Study on the Effectiveness and Safety of Temporal Interference Stimulation in Treating Patients With Severe Consciousness Disorders

December 8, 2025 updated by: Xuehai Wu, Huashan Hospital
Investigating the efficacy and safety of temporal interference stimulation for patients with disorders of consciousness.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Based on the central loop hypothesis, deep brain stimulation (DBS) represents a commonly utilized neuro-modulation stimulation technology for disorders of consciousness (DOC). It was initially employed in Europe in 1968 for treating DOC. Some patients can regain functional communication capabilities and even resume family life. Nevertheless, as a neurosurgical intervention, DBS implantation entails significant surgical risks and potential complications (such as cerebral edema in the surgical area, secondary cerebral hemorrhage, secondary epilepsy, postoperative brain abscess, pulse generator shutdown or circuit malfunction, displacement of stimulation electrodes or extension leads, rejection reactions), and incurs substantial costs, imposing a heavy burden on patients' families and the national medical insurance fund. Traditional non-invasive brain stimulation methods, such as transcranial alternating or direct current stimulation, although not requiring surgery, have limited focusing capacity and the ability to stimulate deep brain structures. Hence, researchers have been in pursuit of approaches to precisely and effectively stimulate deep brain regions without the need for surgery.

In 2017, the concept of temporal interference (TI) stimulation, a novel non-invasive method for regulating deep brain regions was put forward . The fundamental principle of TI stimulation is that two interfering high-frequency signals will generate a low-frequency amplitude-modulated electric field, which can drive the discharge of deep brain neurons. Furthermore, by fixing the sum of the input currents of two pairs of electrodes and altering the current input ratio of the two pairs of electrodes, the movement of the mouse's forepaws, whiskers, and ears without modifying the spatial position of the electrodes could be achieved. Therefore, TI stimulation enables the flexible movement of the stimulation target area within the brain without electrode displacement. Despite the fact that research on TI technology is still in its nascent stage, this method has demonstrated substantial potential in neuroscience and clinical therapy.

Consequently, the objective of this multicenter randomized controlled trial is to assess the therapeutic effect of temporal interference stimulation in awakening patients with severe disorders of consciousness and verify its safety. Simultaneously, it aims to clarify issues such as the clinical application indications, operational parameters of TI. This will facilitate a deeper comprehension of the effectiveness, clinical application indications, operational parameters, and treatment plans of this emerging neuro-modulation technology as a means of awakening treatment, and promote the advancement of diagnosis and treatment technologies for patients with severe disorders of consciousness.

Study Type

Interventional

Enrollment (Estimated)

20

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 Contact Backup

Study Locations

  • China
    • Shanghai Municipality
      • Shanghai, Shanghai Municipality, China, 200000
        • Recruiting
        • Department of neurological rehabilitation, Shanghai First Rehabilitation Hospital, Tongji University
        • Contact:
      • Shanghai, Shanghai Municipality, China, 200000
        • Recruiting
        • Department of Neurosurgery, Huashan Hospital, Fudan University
        • 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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Severe consciousness disorder patients aged 18 to 75 years old, regardless of gender;
  • Patients with severe consciousness disorders, namely a minimally conscious state or vegetative state that lasts for 28 days or more;
  • Patients with normal body temperature, stable vital signs, spontaneous breathing, tracheotomy without the use of a metal cannula and with a small amount of sputum, and who are eligible for magnetic resonance imaging (MRI) examination;
  • Written informed consent obtained from the patient's family members in advance.

Exclusion Criteria:

  • Individuals with a previous history of significant neuropsychiatric and other major disorders such as those involving the heart, lung, liver, and kidney;
  • Those who have undergone V-P shunt or Ommaya reservoir implantation and other procedures that may influence the analysis of magnetic resonance scanning signals;
  • Patients who are scheduled for V-P shunt or Ommaya reservoir implantation in the near future;
  • Pregnant women;
  • Those who have participated in other drug or device clinical trials;
  • Patients with poorly controlled epilepsy in the recent period;
  • Those with infections at the TI stimulation site or compromised skin integrity at the electrode placement site;
  • Those currently taking medications prone to inducing epilepsy, such as quinolone drugs;
  • Those with intracranial infections, intracranial tumors, or metallic objects within the cranium;
  • Those allergic to electrode gel or adhesives;
  • Those with implanted electronic devices within the body;
  • Those with severe cardiac disorders and those equipped with cardiac pacemakers.

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: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: TI stimulation group
The two high-frequency electric fields of the TI device are set at different frequencies, thereby resulting in the generation of a low-frequency electric field that is capable of triggering brain physiological responses. The duration is 10 minutes.
Procedure: TI Stimulation
Participants will accept the TI stimulus for one month
Sham Comparator: Sham TI stimulation group
The two high-frequency electric fields of the TI device are set to be completely of the same frequency (2000Hz), thus no low-frequency electric field is produced and no cerebral physiological responses are elicited. The duration lasts for 10 minutes.
Procedure: Sham Stimulation
Participants will accept the sham TI stimulus for one month

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Effective rate of awakening
Time Frame: Stimulation for 1 month
The CRS-R is employed, with a minimum of 5 CRS-R assessments conducted at each follow-up time point, accompanied by simultaneous video recording. And the highest value is scored as a state of consciousness. The clinical assessment of participants' consciousness is deemed significantly improved when it fulfills the following criteria: a) MCS- recover to consciousness level of MCS+ or higher; b) Vegetative state(VS) recover to consciousness level of MCS- or higher; c) MCS status (MCS- or MCS+) recover to emergence from MCS (restoration of functional communication).
Stimulation for 1 month

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The difference of CRS-R scale relative to baseline between TI group and sham group
Time Frame: Stimulation begin for 14 days, 1 month and 3 months
The Coma Recovery Scale-Revised (CRS-R) is a standardized neurobehavioral assessment measure designed for use in patients with disorders of consciousness. It has good validity, reliability and practicability.
Stimulation begin for 14 days, 1 month and 3 months
The difference of Simplified Evaluation of CONsciousness Disorders (SECONDs) scale relative to baseline between TI group and sham group
Time Frame: Stimulation begin for 14 days, 1 month and 3 months
The SECONDs is a fast tool to assess consciousness in brain-injured patients. The minimum score is 0 and the maximum is 8, higher scores mean a better outcome.
Stimulation begin for 14 days, 1 month and 3 months
The difference of modified Ashworth scale relative to baseline between TI group and sham group
Time Frame: Stimulation begin for 14 days, 1 month and 3 months
The modified Ashworth scale is the most universally accepted clinical tool used to measure the increase of muscle tone. The minimum grade is 0 and the maximum is 4, higher scores mean a worse outcome.
Stimulation begin for 14 days, 1 month and 3 months
The difference of Nociception Coma Scale-Revised (NCS-R) scale relative to baseline between TI group and sham group
Time Frame: Stimulation begin for 14 days, 1 month and 3 months
The NCS-R was developed to help assess pain in patients with disorders of consciousness (DOC). Several studies have shown its sensitivity in assessing response to acute noxious stimuli. The minimum score is 0 and the maximum is 12, higher scores mean a better outcome.
Stimulation begin for 14 days, 1 month and 3 months
The difference of effective rate of awakening between TI group and sham group by CRS-R scale
Time Frame: Stimulation begin for 1 month and 3 months
The Coma Recovery Scale-Revised (CRS-R) is a standardized neurobehavioral assessment measure designed for use in patients with disorders of consciousness. It has good validity, reliability and practicability.
Stimulation begin for 1 month and 3 months
The difference of effective rate of awakening between TI group and sham group by Simplified Evaluation of CONsciousness Disorders (SECONDs) scale
Time Frame: Stimulation begin for 1 month and 3 months
The SECONDs is a fast tool to assess consciousness in brain-injured patients. The minimum score is 0 and the maximum is 8, higher scores mean a better outcome.
Stimulation begin for 1 month and 3 months
The difference of recovery trajectories of consciousness level between TI group and Sham group
Time Frame: Stimulation for 3-month-stimulation
Stimulation for 3-month-stimulation

Collaborators and Investigators

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

Sponsor

Huashan Hospital

Collaborators

Shanghai First Rehabilitation Hospital

Investigators

  • Principal Investigator: Xuehai Wu, Ph.D., Department of Neurosurgery, Huashan Hospital, Fudan University

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 (Actual)

April 21, 2025

Primary Completion (Estimated)

May 16, 2026

Study Completion (Estimated)

May 17, 2026

Study Registration Dates

First Submitted

March 3, 2025

First Submitted That Met QC Criteria

March 19, 2025

First Posted (Actual)

March 26, 2025

Study Record Updates

Last Update Posted (Actual)

December 16, 2025

Last Update Submitted That Met QC Criteria

December 8, 2025

Last Verified

March 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HY-TI2024-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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.

Clinical Trials on Disorder of Consciousness

Clinical Trials on TI Stimulation

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Tanzania

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe