rTMS Plus CCFES-mediated Functional Task Practice for Severe Stroke (rTMS+CCFES)

August 25, 2026 updated by: Ela B. Plow, The Cleveland Clinic

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
72

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Ela B. Plow, PhD PT
  • Phone Number: 216-445-4589
  • Email: plowe2@ccf.oeg

Study Contact Backup

  • Name: Kyle J. O'Laughlin, MS
  • Phone Number: 866-449-1394
  • Email: olaughk@ccf.org

Study Locations

  • United States
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Lerner Research Institute; Cleveland Clinic Foundation

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 90 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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
  • 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

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: CCFES + rTMS facilitating cHMC
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.
Device: Contralaterally Controlled Functional Electrical Stimulation
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.
Other Names:
  • CCFES
Device: New rTMS approach
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.
Other Names:
  • cHMC rTMS + CCFES and upper limb training
Active Comparator: CCFES + rTMS facilitating iM1
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.
Device: Contralaterally Controlled Functional Electrical Stimulation
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.
Other Names:
  • CCFES
Device: Conventional rTMS approach
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.
Other Names:
  • iM1 rTMS + CCFES and upper limb training
Sham Comparator: CCFES + Sham rTMS
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.
Device: Contralaterally Controlled Functional Electrical Stimulation
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.
Other Names:
  • CCFES
Device: Sham rTMS approach
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.
Other Names:
  • Sham rTMS + CCFES and upper limb training

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in Upper Extremity Fugl-Meyer (UEFM)
Time Frame: Change in UEFM will be assessed at at 6 weeks, 12 weeks (end of treatment), 24 weeks, and 36 weeks.
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.
Change in UEFM will be assessed at at 6 weeks, 12 weeks (end of treatment), 24 weeks, and 36 weeks.

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in Neurophysiologic Assessments
Time Frame: Change in neurophysiologic indices will be measured at 12 weeks (end of treatment) and at 36 weeks, on a separate day from functional motor outcomes assessment.
Neurophysiologic assessments will be performed using TMS. While patients are seated with forearms resting and supported on a flat surface, a 70mm figure-of-eight coil will be positioned over the scalp at locations corresponding to motor hotspots. Coil placement and targeting will be guided using MRI-stereotaxy, same as with rTMS. Surface EMG electrodes will be attached to paretic and non-paretic EDC (and other muscles, as explained below) to record MEPs and changes in ongoing muscle activity. Inter-hemispheric interactions and excitability of pathways devoted to weak muscles will help characterize role of the intact, contralesional motor cortices.
Change in neurophysiologic indices will be measured at 12 weeks (end of treatment) and at 36 weeks, on a separate day from functional motor outcomes assessment.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
The Cleveland Clinic

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Ela B Plow, PhD PT, Lerner Research Institute; Cleveland Clinic Foundation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 14, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 23, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 6, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 8, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 12, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 26, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 25, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 19-286
  • R01HD098073 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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