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NCT Number: NCT03870672

rTMS Plus CCFES-mediated Functional Task Practice for Severe Stroke

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.

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Key information

Conditions

Stroke Brain Diseases Cardiovascular Diseases Central Nervous System Diseases Cerebrovascular Accident (CVA) Cerebrovascular Disorders Hemiparesis Hemiplegia Nervous System Diseases Neurologic Manifestations Paralysis Paresis Pathological Conditions, Signs and Symptoms Signs and Symptoms Vascular Diseases

Age range

18 year–90 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Contralaterally Controlled Functional Electrical Stimulation

Device

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

New rTMS approach

Device

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

Conventional rTMS approach

Device

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 rTMS approach

Device

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

Primary outcomes

  1. 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.

Other outcomes

  1. 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.

Study contacts

Contact information is provided by the study sponsor or research team.

Ela B. Plow, PhD PT

CONTACT

[email protected]

216-445-4589

Kyle J. O'Laughlin, MS

CONTACT

[email protected]

866-449-1394

Sponsors and collaborators

Lead sponsor

The Cleveland Clinic

Other

Collaborators

  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Registry information

Official study title

Contralaterally Controlled FES Combined With Brain Stimulation for Severe Upper Limb Hemiplegia

Acronym: rTMS+CCFES

Important dates

Study start
2019
Primary completion
2026
Study completion
2026
First posted
Mar 12, 2019
Registry last updated
Mar 24, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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