A Novel Approach for Brain Stimulation in Severe Stroke
Overview
- Phase
- Early Phase 1
- Intervention
- Not specified
- Conditions
- Stroke
- Sponsor
- The Cleveland Clinic
- Enrollment
- 16
- Locations
- 1
- Primary Endpoint
- Change in Upper Extremity Fugyl-Meyer Score (UEFM)
- Status
- Completed
- Last Updated
- 11 months ago
Overview
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).
Investigators
Ela B. Plow
Assistant Staff
The Cleveland Clinic
Eligibility Criteria
Inclusion Criteria
- •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 Constraint-Induced Movement Therapy \[CIMT\] criteria).
- •medically stable
Exclusion Criteria
- •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).
Outcomes
Primary Outcomes
Change in Upper Extremity Fugyl-Meyer Score (UEFM)
Time Frame: Change between Baseline and Post-Test (average 6 weeks)
Change between Baseline and Post-Test (average 6 weeks) is reported for the UEFM. 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)
Time Frame: Change between Baseline and Post-Test (average 6 weeks)
Inter-hemispheric connectivity (IHI) will be collected with transcranial magnetic stimulation (TMS) and is assessed using ipsilateral silent period (ISP) method. TMS is delivered to the contralesional motor hotspot at supra-maximal intensity (100% maximum stimulator output) while participants maintain sub-maximal contraction (50% maximum volitional contraction) of the ipsilateral paretic extensor digitorum communis muscle for 40 trials. Ipsilateral TMS produces transient suppression of on-going EMG activity, called ISP. ISP is analyzed using an algorithm that compares psotstimulus average rectified EMG to mean consecutive difference (MCD) of background EMG. A threshold of MCD x1.77 below mean background EMG is used to define ISP onset and offset. ISP duration is then calculated as a difference between onset and offset of the ISP.
Secondary Outcomes
- Change in Wolf Motor Function Test (WMFT) Functional Ability(Change between Baseline and Post-Test (average 6 weeks))
- Change in Wolf Motor Function Test (WMFT) Rate Paretic Limb(Change between Baseline and Post-Test (average 6 weeks))
- Change in Wolf Motor Function Test (WMFT) Rate Non-paretic Limb(Change between Baseline and Post-Test (average 6 weeks))
- Change in Wolf Motor Function Test (WMFT) Rate Paretic Limb Normalized to the Non-paretic Limb(Change between Baseline and Post-Test (average 6 weeks))
- Change in Stroke Impact Scale (SIS-16)(Change between Baseline and Post-Test (average 6 weeks))
- Change Resting State Functional Magnetic Resonance Imaging(rsfMRI)(Change between Baseline and Post-Test (average 6 weeks))
- Change in Ipsilateral MEPs (Motor Evoked Potentials)(Change between Baseline and Post-Test (average 6 weeks))
- Diffusion Tensor Imaging (DTI)(Baseline)
- Change in SULCS(Change between Baseline and Post-Test (average 6 weeks))