StrokePhase 1/2NCT01539096
Brain Stimulation-aided Stroke Rehabilitation: Neural Mechanisms of Recovery
A Phase 1/2 study testing tDCS: noninvasive brain stimulation and Constraint induced movement therapy (CIMT) in people with Stroke, run by The Cleveland Clinic at 1 site in United States.
Trial summary
The purpose of this study is to investigate whether benefits of training the affected hand in patients with stroke can be improved by combining training with a painless, noninvasive technique called Transcranial Direct Current Stimulation (TDCS). Read more about this study
- Who is it for?
- Ages 21 years and olderHealthy volunteers can take part
- Conditions the study is for
- Stroke
- What is being tested?
- tDCS: noninvasive brain stimulation and Constraint induced movement therapy (CIMT)
- Type of treatment
- Injection or infusion, Surgery or procedure, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 67 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2011to Dec 2019
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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 21 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Diagnosed with stroke that occurred at least 6 months ago
Who cannot join
- Pregnant
- Ongoing use of Central Nervous System activating medications
- Presence of an electrically, magnetically or mechanically activated implant, including cardiac pacemaker, cochlear implant
- Metal in the head
- A history of medication-resistant epilepsy in the family
- Past history of seizures or unexplained spells of loss of consciousness
Trial locations and contacts
1 site in 1 country.
About this study
The purpose of this study is to investigate whether benefits of training the affected hand in patients with stroke can be improved by combining training with a painless, noninvasive technique called Transcranial Direct Current Stimulation (TDCS). TDCS will be applied over the part of the brain responsible for movements of the affected hand. Also, the investigators will study the changes in the brain that favor recovery of hand function following combination of training and tDCS.
Read the detailed description
The overall goal of this study is to develop a novel rehabilitative method, in chronic stroke, which minimizes residual deficits by maximally utilizing the potential for cortical plasticity.
Despite extensive rehabilitation, approximately 60-80% of patients with stroke experience residual dysfunction of the upper limb. Deficits are believed to linger due to neurophysiologic imbalance between the ipsilesional (stroke-affected) and contralesional (intact) motor cortices. Specifically, the ipsilesional motor cortex loses its normal inhibitory control over the contralesional areas, which, in return, intensify their inhibitory influence upon the former. Constraint-Induced Movement Therapy (CIMT) represents a family of techniques that alleviates residual deficits by rectifying these neurophysiologic imbalances. By reinforcing use of the paretic upper limb in daily life during restraint of the non-paretic limb, CIMT initiates use-dependent neuroplastic reorganization implicating the ipsilesional motor areas, which demonstrate return-of-activity and regain territory in the surviving regions, mitigating the exaggerated inhibitory influence exerted by the contralesional areas.
Despite promising evidence, however, clinical utility of CIMT is limited due to its labor-intensive protocols and inadequate gains. Our objective is to address gaps in existing clinical rehabilitative research. The investigators propose to 1) combine CIMT with targeted stimulation of the ipsilesional motor cortices, 2) Use a novel, noninvasive method of stimulation, called transcranial direct current stimulation (tDCS), 3) Use multimodal imaging to determine comprehensive mechanisms of recovery in patients. Our central hypotheses are 1) ipsilesional motor cortices would be an ideal site for delivering stimulation during CIMT, 2) tDCS will be easy, safe and inexpensive to apply and will target multiple maps concurrently during rehabilitation as demonstrated in our elemental research. 3) structural and functional imaging methods will demonstrate complementary cortical, corticospinal and cortico-muscular markers of recovery.
- Conditions
- Stroke
- Being tested
- tDCS: noninvasive brain stimulation, Constraint induced movement therapy (CIMT), Sham tDCS: placebo noninvasive brain stimulation
- Keywords
- Stroke, Rehabilitation, Paresis, Paralysis, Recovery, tDCS, Transcranial Direct Current Stimulation, CIMT, Constraint Induced Movement Therapy, Stroke therapy, MRI, Hand, CVA, Cerebrovascular accident
- Medical subject headings
- Stroke, Paresis, Paralysis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
tDCS: noninvasive brain stimulationProcedure or surgery
Also called tDCS, noninvasive brain stimulation, neuromodulation, transcranial stimulation
TDCS is a method of noninvasive stimulation of the brain. Using electrodes placed in saline-soaked sponges, low level of direct current (1mA) is delivered over the scalp. This intervention is considered safe and noninvasive because it does not involve implantation or injection or any skin penetration. In the present study, tDCS will be delivered for 1 hr each day for 3 days a week for 5 weeks in conjunction with constraint-induced movement therapy for the affected hand.
Constraint induced movement therapy (CIMT)Behavioural
Also called hand therapy, CIMT, forced use therapy, constraint induced movement therapy
Patients with stroke affecting the hand will receive constraint-induced movement therapy (CIMT) to re-train movements of the affected hand. Training will involve practicing tasks of daily living with qualified personnel. Training will be delivered for 1 hr each day for 3 days a week for 5 weeks. Patients will also be asked to use their affected hand in daily activities at home for 5 hrs a day while wearing a mitt on the unaffected hand.
Sham tDCS: placebo noninvasive brain stimulationProcedure or surgery
Placebo set-up for noninvasive brain stimulation will be similar to that for the active tDCS; sponge electrodes would be placed on the scalp and connected to a batter-operated device. Patients will not receive the effective level of direct current as would delivered in active tDCS intervention. But patients will not be able to decipher whether they are receiving active or placebo tDCS.
| Study group | Role | What they receive |
|---|---|---|
| Sham tDCS plus CIMT | Sham comparator | Subjects in this group will be trained on Constraint induced movement therapy (CIMT) for the hand while concurrently receiving placebo noninvasive brain stimulation (tDCS). They will be receiving Sham tDCS: placebo noninvasive brain stimulation. They will be provided treatment for 3 days a week for 5 weeks for 1 hr each day at the Cleveland Clinic. They would be asked to use affected hand in daily activities for 5 hrs everyday at home while wearing a mitt on their unaffected hand. Receives: Behavioral: Constraint induced movement therapy (CIMT); Procedure: Sham tDCS: placebo noninvasive brain stimulation |
| tDCS plus CIMT | Experimental | Patients with stroke affecting the hand will receive Constraint-induced movement therapy (CIMT) concurrent with tDCS: noninvasive brain stimulation. TDCS will be applied to areas of the brain responsible for movement of the affected hand. This combination of tDCS and CIMT will be delivered for 1 hr each day for 3 days a week for 5 weeks. Patients will also be asked to use their affected hand in daily activities at home for 5 hrs a day while wearing a mitt on the unaffected hand. Receives: Procedure: tDCS: noninvasive brain stimulation; Behavioral: Constraint induced movement therapy (CIMT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Upper limb function following combination of tDCS with CIMT
To address the functional advantage of combining tDCS and CIMT tests that evaluate impairments of the hand will be utilized. Also, change in ability to carry out activities of daily living will be measured.
Measured: Each patient will be given the assessment tests at 3 points during the study, at baseline, interim test (an average of 2.5 weeks from baseline) and at posttest (an average of 5 weeks from baseline).
Secondary outcomes (1)
Study of change in neural mechanisms that underlie the complementary association of cortical stimulation and CIMT
To identify the underlying neural mechanisms in the association of cortical stimulation and CIMT, the patient will undergo structural and functional magnetic resonance imaging (MRI) and tests of neurophysiology.
Measured: Each patient will be given the assessment tests at 3 points during the study, at baseline, interim test (an average of 2.5 weeks from baseline) and at posttest (an average of 5 weeks from baseline)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2012 (estimated)
- Study startJul 2011
- Primary completionDec 2019
- Study completionDec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for StrokeStudies of the same condition, open and under way.
- More trials run by The Cleveland ClinicThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 67 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Cleveland Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Principal investigator, Ela B. Plow, The Cleveland Clinic
- Investigators
- Ela B Plow, PhD PT, Principal investigator, The Cleveland Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01539096
- Sponsor's protocol ID
- 11-586
- Other IDs
- 1K01HD069504-01
- Status last verified
- Jul 2020
- First submitted
- 16 Feb 2012
- Last updated
- 16 Jul 2020
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No: The Investigators will not be sharing or releasing any study data to third parties outside the Cleveland Clinic.
Publications
Unger RH, Lowe MJ, Beall EB, Bethoux F, Jones SE, Machado AG, Plow EB, Cunningham DA. Stimulation of the Premotor Cortex Enhances Interhemispheric Functional Connectivity in Association with Upper Limb Motor Recovery in Moderate-to-Severe Chronic Stroke. Brain Connect. 2023 Oct;13(8):453-463. doi: 10.1089/brain.2022.0064. Epub 2023 Apr 10.
PubMed 36772802Plow EB, Cunningham DA, Beall E, Jones S, Wyant A, Bonnett C, Yue GH, Lowe M, Wang XF, Sakaie K, Machado A. Effectiveness and neural mechanisms associated with tDCS delivered to premotor cortex in stroke rehabilitation: study protocol for a randomized controlled trial. Trials. 2013 Oct 12;14:331. doi: 10.1186/1745-6215-14-331.
PubMed 24119615
Study at a glance
From the registry record, last updated by the sponsor on 16 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Brain Stimulation-aided Stroke Rehabilitation: Neural Mechanisms of Recovery
- ClinicalTrials.gov ID
- NCT01539096
- Acronym / sponsor ID
- 11-586
- Conditions
- Stroke
- Keywords
- Stroke, Rehabilitation, Paresis, Paralysis, Recovery, tDCS, Transcranial Direct Current Stimulation, CIMT
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 67 participants (actual)
- Lead sponsor
- The Cleveland ClinicUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- Jul 2011 (actual)
- Primary completion
- Dec 2019 (actual)
- Study completion
- Dec 2019 (actual)
- First posted
- 27 Feb 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to investigate whether benefits of training the affected hand in patients with stroke can be improved by combining training with a painless, noninvasive technique called Transcranial Direct Current Stimulation (TDCS). TDCS will be applied over the part of the brain responsible for movements of the affected hand. Also, the investigators will study the changes in the brain that favor recovery of hand function following combination of training and tDCS.
Detailed description
The overall goal of this study is to develop a novel rehabilitative method, in chronic stroke, which minimizes residual deficits by maximally utilizing the potential for cortical plasticity.
Despite extensive rehabilitation, approximately 60-80% of patients with stroke experience residual dysfunction of the upper limb. Deficits are believed to linger due to neurophysiologic imbalance between the ipsilesional (stroke-affected) and contralesional (intact) motor cortices. Specifically, the ipsilesional motor cortex loses its normal inhibitory control over the contralesional areas, which, in return, intensify their inhibitory influence upon the former. Constraint-Induced Movement Therapy (CIMT) represents a family of techniques that alleviates residual deficits by rectifying these neurophysiologic imbalances. By reinforcing use of the paretic upper limb in daily life during restraint of the non-paretic limb, CIMT initiates use-dependent neuroplastic reorganization implicating the ipsilesional motor areas, which demonstrate return-of-activity and regain territory in the surviving regions, mitigating the exaggerated inhibitory influence exerted by the contralesional areas.
Despite promising evidence, however, clinical utility of CIMT is limited due to its labor-intensive protocols and inadequate gains. Our objective is to address gaps in existing clinical rehabilitative research. The investigators propose to 1) combine CIMT with targeted stimulation of the ipsilesional motor cortices, 2) Use a novel, noninvasive method of stimulation, called transcranial direct current stimulation (tDCS), 3) Use multimodal imaging to determine comprehensive mechanisms of recovery in patients. Our central hypotheses are 1) ipsilesional motor cortices would be an ideal site for delivering stimulation during CIMT, 2) tDCS will be easy, safe and inexpensive to apply and will target multiple maps concurrently during rehabilitation as demonstrated in our elemental research. 3) structural and functional imaging methods will demonstrate complementary cortical, corticospinal and cortico-muscular markers of recovery.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sham tDCS plus CIMT | Sham comparator | Behavioral: Constraint induced movement therapy (CIMT), Procedure: Sham tDCS: placebo noninvasive brain stimulationSubjects in this group will be trained on Constraint induced movement therapy (CIMT) for the hand while concurrently receiving placebo noninvasive brain stimulation (tDCS). They will be receiving Sham tDCS: placebo noninvasive brain stimulation. They will be provided treatment for 3 days a week for 5 weeks for 1 hr each day at the Cleveland Clinic. They would be asked to use affected hand in daily activities for 5 hrs everyday at home while wearing a mitt on their unaffected hand. |
| tDCS plus CIMT | Experimental | Procedure: tDCS: noninvasive brain stimulation, Behavioral: Constraint induced movement therapy (CIMT)Patients with stroke affecting the hand will receive Constraint-induced movement therapy (CIMT) concurrent with tDCS: noninvasive brain stimulation. TDCS will be applied to areas of the brain responsible for movement of the affected hand. This combination of tDCS and CIMT will be delivered for 1 hr each day for 3 days a week for 5 weeks. Patients will also be asked to use their affected hand in daily activities at home for 5 hrs a day while wearing a mitt on the unaffected hand. |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Diagnosed with stroke that occurred at least 6 months ago
Key exclusion criteria (6 listed)
- Pregnant
- Ongoing use of Central Nervous System activating medications
- Presence of an electrically, magnetically or mechanically activated implant, including cardiac pacemaker, cochlear implant
- Metal in the head
- A history of medication-resistant epilepsy in the family
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 |
|---|---|---|
| tDCS: noninvasive brain stimulationAlso: tDCS, noninvasive brain stimulation, neuromodulation, transcranial stimulationTDCS is a method of noninvasive stimulation of the brain. Using electrodes placed in saline-soaked sponges, low level of direct current (1mA) is delivered over the scalp. This intervention is considered safe and noninvasive because it does not involve implantation or injection or any skin penetration. In the present study, tDCS will be delivered for 1 hr each day for 3 days a week for 5 weeks in conjunction with constraint-induced movement therapy for the affected hand. | Procedure or surgery | tDCS plus CIMT |
| Constraint induced movement therapy (CIMT)Also: hand therapy, CIMT, forced use therapy, constraint induced movement therapyPatients with stroke affecting the hand will receive constraint-induced movement therapy (CIMT) to re-train movements of the affected hand. Training will involve practicing tasks of daily living with qualified personnel. Training will be delivered for 1 hr each day for 3 days a week for 5 weeks. Patients will also be asked to use their affected hand in daily activities at home for 5 hrs a day while wearing a mitt on the unaffected hand. | Behavioural | Sham tDCS plus CIMT, tDCS plus CIMT |
| Sham tDCS: placebo noninvasive brain stimulationPlacebo set-up for noninvasive brain stimulation will be similar to that for the active tDCS; sponge electrodes would be placed on the scalp and connected to a batter-operated device. Patients will not receive the effective level of direct current as would delivered in active tDCS intervention. But patients will not be able to decipher whether they are receiving active or placebo tDCS. | Procedure or surgery | Sham tDCS plus CIMT |
Primary outcome
Change in Upper limb function following combination of tDCS with CIMT
Time frame: Each patient will be given the assessment tests at 3 points during the study, at baseline, interim test (an average of 2.5 weeks from baseline) and at posttest (an average of 5 weeks from baseline).
To address the functional advantage of combining tDCS and CIMT tests that evaluate impairments of the hand will be utilized. Also, change in ability to carry out activities of daily living will be measured.
1 secondary outcome
Study of change in neural mechanisms that underlie the complementary association of cortical stimulation and CIMT
Time frame: Each patient will be given the assessment tests at 3 points during the study, at baseline, interim test (an average of 2.5 weeks from baseline) and at posttest (an average of 5 weeks from baseline)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jul 2020.
- Derived from this study: PubMed 36772802Unger RH, Lowe MJ, Beall EB, Bethoux F, Jones SE, Machado AG, Plow EB, Cunningham DA. Stimulation of the Premotor Cortex Enhances Interhemispheric Functional Connectivity in Association with Upper Limb Motor Recovery in Moderate-to-Severe Chronic Stroke. Brain Connect. 2023 Oct;13(8):453-463. doi: 10.1089/brain.2022.0064. Epub 2023 Apr 10.
- Derived from this study: PubMed 24119615Plow EB, Cunningham DA, Beall E, Jones S, Wyant A, Bonnett C, Yue GH, Lowe M, Wang XF, Sakaie K, Machado A. Effectiveness and neural mechanisms associated with tDCS delivered to premotor cortex in stroke rehabilitation: study protocol for a randomized controlled trial. Trials. 2013 Oct 12;14:331. doi: 10.1186/1745-6215-14-331.
- Individual participant dataSharing planned: No. The Investigators will not be sharing or releasing any study data to third parties outside the Cleveland Clinic.
Related trials for Stroke
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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.
Ela B Plow, PhD PT principal investigator
The Cleveland Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing tDCS: noninvasive brain stimulation and Constraint induced movement therapy (CIMT) in people with Stroke, run by The Cleveland Clinic 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 1 inclusion and 6 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 16 Jul 2020. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Change in Upper limb function following combination of tDCS with CIMT (time frame: Each patient will be given the assessment tests at 3 points during the study, at baseline, interim test (an average of 2.5 weeks from baseline) and at posttest (an average of 5 weeks from baseline).). 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 NCT01539096, which also lists 2 linked publications.
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 16 Jul 2020.