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

NCT ID: NCT05381740

Last Updated: 2024-06-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-08
• Study Completion Date: 2024-01-01

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.

Conditions

Stroke

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

cHMC rTMS + Upper Limb Training Training

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

Group Type: EXPERIMENTAL

Novel rTMS Approach

Intervention Type: 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.

Sham rTMS + Upper Limb Training Training

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

Group Type: SHAM_COMPARATOR

Sham rTMS Approach

Intervention Type: 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.

Interventions

Novel rTMS Approach

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.

Intervention Type: DEVICE

Sham rTMS Approach

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.

Intervention Type: DEVICE

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

American Heart Association

OTHER

Sponsor Role: collaborator

The Cleveland Clinic

OTHER

Sponsor Role: lead

Responsible Party

Ela B. Plow

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ela Plow, PhD

Role: PRINCIPAL_INVESTIGATOR

The Cleveland Clinic

Locations

Lerner Research Institute, Cleveland Clinic Foundation

Cleveland, Ohio, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 22634230 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 28402865 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 31163366 (View on PubMed)

Other Identifiers

22-074

Identifier Type: -

Identifier Source: org_study_id