Clinical trial NCT05381740: A Novel Brain Stimulation for Bimanual Motor Function and Control in Chronic Stroke
Official title: A Novel Brain Stimulation for Bimanual Motor Function and Control in Chronic Stroke
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Stroke
Keywords: stroke
brain stimulation
TMS
Upper Limb
rehabilitation
MRI
CVA
neuromodulation
Lead sponsor: The Cleveland Clinic
Sponsor class: OTHER
Collaborators: name: American Heart Association
First posted: 2022-05-19
Enrollment: 17
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 prospective randomized controlled trial, an anticipated 18 stroke survivors with chronic (≥6 months) upper limb impairment will receive real or sham stimulation to the non-stroke hemisphere (cHMC). Stimulation will be delivered in conjunction with upper limb rehabilitation for 2 days a week for 6 weeks.
Primary purpose: TREATMENT

Brief summary: The long-term goal of this project is to develop and test upper Iimb rehabilitation interventions that can improve bimanual motor function, or the ability to use both arms and hands together, for stroke survivors with moderate to severe impairment.

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
* Baseline testing (4 visits total): 1 visit each for MRI, upper limb and bimanual motor function test, bimanual motor control, and neurophysiology related to control of the upper limbs
* Repeat baseline testing (4 visits total) of MRI, upper limb and bimanual motor function test, bimanual motor control, and neurophysiology related to control of the upper limbs
* 12 intervention visits during which patients will receive upper limb therapy in conjunction with non-invasive brain stimulation
* Repeat testing (4 visits total) of MRI, upper limb and bimanual motor function test, bimanual motor control, and neurophysiology related to control of the upper limbs
* A follow-up visit 1 month after the completion of interventions

Detailed description: In a pilot randomized controlled clinical trial, 18 stroke survivors more than 6 months after stroke onset, and have upper limb impairment will be enrolled. Participants will be randomized to receive a form of non-invasive brain stimulation called repetitive transcranial magnetic stimulation or rTMS or sham rTMS. Real or sham rTMS will be delivered over an area in the brain called the higher motor cortices within the stroke-unaffected hemisphere, cHMC for short. This area (cHMC) is important for using both arms and hands together, or bimanual motor function. Real or sham cHMC rTMS will be given prior to upper limb therapy twice a week for 6 weeks in the lab. The investigators will measure bimanual motor function and control twice at the beginning, once after the 6-week treatment and once at 1-month after treatment. The investigators will also test possible mechanisms related to the treatment using brain functional MRI and TMS twice at the beginning and once after 6-week treatment.

Eligibility criteria: Inclusion Criteria:

* Age 18-90 yrs
* ≥6 months since first clinical stroke
* Impairment of the paretic hand, indicated by a score of \<= 11 out of 14 on the hand section of UEFM
* Sufficient range of motion in the wrist and fingers for functional task practice: have at least 10 degrees active wrist extension, 10 degrees active thumb abduction/extension, and 10 degrees active extension in at least 2 additional digits
* Sufficient active shoulder and elbow movement to volitionally position the paretic hand in the workspace for table-top task practice

Exclusion Criteria:

* Brainstem or cerebellar stroke
* Bilateral strokes or multiple strokes affecting sensorimotor structures
* Cognitive impairment (Mini-Mental State Examination \<24)
* Severe impairment of the paretic hand that limits functional task practice (UEFM hand score \< 4 out of 14)
* Severe spasticity (Modified Ashworth Scale \>3) or upper limb contracture
* Occupational therapy or upper limb Botox completed ≤ 2 months prior
* Contraindications to TMS or MRI (e.g. metal implant in head, seizure history, cardiac pacemaker)

Primary outcomes:
measure: Change in Bimanual Assessment Measure (BAM)
timeFrame: Baseline (0 weeks and 2 weeks), after intervention(up to 7 weeks) and after end of 1 month of follow-up.
Secondary outcomes:
measure: Change in Bimanual Grip Force Modulation Task
timeFrame: Baseline (0 weeks and 2 weeks), after intervention(up to 7 weeks) and after end of 1 month of follow-up.
measure: Change in ABILHAND
timeFrame: Baseline (0 weeks and 2 weeks), after intervention(up to 7 weeks) and after end of 1 month of follow-up.
measure: Change in Upper Extremity Fugyl-Meyer Score (UEFM)
timeFrame: Baseline (0 weeks and 2 weeks), after intervention(up to 7 weeks) and after end of 1 month of follow-up.
measure: Change in Wolf Motor Function Test (WMFT)
timeFrame: Baseline (0 weeks and 2 weeks), after intervention(up to 7 weeks) and after end of 1 month of follow-up.
measure: Change Resting State Functional Magnetic Resonance Imaging(rsfMRI)
timeFrame: Baseline (0 weeks and 2 weeks), after intervention(up to 7 weeks)
measure: Change in excitability of cortical and corticospinal physiology (TMS)
timeFrame: Baseline (0 weeks and 2 weeks), after intervention(up to 7 weeks)
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Lerner Research Institute, Cleveland Clinic Foundation
state: Ohio
Study officials:
affiliation: The Cleveland Clinic
name: Ela Plow, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Haaland KY, Mutha PK, Rinehart JK, Daniels M, Cushnyr B, Adair JC. Relationship between arm usage and instrumental activities of daily living after unilateral stroke. Arch Phys Med Rehabil. 2012 Nov;93(11):1957-62. doi: 10.1016/j.apmr.2012.05.011. Epub 2012 May 24.
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: Liao WW, Whitall J, Wittenberg GF, Barton JE, McCombe Waller S. Not all brain regions are created equal for improving bimanual coordination in individuals with chronic stroke. Clin Neurophysiol. 2019 Aug;130(8):1218-1230. doi: 10.1016/j.clinph.2019.04.711. Epub 2019 May 13.