A Novel Brain Stimulation for Bimanual Motor Function and Control in Chronic Stroke

NCT05381740 | Completed Early Phase 1 FDA Device

• 1 other identifier: 22-074
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

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

Conditions

Stroke

Keywords

stroke; brain stimulation; TMS; Upper Limb; rehabilitation; MRI; CVA; neuromodulation

Outcome Measures

Primary Outcomes (1)

• Change in Bimanual Assessment Measure (BAM)

  Measure of the functional ability to perform 11 bimanual tasks scoring the spontaneous role of the affected hand, timing, and quality of movement.

  Baseline (0 weeks and 2 weeks), after intervention(up to 7 weeks) and after end of 1 month of follow-up.

Secondary Outcomes (6)

• Change in Bimanual Grip Force Modulation Task

  Baseline (0 weeks and 2 weeks), after intervention(up to 7 weeks) and after end of 1 month of follow-up.

• Change in ABILHAND

  Baseline (0 weeks and 2 weeks), after intervention(up to 7 weeks) and after end of 1 month of follow-up.

• Change in Upper Extremity Fugyl-Meyer Score (UEFM)

  Baseline (0 weeks and 2 weeks), after intervention(up to 7 weeks) and after end of 1 month of follow-up.

• Change in Wolf Motor Function Test (WMFT)

  Baseline (0 weeks and 2 weeks), after intervention(up to 7 weeks) and after end of 1 month of follow-up.

• Change Resting State Functional Magnetic Resonance Imaging(rsfMRI)

  Baseline (0 weeks and 2 weeks), after intervention(up to 7 weeks)

Study Arms (2)

cHMC rTMS + Upper Limb Training Training

EXPERIMENTAL

Real Repetitive Transcranial Magnetic Stimulation given to facilitate the Contralesional Higher Motor Cortices+ Upper Limb Training

Device: Novel rTMS Approach

Sham rTMS + Upper Limb Training Training

SHAM COMPARATOR

Sham Repetitive Transcranial Magnetic Stimulation over Contralesional Higher Motor Cortices+ Upper Limb Training

Device: Sham rTMS Approach

Interventions

Novel rTMS Approach DEVICE

Participants in this arm will receive rTMS-based facilitation of the contralesional higher motor cortices located in the non-stroke hemisphere before the start of each rehabilitation session. High-frequency rTMS (5Hz) will be delivered using 42 10 second trains of 50 pulses each (total 2100 pulses) for a period of 22 minutes. Immediately after the completion of rTMS, participants will undergo therapist-guided upper limb therapy for a total of one hour. Participants will receive these interventions 2 days a week for 6 weeks for a total of 12 sessions.

cHMC rTMS + Upper Limb Training Training

Sham rTMS Approach DEVICE

Participants in this arm will receive sham rTMS given over the contralesional higher motor cortices located in the non-stroke hemisphere before the start of each rehabilitation session. Immediately after the completion of sham rTMS, participants will undergo therapist-guided upper limb therapy for a total of one hour. Participants will receive these interventions 2 days a week for 6 weeks for a total of 12 sessions.

Sham rTMS + Upper Limb Training Training

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• The Cleveland Clinic: lead
• American Heart Association: collaborator

Study Sites (1)

Lerner Research Institute, Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Related Publications (3)

• 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.

  PMID: 22634230 BACKGROUND

• 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.

  PMID: 28402865 BACKGROUND

• 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.

  PMID: 31163366 BACKGROUND

MeSH Terms

Conditions

Stroke

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Ela Plow, PhD

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Subjects will be told they will receive brain stimulation, but will be given no indication as to whether they will receive real or sham stimulation. Investigators analyzing functional outcome data, neurophysiology data and MRI data will receive coded data that conceals the identity of the subject. Therapists involved in training patients will not know which type of rTMS the participant receives.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: 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.

Study Record Dates

• First Submitted: May 16, 2022
• First Posted: May 19, 2022
• Study Start: March 8, 2022
• Primary Completion: December 6, 2023
• Study Completion: January 1, 2024
• Last Updated: June 3, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)