A Novel Approach for Brain Stimulation in Severe Stroke
- Conditions
- Stroke
- Interventions
- Device: New rTMS ApproachDevice: Conventional rTMS Approach
- Registration Number
- NCT03868410
- Lead Sponsor
- The Cleveland Clinic
- Brief Summary
The long-term goal of this project is to develop upper limb rehabilitation interventions that can be utilized for stroke survivors, specifically survivors with more severe limitations in use of their affected upper limb.
This study will utilize a novel method of non-invasive brain stimulation in conjunction with upper limb training given for 12 visits over a period of 6 weeks.
The study will include the following site visits:
* Eligibility Screening and Informed Consent Visit
* An MRI visit
* Two testing visits in which motor function of the upper limb and neurophysiology will be measured
* 12 intervention visits during which patients will receive upper limb training in conjunction with non-invasive brain stimulation
* Repeat testing of motor function of the upper limb and neurophysiology
* Repeat MRI testing
* A follow-up visit completed 3 months after the completion of interventions
- Detailed Description
In a pilot, randomized clinical trial, 24 stroke patients with moderate/severe impairments will receive non-invasive brain stimulation (repetitive Transcranial Magnetic Stimulation or rTMS) to one of two targets in the brain in conjunction with upper limb training for 2 days a week for 6 weeks. The primary outcome will be upper limb motor impairment, and secondary outcomes will be tests of functional abilities, proximal motor control, and patient-reported disability. Associated neural mechanisms will also be studied using neurophysiological and functional connectivity MRI techniques. Damage to ipsilesional corticospinal pathways will be indexed with diffusion tensor imaging (DTI).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 23
- chronic phase (≥6 months) after index stroke
- moderate or severely impaired (UEFM ≤42)
- have either extensive damage to ipsilesional pathways (MEP-), or, have one of the following: less than 10 degrees active wrist extension, less than 10 degrees active thumb extension/abduction, less than 10 degrees active extension in at least 2 additional digits (i.e. will not meet minimum CMIT criteria).
- medically stable
- cerebellar stroke
- brainstem stroke
- bilateral strokes affecting sensorimotor structures
- severe cognitive impairment
- substantially elevated tone/spasticity in wrist/hand (Modified Ashworth Scale >3)
- severe contracture
- participation in outpatient or Botox therapy within 2 months
- exclusion criteria for TMS and MRI (metal implant in head, H/O seizures, alcohol or substance abuse, intake of medications contraindicated with TMS, cardiac pacemaker or programmable implant).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description cPMD rTMS + Training New rTMS Approach New Approach iM1 rTMS + Training Conventional rTMS Approach Conventional Approach
- Primary Outcome Measures
Name Time Method Change in Upper Extremity Fugyl-Meyer Score (UEFM) through study completion, on average 7 weeks Impairment will be measured using UEFM, one of the most widely used assessments in stroke. UEFM will serve as our primary outcome because it is sensitive to discerning the effects of rTMS/rehabilitation, and has excellent reliability (ICC= 0.97), consistency (Cronbach's α= 0.84) and validity. UEFM has a score ranging from 0-66 (0 meaning there is no movement of the paretic arm, and 66 meaning there is no functional limitation of the paretic arm.)
Change in Inter-hemispheric Inhibition (IHI) through study completion, on average 7 weeks Inter-hemispheric connectivity will be characterized using IHI collected with TMS.
- Secondary Outcome Measures
Name Time Method Change in Stroke Impact Scale (SIS-16) through study completion, on average 7 weeks Patient's perceived disability related to physical function will be indexed using the Stroke Impact Scale (SIS-16) which a subjective questionnaire asked to the subject pertaining of 16 questions. Each question is rated 1-5 and then the scores are totaled. Total scores can range from 16-80 (16 means that none of the functional tasks asked can be performed, a score of 80 means the subject has no issues at all performing any of the tasks asked).
Change Resting State Functional Magnetic Resonance Imaging(rsfMRI) through study completion, on average 7 weeks Functional connectivity will complement IHI measurement as a secondary outcome because while IHI records neurophysiologic interactions between a contralesional and a weak ipsilesional region, functional connectivity defines "global" interactions across multiple regions.
Change in Bimanual Grip Force Modulation Task through study completion, on average 7 weeks Measure the ability to produce and maintain differing levels of force using hand dynamometers. This measurement represents patient's ability to perform independent tasks with each hand.
Change in ipsilateral MEPs (motor evoked potentials) through study completion, on average 7 weeks Output of uncrossed pathways will be studied as ipsilateral MEPs elicited in the paretic-muscle with TMS.
Change in Wolf Motor Function Test (WMFT) through study completion, on average 6 weeks Functional ability to use the paretic upper limb in a variety of tasks will be assessed using WMFT. Time to complete each task will be noted and converted to rate (60/Performance Time (sec)), optimized for measurement in moderately/severely-impaired patients. Grip strength will also be recorded with WMFT.
DTI Baseline DTI enables the investigation of structural integrity and orientation of pathways in vivo through the estimation of magnitude and directionality of water diffusion. DTI metrics can help quantitate damage even when patients show no response to TMS due to extensive damage (MEP-). Ipsilesional and contralesional corticospinal tracts will be reconstructed using probabilistic tractography. FA, a unit-less measure of white matter integrity, will be calculated.
Change in SULCS through study completion, on average 7 weeks is a stroke-specific assessment instrument that evaluates functional capacity of the upper limb based on the execution of 10 tasks.
Trial Locations
- Locations (1)
Lerner Research Institute; Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States