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

NeuroTherapia, Inc.

Status: Enrolling

Conditions: Stroke; Cerebrovascular Accident (CVA); Hemiparesis; Hemiplegia

Treatments: Device: Sham rTMS approach; Device: Contralaterally Controlled Functional Electrical Stimulation; Device: Conventional rTMS approach; Device: New rTMS approach

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT03870672

19-286

R01HD098073 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 72 estimated patients

Sex: All

Ages: 18 to 90 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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72 participants in 3 patient groups

CCFES + rTMS facilitating cHMC

Active Comparator group

Description:

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.

Treatment:

Device: New rTMS approach

Device: Contralaterally Controlled Functional Electrical Stimulation

CCFES + rTMS facilitating iM1

Active Comparator group

Description:

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.

Treatment:

Device: Conventional rTMS approach

Device: Contralaterally Controlled Functional Electrical Stimulation

CCFES + Sham rTMS

Sham Comparator group

Description:

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.

Treatment:

Device: Contralaterally Controlled Functional Electrical Stimulation

Device: Sham rTMS approach