Clinical trial NCT03870672: rTMS Plus CCFES-mediated Functional Task Practice for Severe Stroke
Official title: Contralaterally Controlled FES Combined With Brain Stimulation for Severe Upper Limb Hemiplegia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Stroke
Hemiplegia
Cerebrovascular Accident (CVA)
Hemiparesis
Keywords: Upper limb
Stroke
CVA
Rehabilitation
Brain Stimulation
CCFES
Motor Cortex
TMS
Motor Recovery
Lead sponsor: The Cleveland Clinic
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2019-03-12
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Upper Extremity Fugl-Meyer (UEFM)
timeFrame: Change in UEFM will be assessed at at 6 weeks, 12 weeks (end of treatment), 24 weeks, and 36 weeks.
Secondary outcomes:
Other outcomes:
measure: Change in Neurophysiologic Assessments
timeFrame: 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.
Locations:
city: Cleveland
country: United States
facility: Lerner Research Institute; Cleveland Clinic Foundation
state: Ohio
Study officials:
affiliation: Lerner Research Institute; Cleveland Clinic Foundation
name: Ela B Plow, PhD PT
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.