Effectiveness of tTIs for Improving Consciousness in Patients With DoC
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18-70
SponsorZhujiang Hospital
About this 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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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.
Trial design
Design model
Parallel
Treatments tested in this trial
Theta-burst Patterned Temporal Interference Stimulation (tTIs)
DeviceThe 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 Stimulation
DeviceThe 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).
Treatment groups
136 Participants
are divided into 2 treatment groupsGroup A: tTIs-Active GroupExperimental treatment 1 intervention
Group B: tTIs-Control GroupSham comparator 1 intervention
Trial outcomes
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.
Time frame
Baseline and within 24 hours after the completion of the 5-day intervention.Secondary outcomes
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.
Time frame
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).
Time frame
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.
Time frame
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.
Time frame
Baseline and within 24 hours after the completion of the 5-day intervention.Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Source ClinicalTrials.gov