intracortical hemorrhage, subarachnoid hemorrhage, or bilateral cerebrovascular disease,
- history of cortical stroke
- history of implanted pacemaker or medication pump, metal plate in skull, or metal objects in the eye or skull
Show all 10Show fewer
- pregnancy
- pain in either upper extremity that would interfere with movement
- unable to understand 3-step directions
- orthopedic condition in back or UE or impaired corrected vision that would alter kinematics of reaching
Trial locations and contacts
1 site in 1 country.
United States1 site
North Florida/South Georgia Veterans Health System, Gainesville, FL
Gainesville, Florida, 32608
About this study
Official title: Combining Neural and Behavioral Therapies to Enhance Stroke Recovery
Stroke is the leading cause of long-term disability in this country with more than 1 million Americans reporting difficulty with daily activities. Loss of independence in self-care tasks is primarily due to limited recovery of the arm. This study will determine if the addition of Transcranial Magnetic Stimulation (TMS) to excite the lesioned hemisphere (side of the brain affected by the stroke), to progressive functional task exercise either of the weakened arm alone or of both arms together will improve arm recovery to a greater degree than one of these two types of arm exercise alone. Individuals post-stroke will participate in 16 sessions of 1) arm rehabilitation alone (with the weaker arm only or with both arms together) or 2) arm rehabilitation plus TMS. The investigators will assess arm movement ability and function immediately following the 4-week intervention and at a 30-day follow-up to determine retention of immediate gains. The investigators hypothesize that those who receive TMS as an adjuvant will have improved arm movement ability than those who only exercise.
Read the detailed description
Limited recovery of upper extremity (UE) function post-stroke continues to be one of the greatest challenges faced in neurorehabilitation. There is an urgent unmet need to identify effective approaches to drive UE recovery in this population. In response to this challenge, the overall purpose of this proposed research plan is to develop rehabilitation interventions that restore UE motor recovery. Contemporary approaches to motor rehabilitation are based on evidence that behavioral experience drives cortical reorganization following neural injury. Although the rationale of driving the damaged motor cortex by focused training of the paretic UE appears straightforward, and has historically been the focus of rehabilitation, functional recovery remains limited. There remains a gap between this central neurobiological change and a meaningful behavioral change. There is a need, therefore, to augment or potentiate behavioral experience. This proposal will address this gap by examining two potential drivers of the lesioned hemisphere: 1) the non-lesioned hemisphere via engagement of the unaffected UE in behavioral training and 2) stimulation of the lesioned hemisphere via repetitive Transcranial Magnetic Stimulation (rTMS). This proposal builds on the foundation of the applicant's previous work which suggested that the contralesional, intact, hemisphere could be used to drive the lesioned hemisphere through bimanual movement. Additionally, it is possible to drive the lesioned hemisphere externally using rTMS to enhance cortical stimulation. Thus, pairing externally-driven enhancement of cortical excitability with internally-driven activation of the intact hemisphere during bilateral movements could combine to further increase excitability in the lesioned hemisphere and manifest improved movement capability of the paretic UE. The fundamental hypothesis guiding this proposal is that increased excitability of the lesioned cortex will improve behavioral function of the paretic UE post-stroke. To investigate the overall hypothesis the investigators will examine these drivers of cortical excitability and their role in UE recovery by addressing the following aims:
Specific Aim 1. Determine the magnitude of difference in central and behavioral changes in individuals with post-stroke hemiparesis randomized to a bilateral versus unilateral UE motor training program.
Specific Aim 2a. Determine the magnitude of difference in central and behavioral changes in individuals with post-stroke hemiparesis randomized to behavioral UE training compared to behavioral UE training + rTMS.
Specific Aim 2b. Determine the differential effects of rTMS on bilateral behavioral training compared to unilateral behavioral training as measured both centrally and behaviorally in individuals with post-stroke hemiparesis Post-stroke upper limb paresis and resultant loss of functional ability continues to present a barrier to those post-stroke in returning to full societal participation. Interventions that directly target the mechanism of hemiparesis, including decreased excitability of the lesioned hemisphere, are most likely to promote true recovery as opposed to the oft observed functional compensation in these individuals.
- Conditions
- Stroke
- Being tested
- Real rTMS, Sham rTMS, Unimanual paretic UE Training
- Keywords
- Rehabilitation, Neurophysiology, Upper Extremity
- Medical subject headings
- Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Real rTMSProcedure or surgery
rTMS application to lesioned hemisphere; 10 Hz, 1000 pulses
Sham rTMSProcedure or surgery
sham rTMS application to lesioned hemisphere; 10 Hz, 1000 pulses
Unimanual paretic UE TrainingProcedure or surgery
UE exercise for 4 hours (two hours 1:1 with therapist and two hours independent at home) for 16 sessions (4 sessions/week for 4 weeks)
| Study group | Role | What they receive |
|---|---|---|
| Real rTMS | Experimental | Real rTMS + unimanual paretic UE training Receives: Procedure: Real rTMS; Procedure: Unimanual paretic UE Training |
| Sham rTMS | Active comparator | Sham rTMS + unimanual paretic UE training Receives: Procedure: Sham rTMS; Procedure: Unimanual paretic UE Training |
What is being measured
The primary outcome is the main question the study is designed to answer.
Wolf Motor Function Test Change
Change, in seconds, between Pre-intervention and post-intervention (4 wks following pre-intervention). The time to complete 15 separate upper extremity functional tasks are recorded. These 15 separate timed events are averaged to provide one time, in seconds. This is considered an Activity Measure on the WHO ICF model.
Measured: Change between Pre-intervention (baseline) to Post-intervention (4 wks following pre-intervention)
Secondary outcomes (4)
Upper Extremity Fugl-Meyer Motor Assessment Change
Change in Score from Pre-intervention to Post-Intervention. This outcome measures arm motor control; the ability to move outside of pathologic synergistic patterns. It is a measure of impairment in Body Structure/Function. Total score ranges from 0-66, with 0 indicative of no movement and 66 considered normal motor control.
Measured: Change Between Pre-intervention (baseline) to Post-intervention (4 wks following pre-intervention)
Grip Strength Change
Change in Paretic hand grip strength from pre- to post-intervention. Grip strength measured by hand-held dynamometer. An average of 3 5-second trials was used for analysis.
Measured: Change between Pre-intervention (baseline) to Post-intervention (4 wks following pre-intervention)
Motor Activity Log - Amount of Use Change
Self-Report Amount of Use of Paretic UE to complete 30 functional tasks. Each task is reported on a 0-5 scale with "0" representing "did not use my paretic hand at all for that task" and "5" representing "I used my paretic hand as much as before the stroke to complete that task." A "5" on each task would be considered "normal."
Measured: Change Between Pre-intervention (baseline) to Post-intervention (4 wks following pre-intervention)
Motor Activity Log - How Well Change
Self-Report of How Well paretic UE performed completing 30 functional tasks. Each task is reported on a 0-5 scale with "0" representing "Unable to use my paretic hand to perform that task" and "5" representing "My paretic hand performs that task as well as it did before the stroke." A "5" on each task would be considered "normal."
Measured: Change between Pre-intervention (baseline) to Post-intervention (4 wks following pre-intervention)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jun 2009 (estimated)
- Study start1 Feb 2013
- Primary completion30 Sep 2015
- Study completion30 Sep 2015
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.
- Other trials for StrokeStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Dorian Kay Rose, PhD MS BS, Principal investigator, North Florida/South Georgia Veterans Health System, Gainesville, FL
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00929656
- Sponsor's protocol ID
- B6862-W
- Status last verified
- Jul 2017
- First submitted
- 25 Jun 2009
- Last updated
- 21 Aug 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combining Neural and Behavioral Therapies to Enhance Stroke Recovery
- ClinicalTrials.gov ID
- NCT00929656
- Acronym / sponsor ID
- B6862-W
- Conditions
- Stroke
- Keywords
- Rehabilitation, Neurophysiology, Upper Extremity
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- 1 Feb 2013
- Primary completion
- 30 Sep 2015 (actual)
- Study completion
- 30 Sep 2015 (actual)
- First posted
- 29 Jun 2009 (estimated)
- Results
- Posted 5 Jul 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Stroke is the leading cause of long-term disability in this country with more than 1 million Americans reporting difficulty with daily activities. Loss of independence in self-care tasks is primarily due to limited recovery of the arm. This study will determine if the addition of Transcranial Magnetic Stimulation (TMS) to excite the lesioned hemisphere (side of the brain affected by the stroke), to progressive functional task exercise either of the weakened arm alone or of both arms together will improve arm recovery to a greater degree than one of these two types of arm exercise alone. Individuals post-stroke will participate in 16 sessions of 1) arm rehabilitation alone (with the weaker arm only or with both arms together) or 2) arm rehabilitation plus TMS. The investigators will assess arm movement ability and function immediately following the 4-week intervention and at a 30-day follow-up to determine retention of immediate gains. The investigators hypothesize that those who receive TMS as an adjuvant will have improved arm movement ability than those who only exercise.
Detailed description
Limited recovery of upper extremity (UE) function post-stroke continues to be one of the greatest challenges faced in neurorehabilitation. There is an urgent unmet need to identify effective approaches to drive UE recovery in this population. In response to this challenge, the overall purpose of this proposed research plan is to develop rehabilitation interventions that restore UE motor recovery. Contemporary approaches to motor rehabilitation are based on evidence that behavioral experience drives cortical reorganization following neural injury. Although the rationale of driving the damaged motor cortex by focused training of the paretic UE appears straightforward, and has historically been the focus of rehabilitation, functional recovery remains limited. There remains a gap between this central neurobiological change and a meaningful behavioral change. There is a need, therefore, to augment or potentiate behavioral experience. This proposal will address this gap by examining two potential drivers of the lesioned hemisphere: 1) the non-lesioned hemisphere via engagement of the unaffected UE in behavioral training and 2) stimulation of the lesioned hemisphere via repetitive Transcranial Magnetic Stimulation (rTMS). This proposal builds on the foundation of the applicant's previous work which suggested that the contralesional, intact, hemisphere could be used to drive the lesioned hemisphere through bimanual movement. Additionally, it is possible to drive the lesioned hemisphere externally using rTMS to enhance cortical stimulation. Thus, pairing externally-driven enhancement of cortical excitability with internally-driven activation of the intact hemisphere during bilateral movements could combine to further increase excitability in the lesioned hemisphere and manifest improved movement capability of the paretic UE. The fundamental hypothesis guiding this proposal is that increased excitability of the lesioned cortex will improve behavioral function of the paretic UE post-stroke. To investigate the overall hypothesis the investigators will examine these drivers of cortical excitability and their role in UE recovery by addressing the following aims:
Specific Aim 1. Determine the magnitude of difference in central and behavioral changes in individuals with post-stroke hemiparesis randomized to a bilateral versus unilateral UE motor training program.
Specific Aim 2a. Determine the magnitude of difference in central and behavioral changes in individuals with post-stroke hemiparesis randomized to behavioral UE training compared to behavioral UE training + rTMS.
Specific Aim 2b. Determine the differential effects of rTMS on bilateral behavioral training compared to unilateral behavioral training as measured both centrally and behaviorally in individuals with post-stroke hemiparesis Post-stroke upper limb paresis and resultant loss of functional ability continues to present a barrier to those post-stroke in returning to full societal participation. Interventions that directly target the mechanism of hemiparesis, including decreased excitability of the lesioned hemisphere, are most likely to promote true recovery as opposed to the oft observed functional compensation in these individuals.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Real rTMS | Experimental | Procedure: Real rTMS, Procedure: Unimanual paretic UE TrainingReal rTMS + unimanual paretic UE training |
| Sham rTMS | Active comparator | Procedure: Sham rTMS, Procedure: Unimanual paretic UE TrainingSham rTMS + unimanual paretic UE training |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Diagnosis of 1st stroke > 6 months
- Sub-cortical stroke confirmed with CT or MRI
- Passive range of motion in bilateral shoulder and elbow within functional limits
- UE Fugl-Meyer shoulder/elbow subcomponent score between 15 - 25
- 18-80 years of age
Key exclusion criteria (10 listed)
- Use of medications that may lower seizure threshold
- History of epilepsy, brain tumor, learning disorder, mental retardation, drug or alcohol abuse, dementia, major head trauma, or major psychiatric illness
- evidence of epileptiform activity on EEG obtained before beginning treatment
- history or radiographic evidence of arteriovenous malformation, intracortical hemorrhage, subarachnoid hemorrhage, or bilateral cerebrovascular disease,
- history of cortical stroke
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 |
|---|---|---|
| Real rTMSrTMS application to lesioned hemisphere; 10 Hz, 1000 pulses | Procedure or surgery | Real rTMS |
| Sham rTMSsham rTMS application to lesioned hemisphere; 10 Hz, 1000 pulses | Procedure or surgery | Sham rTMS |
| Unimanual paretic UE TrainingUE exercise for 4 hours (two hours 1:1 with therapist and two hours independent at home) for 16 sessions (4 sessions/week for 4 weeks) | Procedure or surgery | Real rTMS, Sham rTMS |
Primary outcome
Wolf Motor Function Test Change
Time frame: Change between Pre-intervention (baseline) to Post-intervention (4 wks following pre-intervention)
Change, in seconds, between Pre-intervention and post-intervention (4 wks following pre-intervention). The time to complete 15 separate upper extremity functional tasks are recorded. These 15 separate timed events are averaged to provide one time, in seconds. This is considered an Activity Measure on the WHO ICF model.
4 secondary outcomes
Upper Extremity Fugl-Meyer Motor Assessment Change
Time frame: Change Between Pre-intervention (baseline) to Post-intervention (4 wks following pre-intervention)
Grip Strength Change
Time frame: Change between Pre-intervention (baseline) to Post-intervention (4 wks following pre-intervention)
Motor Activity Log - Amount of Use Change
Time frame: Change Between Pre-intervention (baseline) to Post-intervention (4 wks following pre-intervention)
Motor Activity Log - How Well Change
Time frame: Change between Pre-intervention (baseline) to Post-intervention (4 wks following pre-intervention)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Stroke
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ELATE Study: Evaluating Large-vessel Acute Thrombectomy in Extended Time Window
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Web-Based Tele-Rehabilitation Using Action Observation and Mirror Therapy for Subacute Stroke: A Randomized Controlled Trial
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Early Motor-Cognitive Integrative Training on Cognitive and Motor Performance in Patients With Aneurysmal Subarachnoid Hemorrhage
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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.
Dorian Kay Rose, PhD MS BS principal investigator
North Florida/South Georgia Veterans Health System, Gainesville, FL
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Real rTMS and Unimanual paretic UE Training in people with Stroke, run by VA Office of Research and Development at 1 site in United States.
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 5 inclusion and 10 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 Aug 2017. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Jul 2017). 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?
Wolf Motor Function Test Change (time frame: Change between Pre-intervention (baseline) to Post-intervention (4 wks following pre-intervention)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 Aug 2017.