NCT05479006

Brief Summary

Significant motor impairments occur in 80% of individuals after moderate to severe stroke and impact the body side to the lesioned hemisphere. Typical motor impairments involve loss of dexterity with highly prevalent upper limb flexion synergy. Advances in treating flexion synergy impairments have been hampered by a lack of precision rehabilitation. Previous studies suggest and support the role of cortico-reticulospinal tract (CRST) hyperexcitability in post-stroke flexion synergy. CRST hyperexcitability is often caused by damage to the corticospinal tract (CST). We hypothesize that: 1) inhibiting the contralesional dorsal premotor cortex (cPMd) will directly reduce the CRST hyperexcitability and thus, reduce the expression of the flexion synergy; 2) facilitating the ipsilesional primary motor cortex (iM1) will improve the excitability of the damaged CST, therefore reducing the CRST hyperexcitability and the flexion synergy. we propose to use a novel targeted high-definition tDCS (THD-tDCS) to specifically modulate the targeted cortical regions for testing his hypothesis, via the following aims: Aim 1. Evaluate the effect of cathodal THD-tDCS over the cPMd on reducing the CRST hyperexcitability and the expression of flexion synergy. Aim 2. Evaluate the effect of anodal THD-tDCS over the iM1 on improving the excitability of the CST, and determine whether this, thus, also reduces the CRST hyperexcitability and the flexion synergy. Aim 3. Evaluate the confluence effect of bilateral THD-tDCS, i.e., simultaneous cathodal stimulation over the cPMd and anodal over the iM1.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
30

participants targeted

Target at P25-P50 for not_applicable stroke

Timeline
2mo left

Started Sep 2022

Longer than P75 for not_applicable stroke

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress96%
Sep 2022Jun 2026

First Submitted

Initial submission to the registry

July 26, 2022

Completed
2 days until next milestone

First Posted

Study publicly available on registry

July 28, 2022

Completed
2 months until next milestone

Study Start

First participant enrolled

September 30, 2022

Completed
3.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 30, 2026

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 30, 2026

Last Updated

December 19, 2025

Status Verified

December 1, 2025

Enrollment Period

3.8 years

First QC Date

July 26, 2022

Last Update Submit

December 15, 2025

Conditions

Stroke

Keywords

StrokeNon-invasive Brain StimulationMovement Impairment

Outcome Measures

Primary Outcomes (2)

  • Change in Transcranial Magnetic Stimulation-Evoke Motor-evoked Potential 1: Ispilesional stimulation in the brain and contralateral response in the muscle

    This is a neurophysiological measure that determines the use of the ipsilesional corticospinal tract.

    Baseline (initial visit), before (within 30 min range) and immediately after (within 30 min range) the intervention

  • Change in Transcranial Magnetic Stimulation-Evoke Motor-evoked Potential 2: Contralesional stimulation in the brain and ipsilateral response in the muscle

    This is a neurophysiological measure that determines the use of the contralesional cortico-reticulospinal tract.

    Baseline (initial visit), before (within 30 minutes range) and immediately after (within 30 minutes range) the intervention

Secondary Outcomes (2)

  • Change in a subset of Fugl-Meyer Upper Extremity assessment which is mainly related to the muscle synergies

    Baseline (initial visit), before (within 30 minutes range) and immediately after (within 30 minutes range) the intervention

  • Change in Fugl-Meyer Upper Extremity assessment

    Baseline (initial visit), before (within 30 minutes range) and immediately after (within 30 minutes range) the intervention

Other Outcomes (1)

  • Modified Ashworth Scale

    Baseline (initial visit), before (within 30 minutes range) and immediately after (within 30 minutes range) the intervention

Study Arms (4)

Anodal stimulation

ACTIVE COMPARATOR

Anodal stimulation targets the primary motor cortex (arm area) in the lesioned hemisphere, sham on the contralesional hemisphere.

Device: Transcranial direct current stimulation (high- definition)

Cathodal stimulation

ACTIVE COMPARATOR

Cathodal stimulation targets the dorsal premotor cortex (arm area) in the contralesional hemisphere, sham on the lesioned hemisphere.

Device: Transcranial direct current stimulation (high- definition)

Bilateral Stimulation

ACTIVE COMPARATOR

Anodal stimulation targets the primary motor cortex (arm area) in the lesioned hemisphere and cathodal stimulation targets the dorsal premotor cortex (arm area) in the contralesional hemisphere at the same time.

Device: Transcranial direct current stimulation (high- definition)

Sham stimulation

SHAM COMPARATOR

Sham stimulation to both hemisphere of the brain

Device: Transcranial direct current stimulation (high- definition)

Interventions

Transcranial direct current stimulation (high- definition)DEVICE

20 minutes, 2 mA stimulation.

Anodal stimulationBilateral StimulationCathodal stimulationSham stimulation

Eligibility Criteria

Age18 Years - 90 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Paresis confined to one side, with substantial motor impairment of the paretic upper limb
  • Capacity to provide informed consent

You may not qualify if:

  • Muscle tone abnormalities and motor or sensory impairment in the non-paretic limb
  • Severe wasting or contracture or significant sensory deficits in the paretic upper limb
  • Severe cognitive or affective dysfunction that prevents normal communication and understanding of consent or instruction
  • Severe concurrent medical problems (e.g. cardiorespiratory impairment)
  • Using a pacemaker
  • Metal implants in the head
  • Known adverse reactions to TMS and tDCS
  • Pregnant

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Carle Foundation Hospital

Urbana, Illinois, 61801, United States

RECRUITING

Related Publications (4)

  • Williamson JN, James SA, Mulyana B, Kim S, He D, Li S, Sidorov EV, Yang Y. Quantitative EEG Metrics for Determining HD-tDCS Induced Alteration of Brain Activity in Stroke Rehabilitation. Restor Neurol Neurosci. 2024 Nov;42(3-4):209-221. doi: 10.1177/09226028251347427. Epub 2025 Jun 16.

    PMID: 40518976BACKGROUND

  • McPherson JG, Stienen AH, Drogos JM, Dewald JP. Modification of Spastic Stretch Reflexes at the Elbow by Flexion Synergy Expression in Individuals With Chronic Hemiparetic Stroke. Arch Phys Med Rehabil. 2018 Mar;99(3):491-500. doi: 10.1016/j.apmr.2017.06.019. Epub 2017 Jul 24.

    PMID: 28751255BACKGROUND

  • Peng RH, He D, James SA, Williamson JN, Skadden C, Jain S, Hassaneen W, Miranpuri A, Kaur A, Sarol JN, Yang Y. Determining the effects of targeted high-definition transcranial direct current stimulation on reducing post-stroke upper limb motor impairments-a randomized cross-over study. Trials. 2024 Jan 9;25(1):34. doi: 10.1186/s13063-023-07886-w.

    PMID: 38195605BACKGROUND

  • Williamson JN, James SA, He D, Li S, Sidorov EV, Yang Y. High-definition transcranial direct current stimulation for upper extremity rehabilitation in moderate-to-severe ischemic stroke: a pilot study. Front Hum Neurosci. 2023 Oct 12;17:1286238. doi: 10.3389/fnhum.2023.1286238. eCollection 2023.

    PMID: 37900725BACKGROUND

MeSH Terms

Conditions

Stroke

Interventions

Transcranial Direct Current Stimulation

Condition Hierarchy (Ancestors)

Cerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular DiseasesCardiovascular Diseases

Intervention Hierarchy (Ancestors)

Electric Stimulation TherapyTherapeuticsConvulsive TherapyPsychiatric Somatic TherapiesBehavioral Disciplines and ActivitiesElectroshockPsychological Techniques

Central Study Contacts

Yuan Yang, PhD

CONTACT

217-244-5870yuan.yang@carle.com

Sanjiv Jain, MD

CONTACT

217-383-3800sanjiv.jain@carle.com

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, OUTCOMES ASSESSOR
Masking Details
The sequence of the stimulations will be randomized (generated in RedCap) and double-blinded (assessor and participants).
Purpose
BASIC SCIENCE
Intervention Model
CROSSOVER
Model Details: This sham-controlled cross-over study design will include four visits: 1) anodal stimulation targeting the ipsilesional hemisphere, 2) cathodal one at the contralesional hemisphere, 3) bilateral stimulation with anodal on the ipsilesional hemisphere and cathodal on the contralesional hemisphere and 4) a sham stimulation visit. After each intervention, there will be at least 2 weeks wash-out period before participants receive the next intervention and assessments.
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 26, 2022

First Posted

July 28, 2022

Study Start

September 30, 2022

Primary Completion (Estimated)

June 30, 2026

Study Completion (Estimated)

June 30, 2026

Last Updated

December 19, 2025

Record last verified: 2025-12

Data Sharing

IPD Sharing
Will not share

We are committed to enhancing the value of research and furthering the advancement of public knowledge. We recognize that the public dissemination of our scientific results can facilitate the creation of collaborative efforts with domestic and international collaborators. Furthermore, we recognize that the proposed project may result in novel ideas for new methods, technologies, and data that could benefit the entire research community. Therefore, final research data will be shared openly and timely in accordance with the most recent NIH guidelines (http://grants.nih.gov/grants/policy/data\_sharing/) while being mindful that the confidentiality and privacy of participants in research must be protected at all times.

Locations

US(1)