Clinical trial NCT03868410: A Novel Approach for Brain Stimulation in Severe Stroke
Official title: A Novel Approach for Brain Stimulation in Severe Stroke
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Stroke
Keywords: stroke
brain stimulation
TMS
Upper Limb
MRI
CVA
Rehabilitation
Lead sponsor: The Cleveland Clinic
Sponsor class: OTHER
Collaborators: name: American Heart Association
First posted: 2019-03-11
Enrollment: 16
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 pilot, randomized, assessor-blind clinical trial, an anticipated 24 patients will be assigned to either receive stimulation to a new brain target- contralesional dorsal premotor cortex (cPMd) located in the non-stroke hemisphere- or the conventional brain target- ipsilesional primary motor cortex (iM1) located in the stroke hemisphere. Stimulation will be delivered in conjunction with rehabilitation for 2 days a week for 6 weeks.
Primary purpose: TREATMENT

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).

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).

Primary outcomes:
measure: Change in Upper Extremity Fugyl-Meyer Score (UEFM)
timeFrame: Change between Baseline and Post-Test (average 6 weeks)
measure: Change in Inter-hemispheric Inhibition (IHI)
timeFrame: Change between Baseline and Post-Test (average 6 weeks)
Secondary outcomes:
measure: Change in Wolf Motor Function Test (WMFT) Functional Ability
timeFrame: Change between Baseline and Post-Test (average 6 weeks)
measure: Change in Wolf Motor Function Test (WMFT) Rate Paretic Limb
timeFrame: Change between Baseline and Post-Test (average 6 weeks)
measure: Change in Wolf Motor Function Test (WMFT) Rate Non-paretic Limb
timeFrame: Change between Baseline and Post-Test (average 6 weeks)
measure: Change in Wolf Motor Function Test (WMFT) Rate Paretic Limb Normalized to the Non-paretic Limb
timeFrame: Change between Baseline and Post-Test (average 6 weeks)
measure: Change in Stroke Impact Scale (SIS-16)
timeFrame: Change between Baseline and Post-Test (average 6 weeks)
measure: Change Resting State Functional Magnetic Resonance Imaging(rsfMRI)
timeFrame: Change between Baseline and Post-Test (average 6 weeks)
measure: Change in Ipsilateral MEPs (Motor Evoked Potentials)
timeFrame: Change between Baseline and Post-Test (average 6 weeks)
measure: Diffusion Tensor Imaging (DTI)
timeFrame: Baseline
measure: Change in SULCS
timeFrame: Change between Baseline and Post-Test (average 6 weeks)
Other outcomes:
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 Plow, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cunningham DA, Varnerin N, Machado A, Bonnett C, Janini D, Roelle S, Potter-Baker K, Sankarasubramanian V, Wang X, Yue G, Plow EB. Stimulation targeting higher motor areas in stroke rehabilitation: A proof-of-concept, randomized, double-blinded placebo-controlled study of effectiveness and underlying mechanisms. Restor Neurol Neurosci. 2015;33(6):911-26. doi: 10.3233/RNN-150574.
citation: Potter-Baker KA, Lin YL, Machado AG, Conforto AB, Cunningham DA, Sankarasubramanian V, Sakaie K, Plow EB. Variability of motor evoked potentials in stroke explained by corticospinal pathway integrity. Brain Stimul. 2018 Jul-Aug;11(4):929-931. doi: 10.1016/j.brs.2018.03.004. Epub 2018 Mar 9. No abstract available.
citation: Plow EB, Cunningham DA, Varnerin N, Machado A. Rethinking stimulation of the brain in stroke rehabilitation: why higher motor areas might be better alternatives for patients with greater impairments. Neuroscientist. 2015 Jun;21(3):225-40. doi: 10.1177/1073858414537381. Epub 2014 Jun 20.
citation: Sankarasubramanian V, Machado AG, Conforto AB, Potter-Baker KA, Cunningham DA, Varnerin NM, Wang X, Sakaie K, Plow EB. Inhibition versus facilitation of contralesional motor cortices in stroke: Deriving a model to tailor brain stimulation. Clin Neurophysiol. 2017 Jun;128(6):892-902. doi: 10.1016/j.clinph.2017.03.030. Epub 2017 Mar 21.
citation: Li X, Lin YL, Cunningham DA, Wolf SL, Sakaie K, Conforto AB, Machado AG, Mohan A, O'Laughlin K, Wang X, Widina M, Plow EB. Repetitive Transcranial Magnetic Stimulation of the Contralesional Dorsal Premotor Cortex for Upper Extremity Motor Improvement in Severe Stroke: Study Protocol for a Pilot Randomized Clinical Trial. Cerebrovasc Dis. 2022;51(5):557-564. doi: 10.1159/000521514. Epub 2022 Jan 20.