Temporal Interference Stimulation for Upper-Limb Motor Recovery in Early Subacute Stroke (TIMES)

November 3, 2026 updated by: Xuanwu Hospital, Beijing

Effects of Transcranial Temporal Interference Stimulation on Upper-Limb Motor Recovery in Early Subacute Ischemic Stroke: A Randomized, Double-Blind, Sham-Controlled Pilot Trial

This study aims to test whether transcranial temporal interference stimulation (tTIs) can improve upper limb motor function in patients in the early subacute stage after acute ischemic stroke. Participants will be randomly assigned to receive either active tTIs treatment or sham stimulation. All subjects will receive routine rehabilitation. The treatment will be given once daily for 20 consecutive days. Researchers will assess upper limb motor function before treatment, during the intervention and after the treatment course to compare the effect between the two groups. Safety will also be monitored throughout the study.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

This prospective, two-center, randomized, double-blind, parallel-group, exploratory pilot randomized controlled trial will enroll 60 right-handed patients with first-ever unilateral anterior circulation acute ischemic stroke in the early subacute phase (7 days to 3 months after stroke onset). All participants will have received reperfusion therapy and exhibit upper-limb motor impairment, defined as a Fugl-Meyer Assessment of the Upper Extremity (FMA-UE) score of ≤42. Participants will be randomly assigned in a 1:1 ratio to either the active tTIS group or the sham-stimulation group.All participants will receive standard rehabilitation therapy once daily for 20 consecutive days. In addition to routine rehabilitation, participants in the active tTIS group will receive active stimulation targeting the cerebellar dentate nucleus. Participants in the sham group will undergo an identical setup, including EEG cap placement, but will receive sham stimulation without effective amplitude-modulated output. Each stimulation session will last 20 minutes. Participants and outcome assessors will be blinded to group allocation, whereas the treatment operator will remain unblinded. Blinding will be maintained until the database is locked.

Assessments will be conducted at baseline, immediately before and after the first intervention session, on days 7 and 14, after completion of the 20-session intervention, and at the 3-month follow-up. Clinical assessments, multimodal magnetic resonance imaging (MRI), electroencephalography (EEG), and transcranial magnetic stimulation (TMS) examinations will be performed at prespecified time points to characterize changes in motor function, brain structural and functional connectivity, and cortical excitability. Adverse events will be systematically recorded and monitored throughout the trial.

This study aims to investigate the safety and feasibility of cerebellar dentate nucleus-targeted tTIS as an adjunct to routine rehabilitation and to obtain preliminary evidence of its efficacy in improving upper-limb motor function in patients with acute ischemic stroke during the early subacute phase. In addition, multimodal neuroimaging and neurophysiological assessments will be used to explore the potential neural mechanisms underlying tTIS-induced motor recovery.

Study Type

Interventional

Enrollment (Estimated)

60

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
      • Beijing, China, 100053
        • Xuanwu Hospital, Capital Medical University
        • Principal Investigator:
          • Liqun Jiao
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. First-ever ischemic stroke occurring 7 days to 3 months before enrollment.
  2. Unilateral anterior-circulation ischemic stroke confirmed by CT or MRI.
  3. Receipt of reperfusion therapy.
  4. Age 18-80 years.
  5. Upper-limb motor impairment, defined as an FMA-UE score of ≤42.
  6. Right-handedness, as determined by the Edinburgh Handedness Inventory.
  7. Ability to understand and communicate adequately, willingness to participate, and provision of written informed consent.

Exclusion Criteria:

  1. Previous history of stroke, either ischemic or hemorrhagic.
  2. Severe cognitive impairment or psychiatric symptoms.
  3. Bilateral brain lesions or other neurological disorders, including Parkinson's disease, epilepsy, or brain tumors.
  4. Severe cardiac, pulmonary, hepatic, renal, or other major organ dysfunction.
  5. Skull defects.
  6. Increased intracranial pressure.
  7. Contraindications to MRI, including incompatible intracranial or external metal objects or implanted devices such as pacemakers or infusion pumps.
  8. Current participation in another clinical trial.
  9. Inability to complete the treatment or follow-up procedures, poor adherence, or adverse reactions to electrical stimulation that prevent continued participation.
  10. Pregnancy or breastfeeding.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Active tTIs Group

Participants will receive individualized active transcranial temporal interference stimulation targeting the cerebellar dentate nucleus contralateral to the cerebral lesion, 20 minutes per session, once daily for 20 consecutive days, combined with routine rehabilitation therapy.
Device: Transcranial Temporal Interference Stimulation (tTIs)

Individualized active stimulation will be administered via the NervioX-1000 temporal interference stimulation system. The cerebellar dentate nucleus contralateral to the cerebral lesion is targeted using an electrode montage and current ratio optimized based on each participant's structural magnetic resonance imaging and finite-element electric field modeling. Stimulation parameters are kept constant throughout the intervention. Each session lasts 20 minutes, including 30-second ramp-up and ramp-down periods, with treatment administered once daily for 20 consecutive days.
Sham Comparator: Sham tTIs Group

Participants will receive sham transcranial temporal interference stimulation followed by the same standardized routine rehabilitation therapy. The sham procedure will use the same device, electrode montage, session duration, and ramp sensations as active stimulation but will not deliver sustained active stimulation.
Device: Sham Transcranial Temporal Interference Stimulation (Sham tTIs)

Sham stimulation will be delivered using the same device, individualized electrode montage, positioning procedures, and session schedule as active stimulation. The device will reproduce the initial ramp-up and brief stimulation sensations and will then ramp down without delivering sustained active stimulation. A brief terminal ramp will reproduce end-of-session sensations. Each sham session lasts 20 minutes, including 30-second ramp-up and ramp-down periods, administered once daily for 20 consecutive days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Fugl-Meyer Assessment of Upper Extremity (FMA-UE)
Time Frame: 20 days after the start of intervention

Change in Fugl-Meyer Assessment of Upper Extremity score, range 0-66; higher score indicates better upper limb motor function.
20 days after the start of intervention

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Action Research Arm Test (ARAT)
Time Frame: 20 days after the start of intervention

The Action Research Arm Test scale is used to assess upper limb activity and functional ability. Total possible scores range from 0 to 57. Higher scores indicate better upper limb functional performance.
20 days after the start of intervention
Global disability: Modified Rankin Scale (mRS)
Time Frame: 20 days after the start of intervention

The Modified Rankin Scale is an ordinal scale used to assess functional disability and dependence in activities of daily living after stroke. Scores range from 0 to 6. Higher scores indicate worse functional outcome, with a score of 6 representing death.
20 days after the start of intervention
National Institutes of Health Stroke Scale (NIHSS)
Time Frame: 20 days after the start of intervention

The National Institutes of Health Stroke Scale is used to quantify neurological deficit after stroke. Total possible scores range from 0 to 42. Higher scores indicate more severe neurological impairment (worse outcome).
20 days after the start of intervention
Multimodal magnetic resonance imaging (MRI)
Time Frame: Assessments were performed at 1 and 20 days after the initiation of the intervention

Multimodal MRI, including functional MRI (fMRI), diffusion tensor imaging (DTI), and three-dimensional T1-weighted imaging, is acquired to assess structural-functional coupling of the dentato-thalamo-cortical (DTC) pathway. Structural-functional connectivity (SFC) is calculated as the coupling index between DTI-derived structural connectivity and resting-state fMRI functional connectivity along the DTC pathway. Higher SFC values indicate stronger structural-functional coupling of this pathway.
Assessments were performed at 1 and 20 days after the initiation of the intervention
Electroencephalography (EEG)
Time Frame: Assessments were performed at 1 and 20 days after the initiation of the intervention

EEG is recorded synchronously during temporal interference (TI) stimulation. Inter-trial phase coherence (ITPC) is computed to quantify the consistency of phase-locked cortical responses across trials, ranging from 0 to 1. Higher ITPC indicates more reliable phase-locked cortical activation.
Assessments were performed at 1 and 20 days after the initiation of the intervention
Transcranial Magnetic Stimulation (TMS)-Induced Motor Evoked Potentials (MEP)
Time Frame: Assessments were performed at 1 and 20 days after the initiation of the intervention

Single-pulse transcranial magnetic stimulation (TMS) is delivered over the primary motor cortex. Surface electromyography records motor evoked potentials from the target muscle. Peak-to-peak MEP amplitude is measured in microvolts (μV). Larger amplitude indicates higher corticospinal excitability.
Assessments were performed at 1 and 20 days after the initiation of the intervention

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
adverse events
Time Frame: 20 days after the start of intervention

The incidence and severity of adverse events, including adverse events related to the intervention, assessed throughout the intervention period.
20 days after the start of intervention

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Xuanwu Hospital, Beijing

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

November 1, 2026

Primary Completion (Estimated)

November 1, 2027

Study Completion (Estimated)

February 1, 2028

Study Registration Dates

First Submitted

October 19, 2026

First Submitted That Met QC Criteria

October 25, 2026

First Posted (Actual)

October 27, 2026

Study Record Updates

Last Update Posted (Actual)

November 6, 2026

Last Update Submitted That Met QC Criteria

November 3, 2026

Last Verified

October 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TIMES

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Individual participant data (IPD) will not be shared. The data involves sensitive personal health information of participants, and there is no plan to release the individual-level raw data to other researchers due to privacy and data security considerations.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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