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Disorders of ConsciousnessNCT07539740

Effectiveness of tTIs for Improving Consciousness in Patients With DoC

A study testing Theta-burst Patterned Temporal Interference Stimulation (tTIs) in people with Disorders of Consciousness and Vegetative State, run by Zhujiang Hospital at 1 site in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

The goal of this clinical trial is to learn if a new type of brain stimulation called theta-burst patterned temporal interference stimulation (tTIs) works to improve awareness in people with disorders of consciousness (DoC). The main questions it aims to answer are: 1. Read more about this study

Who is it for?
Ages 18 to 70 years
What is being tested?
Theta-burst Patterned Temporal Interference Stimulation (tTIs)
Type of treatment
Medical device
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
136 participants
Where
1 siteChina
Study dates
8 Mar 2026to 31 May 2028
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age: 18 to 70 years old.
  • Condition: Patients diagnosed with Disorders of Consciousness (DoC), including Vegetative State (VS)/Unresponsive Wakefulness Syndrome (UWS) or Minimally Conscious State (MCS) according to international guidelines.
  • Duration: Disease course ≤ 1 year.Medical History: No history of neuro-psychiatric disorders prior to the brain injury.
  • Handedness: Right-handed.Safety: No contraindications for tTIs, EEG, or MRI.
  • Medication: Not currently using sedative drugs or medications that interfere with brain stimulation, such as Na2+ or Ca2+ channel blockers, or NMDA receptor antagonists.

Who cannot join

  • Concurrent Trials: Participation in other non-invasive or invasive neuromodulation trials.
  • Epilepsy: Uncontrolled epilepsy, defined as a seizure within 4 weeks prior to enrollment.
  • Implants: Presence of metal implants in the skull, brain pacemakers, or implanted brain devices (e.g., spinal cord stimulator).
  • Structural Issues: Skull defects at the site of stimulation that prevent the implementation of tTIs.
  • Systemic Implants: Presence of systemic metal implants, such as cardiac pacemakers.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

China1 site, 1 recruiting
  • Zhujiang Hospital of Southern Medical University

    Guangzhou, Guangdong, 510280

    Chengwei Xu, 86+13450457096, xuchweii@163.com

    Shiying Zhuang, 86+13505085958, 13505085958@163.com

    Recruiting

Other trials in China

About this study

Official title: Effectiveness of Theta-Burst Patterned Temporal Interference Stimulation for Improving Awareness in Patients With Disorders of Consciousness: A Multicenter Randomized Double-Blind Controlled Trial

The goal of this clinical trial is to learn if a new type of brain stimulation called theta-burst patterned temporal interference stimulation (tTIs) works to improve awareness in people with disorders of consciousness (DoC). The main questions it aims to answer are:

  1. Does tTIs help people with disorders of consciousness show more signs of awareness?
  2. Does tTIs improve the brain's ability to process information and connect different brain areas? Is tTIs safe and easy for people with disorders of consciousness to tolerate? Researchers will compare a group receiving active tTIs to a group receiving a "sham" stimulation (a look-alike stimulation that delivers no real current) to see if the real stimulation works better.

Participants will:Receive either active tTIs or sham stimulation twice a day for 5 consecutive days (total of 10 sessions). Undergo brain activity tests (EEG) and physical exams to check their level of awareness before and after the 5 days of treatment. Have their progress followed by researchers through phone calls at 1, 3, and 6 months after the treatment ends.

Read the detailed description
  1. Study Overview and Mechanism This study is a multicenter, randomized, double-blind, sham-controlled clinical trial designed to evaluate the efficacy of theta-burst patterned temporal interference stimulation (tTIs) in patients with disorders of consciousness (DoC). The intervention targets the centromedian-parafascicular nuclei complex (CM-pf) of the thalamus, a critical hub for maintaining and modulating consciousness. By utilizing high-frequency carrier waves (>1 kHz), tTIs creates a low-frequency interference field at the deep target without directly activating the superficial cortex, thereby improving spatial selectivity and patient comfort.
  2. Intervention Protocol (Revised 5-Day Course) Participants will be randomly assigned to either the tTIs-active group or the tTIs-control group (1:1 ratio). (1) Active Group: Participants will receive tTIs with a 100 Hz pulse burst repeated at a 5 Hz (theta) rhythm. Stimulation will be administered for 30 minutes per session, twice daily, for 5 consecutive days (totaling 10 sessions). The current intensity is set at 2 mA per channel (total 4 mA). (2) Control (Sham) Group: Participants will receive sham stimulation using the same device setup, but the current will be set to 0 mA after a brief initial ramp-up to simulate the sensation.
  3. Assessment and Monitoring Individualized MRI-based navigation will be used for precise targeting of the CM-pf complex. Awareness levels will be assessed using the Coma Recovery Scale-Revised (CRS-R) at baseline and within 24 hours after the completion of the 5-day intervention. Neurophysiological changes will be monitored via high-density EEG (ABCD typing), TMS-EEG (Perturbational Complexity Index, PCI), and Event-Related Potentials (MMN and P3a).
  4. Follow-up and Safety Safety and tolerability will be monitored throughout the treatment. Long-term behavioral changes will be followed via telephone at 1, 3, and 6 months post-intervention to record CRS-R score variations

Note on Study Duration: The attached protocol (PDF) is the currently institutional-approved version specifying a 10-day course. However, an ethics amendment is currently being processed to optimize the intervention to a 5-day course (10 sessions total) as reflected in this registration. All study procedures will follow the updated 5-day plan once the formal amendment letter is issued.

Being tested
Theta-burst Patterned Temporal Interference Stimulation (tTIs), Sham Temporal Interference Stimulation
Keywords
Temporal Interference Stimulation (tTIs), Theta-burst Patterned Stimulation, Deep Brain Stimulation (Non-invasive), Thalamic Stimulation, Centromedian-parafascicular Nuclei (CM-pf), Perturbational Complexity Index (PCI), Coma Recovery Scale-Revised (CRS-R)
Medical subject headings
Consciousness Disorders, Persistent Vegetative State

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Theta-burst Patterned Temporal Interference Stimulation (tTIs)Device

    Also called Respiratory-burst tTIs, TBS-tTIs, Non-invasive Deep Brain Stimulation

    The intervention targets the CM-pf complex using two pairs of high-frequency electrodes. Carrier frequency f1 = 2 kHz and f2 = 2.1 kHz to generate a 100 Hz interference. The stimulation is delivered in theta-burst patterns (3-pulse bursts at 100 Hz, repeated at 5 Hz). Sessions last 30 minutes, administered twice daily for 5 consecutive days (totaling 10 sessions). Current intensity is 2 mA per channel.

  • Sham Temporal Interference StimulationDevice

    The sham group uses the same device and electrode configuration as the active group. The device delivers 0 mA current after a 30-second ramp-up to mimic skin sensation. Sessions last 30 minutes, administered twice daily for 5 consecutive days (totaling 10 sessions).

Study groups in NCT07539740
Study groupRoleWhat they receive
tTIs-Active GroupExperimentalParticipants will receive active theta-burst patterned temporal interference stimulation (tTIs) targeting the centromedian-parafascicular nuclei complex (CM-pf). The stimulation consists of 3-pulse bursts at 100 Hz, repeated at a 5 Hz (theta) rhythm. Treatment will be administered for 30 minutes per session, twice daily, for 5 consecutive days (totaling 10 sessions). The current intensity is 2 mA per channel (total 4 mA).
Receives: Device: Theta-burst Patterned Temporal Interference Stimulation (tTIs)
tTIs-Control GroupSham comparatorParticipants will receive sham stimulation using the same device and electrode placement as the active group. The device will deliver 0 mA current after a brief initial ramp-up period to mimic the skin sensation. The procedure lasts 30 minutes per session, twice daily, for 5 consecutive days (totaling 10 sessions).
Receives: Device: Sham Temporal Interference Stimulation

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in Coma Recovery Scale-Revised (CRS-R) Total Score

    The Coma Recovery Scale-Revised(CRS-R), a total of 23 points, is widely used to define the level of consciousness and assess neurobehavioral recovery of patients with DOC. It is based on six subscales that assess auditory(4 points), visual(5 points), motor(6 points), motor/speech(3 points), communication(2 points), and arousal processes(3 points). Each item of CRS-R is in good agreement with the diagnostic and differential diagnostic criteria of VS/UWS, MCS and EMCS. The higher scores mean a better outcome.

    Measured: Baseline and within 24 hours after the completion of the 5-day intervention.

Secondary outcomes (5)
  1. Change from Baseline Resting-State EEG

    Based on the assumption that specific cortical oscillations indicate varying levels of thalamocortical integrity that has defined four dynamic regimes that build on the mesocircuit model, each detectable with EEG and corresponding to a thalamo cortical state that indicates progressive circuit recovery.These EEG types are labeled A-D (hence, ABCD model) .Later types (C, D) denote more progressive recovery (i.e., are "better") than earlier types, (A, B), which correspond to a quiescent thalamic state.

    Measured: Baseline and within 24 hours after the completion of the 5-day intervention.

  2. Change from Baseline TMS-EEG

    Transcranial magnetic stimulation combined with electroencephalography (TMS-EEG) is an effective way to measure cortical activity..In this study, PCIst, a derivative version of PCI, PCIst was chosen as an alternative, which estimates the complexity of TMS perturbations by signal decomposition and recurrence quantification analysis (RQA).

    Measured: Baseline and within 24 hours after the completion of the 5-day intervention.

  3. Change from Baseline in Mismatch Negativity (MMN) Amplitude

    MMN is an event-related potential (ERP) reflecting the brain's automatic processing of auditory information. The amplitude is measured in microvolts (μV). According to clinical standards, a more negative MMN amplitude (e.g., from -0.5 μV to -1.5 μV ) indicates better pre-attentive sensory processing.

    Measured: Baseline and within 24 hours after the completion of the 5-day intervention.

  4. Change from Baseline in P3a Amplitude

    P3a is an ERP reflecting the brain's automatic bottom-up orienting response to novel stimuli. The amplitude is measured in microvolts (μV). A higher positive amplitude indicates more efficient automatic attention-switching and improved cognitive processing.

    Measured: Baseline and within 24 hours after the completion of the 5-day intervention.

  5. Long-term Changes in Coma Recovery Scale-Revised (CRS-R) Total Score

    The Coma Recovery Scale-Revised(CRS-R), a total of 23 points, is widely used to define the level of consciousness and assess neurobehavioral recovery of patients with DOC. It is based on six subscales that assess auditory(4 points), visual(5 points), motor(6 points), motor/speech(3 points), communication(2 points), and arousal processes(3 points). Each item of CRS-R is in good agreement with the diagnostic and differential diagnostic criteria of VS/UWS, MCS and EMCS. The higher scores mean a better outcome.

    Measured: Baseline, and at 1 month, 3 months, and 6 months after the completion of the 5-day intervention.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Apr 2026
  2. Study start8 Mar 2026
  3. Primary completion31 Dec 2027 (estimated)
  4. Study completion31 May 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
This is a multicenter, randomized, double-blind, sham-controlled parallel-group trial. Participants are randomly assigned to either the tTIs-active group or the tTIs-control group in a 1:1 ratio.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
136 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07539740
Sponsor's protocol ID
L20260312
Status last verified
Mar 2026
First submitted
18 Mar 2026
Last updated
20 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: The raw neurophysiological data (EEG) collected in this study are classified as human genetic resources under national regulations. To ensure participant privacy and data security, the individual participant data (IPD) will not be shared with outside researchers.

Publications

  • Yasuno T, Okamoto H, Nagai M, Kimura S, Yamamoto T, Nagano K, Furubayashi T, Yoshikawa Y, Yasui H, Katsumi H, Sakane T, Yamamoto A. In vitro study on the transport of zinc across intestinal epithelial cells using Caco-2 monolayers and isolated rat intestinal membranes. Biol Pharm Bull. 2012;35(4):588-93. doi: 10.1248/bpb.35.588.

    PubMed 22466565
  • Wei H, Zhang L, Wang Z. Four antibiotics and copper interactive effects on the growth and physiological characteristics of Hydrilla verticillata (L.f.) Royle. Environ Sci Pollut Res Int. 2023 Nov;30(55):117531-117544. doi: 10.1007/s11356-023-30415-w. Epub 2023 Oct 23.

    PubMed 37872331
  • Grossman N, Bono D, Dedic N, Kodandaramaiah SB, Rudenko A, Suk HJ, Cassara AM, Neufeld E, Kuster N, Tsai LH, Pascual-Leone A, Boyden ES. Noninvasive Deep Brain Stimulation via Temporally Interfering Electric Fields. Cell. 2017 Jun 1;169(6):1029-1041.e16. doi: 10.1016/j.cell.2017.05.024.

    PubMed 28575667

Questions about this trial

What is this clinical trial studying?

A study testing Theta-burst Patterned Temporal Interference Stimulation (tTIs) in people with Disorders of Consciousness and Vegetative State, run by Zhujiang Hospital at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 20 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Chengwei Xu (86+13450457096, xuchweii@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Coma Recovery Scale-Revised (CRS-R) Total Score (time frame: Baseline and within 24 hours after the completion of the 5-day intervention.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07539740, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Apr 2026.

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