NCT03868410

A Novel Approach for Brain Stimulation in Severe Stroke

Completed EARLY_PHASE1 Results posted Last updated 5 June 2025

What this trial tests

EARLY_PHASE1 trial testing New Repetitive Magnetic Stimulation (rTMS) Approach in Stroke in 16 participants. Completed in 13 July 2023.

Timeline

1 April 2019

Primary endpoint
21 April 2023

13 July 2023

Quick facts

Lead sponsor	The Cleveland Clinic
Phase	EARLY_PHASE1
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	single
Primary purpose	treatment
Enrollment	16
Start date	1 April 2019
Primary completion	21 April 2023
Estimated completion	13 July 2023
Sites	1 location across United States

Drugs / interventions tested

• New Repetitive Magnetic Stimulation (rTMS) Approach
• Conventional Repetitive Magnetic Stimulation (rTMS) Approach

Conditions studied

• Stroke — all drugs for Stroke →

Sponsor

The Cleveland Clinic

Who can join

Adults 18 to 90, any sex, with Stroke. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change in Upper Extremity Fugyl-Meyer Score (UEFM) Primary · 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.)

Group	Value	95% CI
cPMD Repetitive Transcranial Magnetic Stimulation (rTMS) + Training	2.625	± 0.498
iM1 Repetitive Transcranial Magnetic Stimulation (rTMS) + Training	2.625	± 0.680

Change in Inter-hemispheric Inhibition (IHI) Primary · 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 rect

Group	Value	95% CI
cPMD Repetitive Transcranial Magnetic Stimulation (rTMS) + Training	-8.8774	± 4.62765
iM1 Repetitive Transcranial Magnetic Stimulation (rTMS) + Training	3.04521	± 4.62765

Change in Wolf Motor Function Test (WMFT) Functional Ability Secondary · Change between Baseline and Post-Test (average 6 weeks)

Change in Functional Ability (FA) from Baseline to Post-Test (average 6 weeks) is reported for the Wolf Motor Function Test. Functional ability (FA) to use the paretic upper limb in a variety of tasks will be assessed using WMFT. FA is scored on a scale from 0-5 with 0 not attempting the task at all and 5 being completely normal movement compared to non paretic limb. 15 items of WMFT are given a FA for the Paretic limb and then the score is averaged to give an overall FA for each participant.

Group	Value	95% CI
cPMD Repetitive Transcranial Magnetic Stimulation (rTMS) + Training	0.083	± 0.047
iM1 Repetitive Transcranial Magnetic Stimulation (rTMS) + Training	0.217	± 0.077

Change in Wolf Motor Function Test (WMFT) Rate Paretic Limb Secondary · Change between Baseline and Post-Test (average 6 weeks)

Change in Rate of the Paretic limb from Baseline to Post-Test (average 6 weeks) is reported for the Wolf Motor Function Test. Time to complete each task will be noted and converted to rate (60/Performance Time (sec)), optimized for measurement in moderately/severely-impaired patients. The rate will be calculated for the Paretic limb \[WMFT Rate (P)\]. The higher the rate the quicker they were able to complete the task.

Group	Value	95% CI
cPMD Repetitive Transcranial Magnetic Stimulation (rTMS) + Training	0.970	± 0.682
iM1 Repetitive Transcranial Magnetic Stimulation (rTMS) + Training	2.972	± 1.165

Change in Wolf Motor Function Test (WMFT) Rate Non-paretic Limb Secondary · Change between Baseline and Post-Test (average 6 weeks)

Change in Rate of the Non-paretic limb from Baseline to Post-Test (average 6 weeks) is reported for the Wolf Motor Function Test. Time to complete each task will be noted and converted to rate (60/Performance Time (sec)), optimized for measurement in moderately/severely-impaired patients. The rate will be calculated for the Non-paretic limb \[WMFT Rate (NP)\]. The higher the rate the quicker they were able to complete the task.

Group	Value	95% CI
cPMD Repetitive Transcranial Magnetic Stimulation (rTMS) + Training	2.552	± 1.048
iM1 Repetitive Transcranial Magnetic Stimulation (rTMS) + Training	3.098	± 0.977

Change in Wolf Motor Function Test (WMFT) Rate Paretic Limb Normalized to the Non-paretic Limb Secondary · Change between Baseline and Post-Test (average 6 weeks)

Change in the normalized Rate of the Paretic limb to the Non-paretic limb from Baseline to Post-Test (average 6 weeks) is reported for the Wolf Motor Function Test. Time to complete each task will be noted and converted to rate (60/Performance Time (sec)), optimized for measurement in moderately/severely-impaired patients. The rate will be calculated for the Paretic limb normalized to the Non-paretic limb \[WMFT Rate (P/NP)\]. The higher the rate the quicker they were able to complete the task.

Group	Value	95% CI
cPMD Repetitive Transcranial Magnetic Stimulation (rTMS) + Training	1.593	± 1.477
iM1 Repetitive Transcranial Magnetic Stimulation (rTMS) + Training	2.921	± 1.306

Change in Stroke Impact Scale (SIS-16) Secondary · Change between Baseline and Post-Test (average 6 weeks)

Change in total score between Baseline and Post-Test (average 6 weeks) is reported for the Stoke Impact Scale (SIS-16) for each group. Patient's perceived disability related to physical function will be indexed using the Stroke Impact Scale (SIS-16) which a subjective questionnaire asked to the subject pertaining of 16 questions. Each question is rated on scale from 1 to 5 and then the scores are totaled. Total scores can range from 16-80 (16 means that none of the functional tasks asked can be performed, a score of 80 means the subject has no issues at all performing any of the tasks asked).

Group	Value	95% CI
cPMD Repetitive Transcranial Magnetic Stimulation (rTMS) + Training	4.250	± 1.264
iM1 Repetitive Transcranial Magnetic Stimulation (rTMS) + Training	1.375	± 1.802

Adverse events — posted to ClinicalTrials.gov

Time frame: Each participant was monitored from Baseline assessment through 3 month follow-up (~5.5 months). Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

cPMD rTMS + Training

Serious: 0/8 (0%)

Deaths: 0/8

iM1 rTMS + Training

Serious: 0/8 (0%)

Deaths: 0/8

Other adverse events (6 terms — click to expand)

Reaction	System	cPMD rTMS + Training	iM1 rTMS + Training
headache	Nervous system disorders	—	—
neck pain	Musculoskeletal and connective tissue disorders	—	—
scalp irritation	Nervous system disorders	—	—
dizziness/lightheaded	Nervous system disorders	—	—
High Blood Pressure	Cardiac disorders	—	—
Fall at home	Musculoskeletal and connective tissue disorders	—	—

Data from ClinicalTrials.gov NCT03868410 adverse events section.

Sponsor's own description

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

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. 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.
   Li X, Lin YL, Cunningham DA, Wolf SL, et al · · 2022 · cited 9× · PMID 35051941 · DOI 10.1159/000521514