StrokeEarly Phase 1NCT05381740
A Novel Brain Stimulation for Bimanual Motor Function and Control in Chronic Stroke
A Early Phase 1 study testing Novel rTMS Approach in people with Stroke, run by The Cleveland Clinic at 1 site in United States.
Trial summary
The long-term goal of this project is to develop and test upper Iimb rehabilitation interventions that can improve bimanual motor function, or the ability to use both arms and hands together, for stroke survivors with moderate to severe impairment. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Stroke
- What is being tested?
- Novel rTMS Approach
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Mar 2022to 1 Jan 2024
- Phase
- Early Phase 1
- 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 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18-90 yrs
- ≥6 months since first clinical stroke
- Impairment of the paretic hand, indicated by a score of <= 11 out of 14 on the hand section of UEFM
- Sufficient range of motion in the wrist and fingers for functional task practice: have at least 10 degrees active wrist extension, 10 degrees active thumb abduction/extension, and 10 degrees active extension in at least 2 additional digits
- Sufficient active shoulder and elbow movement to volitionally position the paretic hand in the workspace for table-top task practice
Who cannot join
- Brainstem or cerebellar stroke
- Bilateral strokes or multiple strokes affecting sensorimotor structures
- Cognitive impairment (Mini-Mental State Examination <24)
- Severe impairment of the paretic hand that limits functional task practice (UEFM hand score < 4 out of 14)
- Severe spasticity (Modified Ashworth Scale >3) or upper limb contracture
- Occupational therapy or upper limb Botox completed ≤ 2 months prior
- Contraindications to TMS or MRI (e.g. metal implant in head, seizure history, cardiac pacemaker)
Trial locations and contacts
1 site in 1 country.
United States1 site
Lerner Research Institute, Cleveland Clinic Foundation
Cleveland, Ohio, 44195
About this study
The long-term goal of this project is to develop and test upper Iimb rehabilitation interventions that can improve bimanual motor function, or the ability to use both arms and hands together, for stroke survivors with moderate to severe impairment.
This study will utilize a novel method of non-invasive brain stimulation in conjunction with upper limb training given for 12 visits over a period of 6 weeks.
Read more
The study will include the following site visits:
- Eligibility Screening and Informed Consent Visit
- Baseline testing (4 visits total): 1 visit each for MRI, upper limb and bimanual motor function test, bimanual motor control, and neurophysiology related to control of the upper limbs
- Repeat baseline testing (4 visits total) of MRI, upper limb and bimanual motor function test, bimanual motor control, and neurophysiology related to control of the upper limbs
- 12 intervention visits during which patients will receive upper limb therapy in conjunction with non-invasive brain stimulation
- Repeat testing (4 visits total) of MRI, upper limb and bimanual motor function test, bimanual motor control, and neurophysiology related to control of the upper limbs
- A follow-up visit 1 month after the completion of interventions
Read the detailed description
In a pilot randomized controlled clinical trial, 18 stroke survivors more than 6 months after stroke onset, and have upper limb impairment will be enrolled. Participants will be randomized to receive a form of non-invasive brain stimulation called repetitive transcranial magnetic stimulation or rTMS or sham rTMS. Real or sham rTMS will be delivered over an area in the brain called the higher motor cortices within the stroke-unaffected hemisphere, cHMC for short. This area (cHMC) is important for using both arms and hands together, or bimanual motor function. Real or sham cHMC rTMS will be given prior to upper limb therapy twice a week for 6 weeks in the lab. The investigators will measure bimanual motor function and control twice at the beginning, once after the 6-week treatment and once at 1-month after treatment. The investigators will also test possible mechanisms related to the treatment using brain functional MRI and TMS twice at the beginning and once after 6-week treatment.
- Conditions
- Stroke
- Being tested
- Novel rTMS Approach, Sham rTMS Approach
- Keywords
- stroke, brain stimulation, TMS, Upper Limb, rehabilitation, MRI, CVA, neuromodulation
- Medical subject headings
- Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Novel rTMS ApproachDevice
Participants in this arm will receive rTMS-based facilitation of the contralesional higher motor cortices located in the non-stroke hemisphere before the start of each rehabilitation session. High-frequency rTMS (5Hz) will be delivered using 42 10 second trains of 50 pulses each (total 2100 pulses) for a period of 22 minutes. Immediately after the completion of rTMS, participants will undergo therapist-guided upper limb therapy for a total of one hour. Participants will receive these interventions 2 days a week for 6 weeks for a total of 12 sessions.
Sham rTMS ApproachDevice
Participants in this arm will receive sham rTMS given over the contralesional higher motor cortices located in the non-stroke hemisphere before the start of each rehabilitation session. Immediately after the completion of sham rTMS, participants will undergo therapist-guided upper limb therapy for a total of one hour. Participants will receive these interventions 2 days a week for 6 weeks for a total of 12 sessions.
| Study group | Role | What they receive |
|---|---|---|
| cHMC rTMS + Upper Limb Training Training | Experimental | Real Repetitive Transcranial Magnetic Stimulation given to facilitate the Contralesional Higher Motor Cortices+ Upper Limb Training Receives: Device: Novel rTMS Approach |
| Sham rTMS + Upper Limb Training Training | Sham comparator | Sham Repetitive Transcranial Magnetic Stimulation over Contralesional Higher Motor Cortices+ Upper Limb Training Receives: Device: Sham rTMS Approach |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Bimanual Assessment Measure (BAM)
Measure of the functional ability to perform 11 bimanual tasks scoring the spontaneous role of the affected hand, timing, and quality of movement.
Measured: Baseline (0 weeks and 2 weeks), after intervention(up to 7 weeks) and after end of 1 month of follow-up.
Secondary outcomes (6)
Change in Bimanual Grip Force Modulation Task
Measure the ability to produce and maintain differing levels of force using hand dynamometers. This measurement represents patient's ability to perform independent tasks with each hand.
Measured: Baseline (0 weeks and 2 weeks), after intervention(up to 7 weeks) and after end of 1 month of follow-up.
Change in ABILHAND
ABILHAND assesses the participant's perception of bimanual ability by rating the difficulty of performing 23 bimanual activities without assistance on a 3 point ordinal scale (impossible, difficult, easy) This test has excellent reliability (ICC = 0.85-0.91).
Measured: Baseline (0 weeks and 2 weeks), after intervention(up to 7 weeks) and after end of 1 month of follow-up.
Change in Upper Extremity Fugyl-Meyer Score (UEFM)
Impairment will be measured using UEFM, one of the most widely used assessments in stroke. UEFM will serve as our primary outcome because it is sensitive to discerning the effects of rTMS/rehabilitation, and has excellent reliability (ICC= 0.97), consistency (Cronbach's α= 0.84) and validity. UEFM has a score ranging from 0-66 (0 meaning there is no movement of the paretic arm, and 66 meaning there is no functional limitation of the paretic arm.)
Measured: Baseline (0 weeks and 2 weeks), after intervention(up to 7 weeks) and after end of 1 month of follow-up.
Change in Wolf Motor Function Test (WMFT)
Functional ability to use the paretic upper limb in a variety of tasks will be assessed using WMFT. Time to complete each task will be noted and converted to rate (60/Performance Time (sec)), optimized for measurement in moderately/severely-impaired patients. Grip strength will also be recorded with WMFT.
Measured: Baseline (0 weeks and 2 weeks), after intervention(up to 7 weeks) and after end of 1 month of follow-up.
Change Resting State Functional Magnetic Resonance Imaging(rsfMRI)
Functional connectivity will assess the connectivity between cHMC and iM1 using temporal correlation of blood oxygneation level-dependent (BOLD) signal given as z-scores.
Measured: Baseline (0 weeks and 2 weeks), after intervention(up to 7 weeks)
Change in excitability of cortical and corticospinal physiology (TMS)
Transcranial magnetic stimulation will be used to test crossed and uncrossed output from both hemispheres and will be measured as motor evoked potentials(MEPS) of the Extensor Digitorum Communis (EDC).
Measured: Baseline (0 weeks and 2 weeks), after intervention(up to 7 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 May 2022
- Study start8 Mar 2022
- Primary completion6 Dec 2023
- Study completion1 Jan 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- In a prospective randomized controlled trial, an anticipated 18 stroke survivors with chronic (≥6 months) upper limb impairment will receive real or sham stimulation to the non-stroke hemisphere (cHMC). Stimulation will be delivered in conjunction with upper limb rehabilitation for 2 days a week for 6 weeks.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Cleveland Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- American Heart Association
- Responsible party
- Principal investigator, Ela B. Plow, The Cleveland Clinic
- Investigators
- Ela Plow, PhD, Principal investigator, The Cleveland Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05381740
- Sponsor's protocol ID
- 22-074
- Status last verified
- May 2024
- First submitted
- 16 May 2022
- Last updated
- 3 Jun 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Haaland KY, Mutha PK, Rinehart JK, Daniels M, Cushnyr B, Adair JC. Relationship between arm usage and instrumental activities of daily living after unilateral stroke. Arch Phys Med Rehabil. 2012 Nov;93(11):1957-62. doi: 10.1016/j.apmr.2012.05.011. Epub 2012 May 24.
PubMed 22634230Sankarasubramanian V, Machado AG, Conforto AB, Potter-Baker KA, Cunningham DA, Varnerin NM, Wang X, Sakaie K, Plow EB. Inhibition versus facilitation of contralesional motor cortices in stroke: Deriving a model to tailor brain stimulation. Clin Neurophysiol. 2017 Jun;128(6):892-902. doi: 10.1016/j.clinph.2017.03.030. Epub 2017 Mar 21.
PubMed 28402865Liao WW, Whitall J, Wittenberg GF, Barton JE, McCombe Waller S. Not all brain regions are created equal for improving bimanual coordination in individuals with chronic stroke. Clin Neurophysiol. 2019 Aug;130(8):1218-1230. doi: 10.1016/j.clinph.2019.04.711. Epub 2019 May 13.
PubMed 31163366
Study at a glance
From the registry record, last updated by the sponsor on 3 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Novel Brain Stimulation for Bimanual Motor Function and Control in Chronic Stroke
- ClinicalTrials.gov ID
- NCT05381740
- Acronym / sponsor ID
- 22-074
- Conditions
- Stroke
- Keywords
- stroke, brain stimulation, TMS, Upper Limb, rehabilitation, MRI, CVA, neuromodulation
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- The Cleveland ClinicUniversity, hospital or other
- Collaborators
- American Heart Association
- Study start
- 8 Mar 2022 (actual)
- Primary completion
- 6 Dec 2023 (actual)
- Study completion
- 1 Jan 2024 (actual)
- First posted
- 19 May 2022 (actual)
- 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 long-term goal of this project is to develop and test upper Iimb rehabilitation interventions that can improve bimanual motor function, or the ability to use both arms and hands together, for stroke survivors with moderate to severe impairment.
This study will utilize a novel method of non-invasive brain stimulation in conjunction with upper limb training given for 12 visits over a period of 6 weeks.
The study will include the following site visits:
- Eligibility Screening and Informed Consent Visit
- Baseline testing (4 visits total): 1 visit each for MRI, upper limb and bimanual motor function test, bimanual motor control, and neurophysiology related to control of the upper limbs
- Repeat baseline testing (4 visits total) of MRI, upper limb and bimanual motor function test, bimanual motor control, and neurophysiology related to control of the upper limbs
- 12 intervention visits during which patients will receive upper limb therapy in conjunction with non-invasive brain stimulation
- Repeat testing (4 visits total) of MRI, upper limb and bimanual motor function test, bimanual motor control, and neurophysiology related to control of the upper limbs
- A follow-up visit 1 month after the completion of interventions
Detailed description
In a pilot randomized controlled clinical trial, 18 stroke survivors more than 6 months after stroke onset, and have upper limb impairment will be enrolled. Participants will be randomized to receive a form of non-invasive brain stimulation called repetitive transcranial magnetic stimulation or rTMS or sham rTMS. Real or sham rTMS will be delivered over an area in the brain called the higher motor cortices within the stroke-unaffected hemisphere, cHMC for short. This area (cHMC) is important for using both arms and hands together, or bimanual motor function. Real or sham cHMC rTMS will be given prior to upper limb therapy twice a week for 6 weeks in the lab. The investigators will measure bimanual motor function and control twice at the beginning, once after the 6-week treatment and once at 1-month after treatment. The investigators will also test possible mechanisms related to the treatment using brain functional MRI and TMS twice at the beginning and once after 6-week treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- In a prospective randomized controlled trial, an anticipated 18 stroke survivors with chronic (≥6 months) upper limb impairment will receive real or sham stimulation to the non-stroke hemisphere (cHMC). Stimulation will be delivered in conjunction with upper limb rehabilitation for 2 days a week for 6 weeks.
| Arm | Type | Receives |
|---|---|---|
| cHMC rTMS + Upper Limb Training Training | Experimental | Device: Novel rTMS ApproachReal Repetitive Transcranial Magnetic Stimulation given to facilitate the Contralesional Higher Motor Cortices+ Upper Limb Training |
| Sham rTMS + Upper Limb Training Training | Sham comparator | Device: Sham rTMS ApproachSham Repetitive Transcranial Magnetic Stimulation over Contralesional Higher Motor Cortices+ Upper Limb Training |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age 18-90 yrs
- ≥6 months since first clinical stroke
- Impairment of the paretic hand, indicated by a score of <= 11 out of 14 on the hand section of UEFM
- Sufficient range of motion in the wrist and fingers for functional task practice: have at least 10 degrees active wrist extension, 10 degrees active thumb abduction/extension, and 10 degrees active extension in at least 2 additional digits
- Sufficient active shoulder and elbow movement to volitionally position the paretic hand in the workspace for table-top task practice
Key exclusion criteria (7 listed)
- Brainstem or cerebellar stroke
- Bilateral strokes or multiple strokes affecting sensorimotor structures
- Cognitive impairment (Mini-Mental State Examination <24)
- Severe impairment of the paretic hand that limits functional task practice (UEFM hand score < 4 out of 14)
- Severe spasticity (Modified Ashworth Scale >3) or upper limb contracture
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 |
|---|---|---|
| Novel rTMS ApproachParticipants in this arm will receive rTMS-based facilitation of the contralesional higher motor cortices located in the non-stroke hemisphere before the start of each rehabilitation session. High-frequency rTMS (5Hz) will be delivered using 42 10 second trains of 50 pulses each (total 2100 pulses) for a period of 22 minutes. Immediately after the completion of rTMS, participants will undergo therapist-guided upper limb therapy for a total of one hour. Participants will receive these interventions 2 days a week for 6 weeks for a total of 12 sessions. | Device | cHMC rTMS + Upper Limb Training Training |
| Sham rTMS ApproachParticipants in this arm will receive sham rTMS given over the contralesional higher motor cortices located in the non-stroke hemisphere before the start of each rehabilitation session. Immediately after the completion of sham rTMS, participants will undergo therapist-guided upper limb therapy for a total of one hour. Participants will receive these interventions 2 days a week for 6 weeks for a total of 12 sessions. | Device | Sham rTMS + Upper Limb Training Training |
Primary outcome
Change in Bimanual Assessment Measure (BAM)
Time frame: Baseline (0 weeks and 2 weeks), after intervention(up to 7 weeks) and after end of 1 month of follow-up.
Measure of the functional ability to perform 11 bimanual tasks scoring the spontaneous role of the affected hand, timing, and quality of movement.
6 secondary outcomes
Change in Bimanual Grip Force Modulation Task
Time frame: Baseline (0 weeks and 2 weeks), after intervention(up to 7 weeks) and after end of 1 month of follow-up.
Change in ABILHAND
Time frame: Baseline (0 weeks and 2 weeks), after intervention(up to 7 weeks) and after end of 1 month of follow-up.
Change in Upper Extremity Fugyl-Meyer Score (UEFM)
Time frame: Baseline (0 weeks and 2 weeks), after intervention(up to 7 weeks) and after end of 1 month of follow-up.
Change in Wolf Motor Function Test (WMFT)
Time frame: Baseline (0 weeks and 2 weeks), after intervention(up to 7 weeks) and after end of 1 month of follow-up.
Change Resting State Functional Magnetic Resonance Imaging(rsfMRI)
Time frame: Baseline (0 weeks and 2 weeks), after intervention(up to 7 weeks)
Change in excitability of cortical and corticospinal physiology (TMS)
Time frame: Baseline (0 weeks and 2 weeks), after intervention(up to 7 weeks)
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 3 Jun 2024.
- Background: PubMed 22634230Haaland KY, Mutha PK, Rinehart JK, Daniels M, Cushnyr B, Adair JC. Relationship between arm usage and instrumental activities of daily living after unilateral stroke. Arch Phys Med Rehabil. 2012 Nov;93(11):1957-62. doi: 10.1016/j.apmr.2012.05.011. Epub 2012 May 24.
- Background: PubMed 28402865Sankarasubramanian V, Machado AG, Conforto AB, Potter-Baker KA, Cunningham DA, Varnerin NM, Wang X, Sakaie K, Plow EB. Inhibition versus facilitation of contralesional motor cortices in stroke: Deriving a model to tailor brain stimulation. Clin Neurophysiol. 2017 Jun;128(6):892-902. doi: 10.1016/j.clinph.2017.03.030. Epub 2017 Mar 21.
- Background: PubMed 31163366Liao WW, Whitall J, Wittenberg GF, Barton JE, McCombe Waller S. Not all brain regions are created equal for improving bimanual coordination in individuals with chronic stroke. Clin Neurophysiol. 2019 Aug;130(8):1218-1230. doi: 10.1016/j.clinph.2019.04.711. Epub 2019 May 13.
- Individual participant dataSharing planned: No
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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 Plow, PhD 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 Early Phase 1 study testing Novel rTMS Approach 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 5 inclusion and 7 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 3 Jun 2024. 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 phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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 Bimanual Assessment Measure (BAM) (time frame: Baseline (0 weeks and 2 weeks), after intervention(up to 7 weeks) and after end of 1 month of follow-up.). 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 NCT05381740, which also lists 3 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 3 Jun 2024.