StrokerTMS+CCFESNCT03870672
rTMS Plus CCFES-mediated Functional Task Practice for Severe Stroke
A study testing New rTMS approach and Conventional rTMS approach in people with Stroke and Hemiplegia, run by The Cleveland Clinic at 1 site in United States.
Trial summary
This study is a necessary and important step in the development of a new therapy for upper limb functional recovery in patients with severe motor impairment. It is the first clinical trial of non-invasive brain stimulation (repetitive transcranial magnetic stimulation or rTMS) delivered to excite the undamaged… Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Stroke, Hemiplegia, Cerebrovascular Accident (CVA)
- What is being tested?
- New rTMS approach and Conventional rTMS approach
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 72 participants
- Where
- 1 siteUnited States
- Study dates
- 14 May 2019to 31 Dec 2026
- Phase
- Interventional
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 to 90 years old at time of randomization
- greater than 6 months since a first clinical cortical or subcortical, ischemic or hemorrhagic stroke
- severe upper limb hemiparesis defined as less than 10° active wrist extension or less than 10° active thumb abduction/extension or less than 10° active extension in at least two additional digits (i.e., will not meet minimum CIMT criteria)
- ability to follow 3-stage commands and can remember 2 items from a list of 3 items after 3 minutes
- adequate active movement of shoulder and elbow to position the paretic hand on one's lap for performance of functional task practice and CCFES-assisted hand opening exercises
- skin intact on hemiparetic arm
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- surface electrical stimulation of the paretic finger and thumb extensors produces functional hand opening without pain
- able to hear and respond to cues from stimulator
- completed occupational therapy at least 2 months prior to enrollment (no concomitant OT)
- full volitional hand opening/closing of the non-paretic hand
- ability to follow instructions for putting on and operating the CCFES stimulator or a caregiver available to provide assistance
Who cannot join
- metal implant in the head
- history of seizures as an adult
- history of alcohol or substance abuse less than 10yrs prior to enrollment
- intake of anticonvulsants or anti-depressants contraindicated with TMS
- cardiac pacemaker or other programmable implant
Trial locations and contacts
1 site in 1 country.
United States1 site
Lerner Research Institute; Cleveland Clinic Foundation
Cleveland, Ohio, 44195
About this study
Official title: Contralaterally Controlled FES Combined With Brain Stimulation for Severe Upper Limb Hemiplegia
This study is a necessary and important step in the development of a new therapy for upper limb functional recovery in patients with severe motor impairment. It is the first clinical trial of non-invasive brain stimulation (repetitive transcranial magnetic stimulation or rTMS) delivered to excite the undamaged hemisphere (specifically the contralesional higher motor cortices or cHMC) in stroke. Therefore, this study will determine whether the positive results obtained in our short-term pilot study can be made to last longer and produce functional benefits in severe patients with the application of brain stimulation in combination with long-term rehabilitation therapy. Rehabilitation therapy administered is called contralaterally controlled functional electrical stimulation (CCFES). Determining whether combining rTMS facilitating the cHMC with CCFES produces synergistic gains in functional abilities in severe patients is necessary for acceptance by the clinical community and to move this technology toward commercialization and widespread dissemination. The proposed study will determine whether the combination of rTMS facilitating the cHMC with CCFES produces greater improvements in upper extremity function in severe participants who are ≥6 months from stroke onset than the combination of rTMS facilitating the damaged hemisphere (specifically the ipsilesional primary motor cortex, iM1) and CCFES or the combination of sham rTMS and CCFES. The secondary purposes are to define which patients benefit most from the treatments, which may inform future device and treatment development and clinical translation, and to explore what distinct effects the three treatments have on the brain. To accomplish these purposes, we are conducting a clinical trial that enrolls severe stroke patients.
Read the detailed description
Overall Study Design Summary: We propose a 5-yr RCT in which 72 stroke patients who are >6 months post-stroke are randomized to 12 wks of one of 3 treatments: (1) CCFES + cHMC facilitation, (2) CCFES + iM1 facilitation, (3) CCFES + Sham rTMS. The treatment dose will be the same for all groups: 10 sessions per week (7.5 hrs) of self-administered CCFES-assisted hand opening exercises performed at home plus 2 sessions per week (2.5 hrs) consisting of group-specific rTMS and CCFES-mediated functional task practice performed in the laboratory. Upper limb impairment, activity limitation, and patient-reported disability will be assessed at 0 (baseline), 6, 12 (end of treatment), 24, and 36 wks. Neurophysiology (IHI and excitability of uncrossed output) will be assessed at 0 (baseline), 12 (end of treatment), and 36 wks, on a separate day from functional motor outcomes assessment. MRI assessment of stroke lesion and location, and DTI assessment of corticospinal damage will be performed at baseline.
- Conditions
- Stroke, Hemiplegia, Cerebrovascular Accident (CVA), Hemiparesis
- Being tested
- Contralaterally Controlled Functional Electrical Stimulation, New rTMS approach, Conventional rTMS approach, Sham rTMS approach
- Keywords
- Upper limb, Stroke, CVA, Rehabilitation, Brain Stimulation, CCFES, Motor Cortex, TMS, Motor Recovery
- Medical subject headings
- Stroke, Hemiplegia, Paresis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Contralaterally Controlled Functional Electrical StimulationDevice
Also called CCFES
Contralaterally Controlled Functional Electrical Stimulation (CCFES) uses electrical stimulation to open the weak hand. Sticky patches called electrodes are placed on the participant's affected arm to stimulate the hand muscles, and a special glove is worn on the participant's strong hand and controls the stimulator. When the participant opens the gloved hand, stimulation opens the weak hand; when they close the gloved hand, stimulation turns off and the weak hand relaxes. During the clinic visits, participants will use CCFES to assist hand opening during functional training. During participant home sessions, they will use CCFES to perform hand opening exercise.
New rTMS approachDevice
Also called cHMC rTMS + CCFES and upper limb training
Participants in this arm will receive rTMS-based facilitation of the contralesional dorsal premotor cortex (cPMd) located in the non-stroke hemisphere before start of each session. High-frequency rTMS (5-Hz) will be delivered using 42 10-sec trains of 50 pulses each (total 2100 pulses) for a period of 24 minutes. Immediately after the completion of rTMS, participants will undergo upper limb training + CCFES for a total of one hour. Participants will receive these interventions 2 days a week for 12 weeks.
Conventional rTMS approachDevice
Also called iM1 rTMS + CCFES and upper limb training
Facilitation of M1 will be achieved using 5Hz rTMS. High-frequency rTMS (5-Hz) will be delivered using 42 10-sec trains of 50 pulses each (total 2100 pulses) for a period of 24 minutes. Immediately after the completion of rTMS, participants will undergo upper limb training + CCFES for a total of one hour. Participants will receive these interventions 2 days a week for 12 weeks.
Sham rTMS approachDevice
Also called Sham rTMS + CCFES and upper limb training
In the sham rTMS group, ipsilesional motor hotspot will be targeted in half the patients and cHMC location will be targeted in the other half (based on random assignment). Immediately after the completion of rTMS, participants will undergo upper limb training + CCFES for a total of one hour. Participants will receive these interventions 2 days a week for 12 weeks.
| Study group | Role | What they receive |
|---|---|---|
| CCFES + rTMS facilitating cHMC | Active comparator | This rTMS paradigm is the "New Approach". Facilitation of the intact hemisphere target (cHMC) will be achieved using 5Hz rTMS. After rTMS, the participant will participate in one hour of CCFES-mediated functional task practice. The therapist will instruct and guide the participants in practicing functional tasks with their paretic hand with the assistance of CCFES. Tasks will involve using the paretic hand to pick up, manipulate, and release objects commonly used in daily life. Early sessions will focus on simpler tasks, such as practicing opening the hand adequately to acquire an object. Receives: Device: Contralaterally Controlled Functional Electrical Stimulation; Device: New rTMS approach |
| CCFES + rTMS facilitating iM1 | Active comparator | This rTMS paradigm is the "Conventional Approach".Facilitation of M1 will be achieved using 5Hz rTMS. After rTMS, the participant will participate in one hour of CCFES-mediated functional task practice. The therapist will instruct and guide the participants in practicing functional tasks with their paretic hand with the assistance of CCFES. Tasks will involve using the paretic hand to pick up, manipulate, and release objects commonly used in daily life. Early sessions will focus on simpler tasks, such as practicing opening the hand adequately to acquire an object. Receives: Device: Contralaterally Controlled Functional Electrical Stimulation; Device: Conventional rTMS approach |
| CCFES + Sham rTMS | Sham comparator | This rTMS paradigm is the "Sham Approach". Immediately after sham rTMS, the participant will participate in one hour of CCFES-mediated functional task practice. The therapist will instruct and guide the participants in practicing functional tasks with their paretic hand with the assistance of CCFES. Tasks will involve using the paretic hand to pick up, manipulate, and release objects commonly used in daily life. Early sessions will focus on simpler tasks, such as practicing opening the hand adequately to acquire an object. Receives: Device: Contralaterally Controlled Functional Electrical Stimulation; Device: Sham rTMS approach |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Upper Extremity Fugl-Meyer (UEFM)
The UEFM is a reliable and valid measure of post-stroke upper limb motor impairment. The UEFM items take into account synergy patterns, isolated strength, coordination, and hypertonia. Volitional movement of the upper limb (shoulder, elbow, forearm, wrist, and hand) is examined in and out of synergies. Each item is graded on a 3-point ordinal scale (0, cannot perform; 1, perform partially; and 2, perform fully) and summed to provide a maximum score of 66. The UEFM is classified as a body structure/function impairment measure on the ICF domain.
Measured: Change in UEFM will be assessed at at 6 weeks, 12 weeks (end of treatment), 24 weeks, and 36 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2019
- Study start14 May 2019
- Primary completion23 Jul 2026
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- In a randomized-controlled, assessor-blinded clinical trial, an anticipated 72 patients will be assigned to receive 12 weeks of CCFES + cHMC facilitation, or CCFES + iM1 facilitation, or CCFES + sham rTMS. Assessments of upper limb motor function and neurophysiology will be completed at baseline, 6, 12, 24, and 36 weeks. This study will 1) determine whether cHMC facilitation augments the effects of CCFES to produce greater improvements in upper limb function in severe patients, 2) investigate the underlying neurophysiologic mechanisms contributing to restored paretic limb motor control, and 3) evaluate and identify patient factors that affect efficacy of CCFES + cHMC facilitation.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 72 participants (estimated)
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, Lerner Research Institute; Cleveland Clinic Foundation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03870672
- Sponsor's protocol ID
- 19-286
- Other IDs
- R01HD098073
- Acronym
- rTMS+CCFES
- Status last verified
- Aug 2026
- First submitted
- 6 Mar 2019
- Last updated
- 26 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Mohan A, Knutson JS, Cunningham DA, Widina M, O'Laughlin K, Arora T, Li X, Sakaie K, Wang X, Uchino K, Plow EB. Contralaterally Controlled Functional Electrical Stimulation Combined With Brain Stimulation for Severe Upper Limb Hemiplegia-Study Protocol for a Randomized Controlled Trial. Front Neurol. 2022 Apr 29;13:869733. doi: 10.3389/fneur.2022.869733. eCollection 2022.
PubMed 35599736