Effectiveness of tTIs for Improving Consciousness in Patients With DoC
Effectiveness of Theta-Burst Patterned Temporal Interference Stimulation for Improving Awareness in Patients With Disorders of Consciousness: A Multicenter Randomized Double-Blind Controlled Trial
1 other identifier
interventional
136
1 country
1
Brief 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.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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for not_applicable
Started Mar 2026
Typical duration for not_applicable
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
March 8, 2026
CompletedFirst Submitted
Initial submission to the registry
March 18, 2026
CompletedFirst Posted
Study publicly available on registry
April 20, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
May 31, 2028
April 20, 2026
March 1, 2026
1.8 years
March 18, 2026
April 13, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (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.
Baseline and within 24 hours after the completion of the 5-day intervention.
Secondary Outcomes (5)
Change from Baseline Resting-State EEG
Baseline and within 24 hours after the completion of the 5-day intervention.
Change from Baseline TMS-EEG
Baseline and within 24 hours after the completion of the 5-day intervention.
Change from Baseline in Mismatch Negativity (MMN) Amplitude
Baseline and within 24 hours after the completion of the 5-day intervention.
Change from Baseline in P3a Amplitude
Baseline and within 24 hours after the completion of the 5-day intervention.
Long-term Changes in Coma Recovery Scale-Revised (CRS-R) Total Score
Baseline, and at 1 month, 3 months, and 6 months after the completion of the 5-day intervention.
Study Arms (2)
tTIs-Active Group
EXPERIMENTALParticipants 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).
tTIs-Control Group
SHAM 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).
Interventions
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.
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).
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Zhujiang Hospital of Southern Medical University
Guangzhou, Guangdong, 510280, China
Related Publications (3)
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PMID: 37872331BACKGROUNDGrossman 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.
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Related Links
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Qiuyou Xie
Zhujiang Hospital
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 18, 2026
First Posted
April 20, 2026
Study Start
March 8, 2026
Primary Completion (Estimated)
December 31, 2027
Study Completion (Estimated)
May 31, 2028
Last Updated
April 20, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will not share
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.