Not yet recruitingNCT07927790ClinicalTrials.gov record

Temporal Interference Stimulation Targeting Thalamus for Schizophrenia-Related Cognitive Dysfunction

Schizophrenia Disorder · Cognitive Impairments

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THE QUICK READ

What this study involves

The registry does not currently label this study as recruiting. Ask about its status before planning a screening visit.

Study type: Interventional
Phase: Not applicable
Age range: 18 years - 60 years
Sex eligible: All sexes
Healthy volunteers: Not accepted
Participants: 80 Estimated

These are starting points, not an eligibility decision. The research team must review the full requirements.

About the research

Prefrontal cortical dysfunction in patients with schizophrenia (SCZ) may result from impaired thalamic inputs to this region. Meanwhile, patients with SCZ exhibit a reduced GABA/glutamate ratio in the thalamus, indicating thalamic excitation/inhibition (E/I) imbalance. In addition, SCZ patients show marked reduction of sleep spindles, which are predominantly generated by the thalamic reticular nucleus. Therefore, thalamus-targeted temporal interference stimulation (TIS) may modulate the function of thalamocortical circuits, ameliorate clinical symptoms including cognitive deficits in patients with SCZ, and serve as an effective non-pharmacological intervention. This study consists of two trial components with three objectives: (1) to explore the therapeutic effect of TIS on cognitive function in patients with SCZ; (2) to explore the effect of TIS on positive symptoms in patients with SCZ; (3) to investigate the neural mechanisms underlying TIS-mediated symptom modulation in SCZ.

Trial 1: This study adopts a randomized, controlled, crossover design. Participants will be randomly assigned to two groups: Group A and Group B. Clinical data from 30 patients with schizophrenia (15 participants per group) will be collected, including baseline clinical rating scale scores, cognitive assessments, electroencephalography (EEG), and magnetic resonance imaging (MRI) data. All participants will receive two sessions of TIS intervention in a crossover fashion, with a 1-week washout period between the two interventions. One day prior to each TIS session, participants will complete two training runs of the Sternberg Item-Recognition Paradigm (SIRP) to eliminate confounding learning effects. Outcome measurements including clinical scale scores, cognitive assessments, EEG and MRI data will be acquired at baseline. Task-state MRI will be recorded during both stimulation sessions.

Trial 2: This trial uses a rigorous randomized controlled design. Participants will be randomized into two arms: the TIS group and the control group. Fifty patients with schizophrenia will be enrolled (25 participants per group). Baseline data will be collected, including clinical symptom ratings, cognitive function scores, EEG-derived E/I imbalance metrics, and MRI data. The intervention lasts for 2 weeks with twice-daily stimulation, totaling 20 sessions. Assessments will be performed at baseline, at the end of the 2-week intervention, and at a 4-week post-intervention follow-up to evaluate changes in clinical symptoms, cognition, EEG E/I imbalance, and brain structural and functional features. This trial aims to explore the short-term efficacy, safety, and neurobiological mechanisms of TIS for improving cognitive function in schizophrenia.

Who may be able to participate?

The list below is the sponsor’s full registry wording. It can include conditions, prior treatment, test results and other requirements. A match in search does not mean you qualify.

Inclusion Criteria:

18 to 60 years of age
meet the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for schizophrenia as confirmed by the \*Structured Clinical Interview for DSM-5\* (SCID-5)
receiving 1 or 2 antipsychotic medications at a stable dose for at least 1 week before enrollment. Concurrent use of mood stabilizers, antidepressants, or excessive benzodiazepines (lorazepam \>2 mg/day) was prohibited，During treatment, the types of antipsychotic drugs remain the same, and the dosage adjustments should not exceed 25%.
have functional impairment in daily activities
provide written informed consent
the disease duration does not exceed 8 years
The Global Deficit Score (GDS) for the MATRICS Consensus Cognitive Battery (MCCB) reaches 0.5 or above
At least one item of the Positive and Negative Syndrome Scale (PANSS) positive subscale has a score ≥ 4.

Exclusion Criteria:

comorbid psychiatric disorders, intellectual disability, clinically significant mood symptoms, or substance use disorders (except caffeine or tobacco)
a history of seizures, meningitis, or encephalitis
contraindications to transcranial electrical stimulation
intracranial tumors or prior neurosurgery
a history of severe head trauma
receipt of other transcranial electrical or magnetic therapies within 1 month before enrollment
with clear drug-induced extrapyramidal reaction

Understand screening

Treatment, groups and participation

The registry may describe treatments and study duration without a complete visit calendar. Ask the study team for the exact schedule, procedures, risks, costs and alternatives. Keep your usual care plan unless your treating clinician tells you otherwise.

Assignment: Random assignment
Masking: Triple masked

Group A (A/S): Active stimulation first, followed by sham stimulation

Group A receives active stimulation in the first session and sham stimulation in the second session.One day prior to each TIS session, participants complete two training runs of the Sternberg Item-Recognition Paradigm (SIRP) to eliminate confounding learning effects.Electrodes are placed according to the 10-10 EEG system and secured with conductive paste.Stimulation is individualized based on each participant's Individual Alpha Frequency (IAF). Resting-state EEG is recorded before stimulation to determine the IAF. A continuous high-frequency sinusoidal current pair with a base frequency of 2000 Hz and a beat frequency tuned to the IAF is delivered through each electrode to generate pulsed stimulation for individualized iTBS.Electric field modeling based on T1-weighted MRI images is used to optimize personalized electrode montages, ensuring an electric field strength ≥ 0.2 V/m within the left thalamus for each participant.

Device: temporal interference stimulation · Device: Sham TIS

Group B (S/A): Sham stimulation first, followed by active stimulation

Group B receives sham stimulation in the first session and active stimulation in the second session.One day prior to each TIS session, participants complete two training runs of the Sternberg Item-Recognition Paradigm (SIRP) to eliminate confounding learning effects. Electrodes are placed according to the 10-10 EEG system and secured with conductive paste.Stimulation is individualized based on each participant's Individual Alpha Frequency (IAF). Resting-state EEG is recorded before stimulation to determine the IAF. A continuous high-frequency sinusoidal current pair with a base frequency of 2000 Hz and a beat frequency tuned to the IAF is delivered through each electrode to generate pulsed stimulation for individualized iTBS.Electric field modeling based on T1-weighted MRI images is used to optimize personalized electrode montages, ensuring an electric field strength ≥ 0.2 V/m within the left thalamus for each participant.

Device: temporal interference stimulation · Device: Sham TIS

sham group:Sham TIS

Participants in the sham group receive sham TIS following the identical schedule: two sessions daily for 10 days, 20 sessions in total. The sham paradigm uses the same 2000 Hz current pair. Current is only delivered during the 10-second ramp-up and ramp-down phases at the start and end of each session, while no current is applied during the middle period. This setup mimics the scalp tingling sensation induced by current changes at the beginning and end of active stimulation. All other hardware, electrode placement and study procedures are identical to the active TIS group.

Device: Sham TIS

TIS group:TIS

Participants in the TIS group receive active TIS stimulation, with two intervention sessions per day for 10 consecutive days, totaling 20 sessions. Each session lasts 30 minutes. Electrodes are placed according to the 10-10 EEG system and secured with conductive paste. Stimulation is individualized based on each participant's Individual Alpha Frequency (IAF). Resting-state EEG is recorded before stimulation to determine the IAF. A continuous high-frequency sinusoidal current pair with a base frequency of 2000 Hz and a beat frequency tuned to the IAF is delivered through each electrode to generate pulsed stimulation for individualized iTBS. Electric field modeling based on T1-weighted MRI images is used to optimize personalized electrode montages, ensuring an electric field strength ≥ 0.2 V/m within the left thalamus for each participant. Each stimulation session lasts 30 minutes, with a 10-second ramp-up period at the onset and a 10-second ramp-down period at the end.

Device: temporal interference stimulation

temporal interference stimulation DEVICE

Thalamus-targeted temporal interference stimulation delivered via Dome Medical TES NEURO-800, individualized based on individual alpha frequency with electric field optimization from T1 MRI.

Sham TIS DEVICE

Sham temporal interference stimulation with identical setup; current only delivered during brief ramp-up/ramp-down periods to mimic scalp sensation without effective thalamic stimulation.

Prepare your questions

What researchers are measuring

Outcome measures describe what is being studied. They are not proof that a treatment works.

Primary measures

Changes in brain function

Time frame: baseline (T1 structural scan); pre-, during, and post-first stimulation (Day 1); pre-, during, and post-second stimulation (Day 9)

Functional MRI (fMRI) is based on the blood oxygen level dependent (BOLD) contrast that can detect changes in blood oxygenation to analyze the change of brain function after intervention.This outcome is for sub-trial 1 (single-session crossover TIS).

changes on the MATRICS Consensus Cognitive Battery (MCCB) scores

Time frame: baseline,2 week visit, 4-week follow-up visit

The MATRICS Consensus Cognitive Battery (MCCB) can be used for cognitive assessment of schizophrenia, bipolar disorder, and other neuropsychiatric diseases. The MCCB covers nine cognitive domains, including attention, information processing speed, verbal learning and memory, visual learning and memory, spatial working memory, reasoning, problem solving, social cognition, executive function, and fine motor skills. The working memory domain does not include verbal working memory because the Chinese language would not make feasible the inclusion of the LNS test.This outcome is for sub-trial 2 (2-week repeated TIS).

Secondary measures

Changes in Positive and Negative Symptom Scale-6 (PANSS-6) scores

Time frame: pre-and post-first stimulation (Day 1); pre- and post-second stimulation (Day 9)

The PANSS-6 is a shortened version of the Positive and Negative Syndrome Scale for assessment of psychotic symptoms in schizophrenia. Scores range from 6 to 42, higher score indicates more severe psychotic symptoms. This outcome is for sub-trial 1 (single-session crossover TIS).

Change in brain responses during the Sternberg Item-Recognition Paradigm (SIRP)

Time frame: pre-, during, and post-first stimulation (Day 1); pre-, during, and post-second stimulation (Day 9)

The Sternberg Item-Recognition Paradigm (SIRP) is a task fMRI paradigm for evaluating working memory processing. T1-weighted structural MRI at baseline is acquired for individual brain modeling. Task fMRI scans are obtained pre-stimulation, during stimulation, and post-stimulation for each session. This outcome is for sub-trial 1 (single-session crossover TIS).

Changes in brain function

Time frame: baseline, 2-week visit (end of intervention)

Change in PANSS total scores

Time frame: baseline, 2-week visit (end of intervention), 4-week follow-up visit

The Positive and Negative Syndrome Scale (PANSS) is widely used to assess positive, negative and general psychopathology symptoms of schizophrenia. Scores range from 30 to 210, higher score indicates more severe positive and negative symptoms. This outcome is for sub-trial 2 (2-week repeated TIS).

Change in PSYRATS scores

Time frame: baseline, 2-week visit (end of intervention), 4-week follow-up visit

The Psychotic Symptoms Rating Scale (PSYRATS) quantifies the severity and dimensional features of hallucinations and delusions in patients with psychosis. This outcome is for sub-trial 2 (2-week repeated TIS).

Change in SANS scores

Time frame: baseline, 2-week visit (end of intervention), 4-week follow-up visit

The Scale for the Assessment of Negative Symptoms (SANS) evaluates the severity of negative symptoms in schizophrenia, including affective flattening, alogia, avolition-apathy, anhedonia-asociality and attentional impairment. This outcome is for sub-trial 2 (2-week repeated TIS).

Change in GAF scores

Time frame: baseline, 2-week visit (end of intervention), 4-week follow-up visit

The Global Assessment of Functioning (GAF) scale rates overall psychological, social and occupational functioning. Scores range from 0 to 100, higher score represents better functional status. This outcome is for sub-trial 2 (2-week repeated TIS).

Change in Global Functioning Scale (GFS) scores

Time frame: baseline, 4-week follow-up visit

The Global Functioning Scale (GFS) assesses real-world social and role functioning among individuals with severe mental disorders. This outcome is for sub-trial 2 (2-week repeated TIS).

Change in Social Functioning Scale (SFS) scores

Time frame: baseline,4-week follow-up visit

The Social Functioning Scale (SFS) measures multiple domains of social functioning for patients with schizophrenia spectrum disorders. This outcome is for sub-trial 2 (2-week repeated TIS).

Change in brain responses during the 2-back task fMRI paradigm

Time frame: 2-week visit (end of intervention)

Task fMRI based on the 2-back working memory paradigm used to assess working memory-related thalamocortical brain activity. High-resolution T1-weighted structural MRI at baseline is acquired for individual brain modeling. This outcome is for sub-trial 2 (2-week repeated TIS).

Change in 1/f aperiodic EEG signal (E/I balance index)