NCT03870672

rTMS Plus CCFES-mediated Functional Task Practice for Severe Stroke

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

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 72 (estimated)
• Sponsor: The Cleveland Clinic · Academic / Other
• Sex: All
• Age: 18 Years – 90 Years
• Healthy volunteers: Not accepted

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 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.

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

Interventions

Type	Name	Description
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.
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.
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.
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.

Timeline

• Start date: 2019-05-14
• Primary completion: 2026-06-30
• Completion: 2026-12-31
• First posted: 2019-03-12
• Last updated: 2026-03-24

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated device study