Efficacy and Safety of Temporal Interference Stimulation in Treatment-Resistant Schizophrenia: An Exploratory Study.

August 16, 2026 updated by: Zhimin Wang

This exploratory study aims to evaluate the preliminary efficacy and safety of temporal interference (TI) stimulation in patients with treatment-resistant schizophrenia (TRS). TI is a noninvasive brain stimulation technique that uses two high-frequency electrical currents with slightly different frequencies to generate a lower-frequency modulation at a targeted deep brain region.

A total of 20 patients with TRS will receive 130-Hz TI stimulation targeting the anterior limb of the internal capsule (ALIC). Stimulation will be delivered at a total current intensity of 4 mA for 5 consecutive days, with four 40-minute sessions per day. Participants will continue their stable antipsychotic medication regimen during the study.

Clinical symptoms, cognitive function, social functioning, and safety will be assessed before treatment, after completion of the 5-day treatment course, and at a 2-week follow-up. The primary clinical outcome is the change in the Positive and Negative Syndrome Scale (PANSS) total score. Secondary assessments include PANSS subscale scores, the MATRICS Consensus Cognitive Battery (MCCB), Calgary Depression Scale for Schizophrenia (CDSS), Personal and Social Performance Scale (PSP), and Clinical Global Impression (CGI). Safety will be evaluated through daily monitoring of treatment-related discomfort and adverse events.

Magnetic resonance imaging (MRI) will also be performed before and after treatment to explore treatment-related changes in brain structure, functional activity, functional connectivity, activation, and cerebral blood flow. The study hypothesizes that TI stimulation targeting the ALIC may improve clinical symptoms in patients with TRS and may be associated with measurable changes in neuroimaging markers.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

20

Phase

  • Not Applicable

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:

  1. Right-handed male or female participants aged 18 to 65 years, inclusive.
  2. Diagnosis of schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), established by a psychiatrist at the attending-physician level or above and confirmed by the Mini International Neuropsychiatric Interview, version 7.0.2 (MINI 7.0.2).
  3. Inadequate response to sequential treatment with at least two antipsychotic medications of different chemical classes, each administered at an adequate dose (≥600 mg/day chlorpromazine equivalents) for an adequate duration (≥6 consecutive weeks at a therapeutic dose).
  4. Stable dose of antipsychotic medication for at least 4 weeks before enrollment.
  5. A score of 4 (moderate) or higher on at least two of the following Positive and Negative Syndrome Scale (PANSS) items: delusions, hallucinatory behavior, suspiciousness/persecution, or unusual thought content.
  6. Ability to understand the study procedures, willingness to participate voluntarily and comply with the study procedures, and provision of written informed consent.

Exclusion Criteria:

  1. Current diagnosis of another major psychiatric disorder other than schizophrenia that, in the investigator's judgment, may confound the diagnosis of schizophrenia or interfere with the assessment of treatment efficacy or safety.
  2. Receipt of other neuromodulation treatments, including modified electroconvulsive therapy (MECT), repetitive transcranial magnetic stimulation (rTMS), or transcranial direct current stimulation (tDCS), within the previous 3 months, or previous participation in an interventional clinical trial involving vagus nerve stimulation (VNS) or deep brain stimulation (DBS).
  3. A score ≥3 on Item 3 (suicide) of the 17-item Hamilton Depression Rating Scale (HAMD-17), or a score >3 on any of the following PANSS items: P4 Excitement, G14 Poor Impulse Control, P7 Hostility, or G8 Uncooperativeness.
  4. Contraindications to magnetic resonance imaging (MRI), including intracranial metallic implants, implanted cardiac pacemakers, or cochlear implants.
  5. Skull defects or fissures, or inability to tolerate stimulation-related adverse effects.
  6. Treatment-resistant epilepsy or other serious medical conditions that, in the investigator's judgment, may potentially affect treatment or participation in the study.
  7. Pregnancy.
  8. Any other condition that, in the investigator's judgment, makes the participant unsuitable for participation in the study.

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Temporal Interference Stimulation
Device: Temporal Interference Stimulation
Participants with treatment-resistant schizophrenia will receive 130-Hz temporal interference stimulation targeting the anterior limb of the internal capsule (ALIC). Stimulation will be delivered at a total current intensity of 4 mA for 5 consecutive days, with four 40-minute sessions per day and a 20-minute interval between sessions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at the End of Treatment
Time Frame: Baseline to Day 5
Baseline to Day 5
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at 2-Week Follow-up
Time Frame: Baseline to Day 14 ± 2 days after treatment completion
Baseline to Day 14 ± 2 days after treatment completion

Secondary Outcome Measures

Outcome Measure
Time Frame
Change From Baseline in PANSS Positive Symptom Subscale Score
Time Frame: Baseline to Day 5 and Day 14 ± 2 days after treatment completion
Baseline to Day 5 and Day 14 ± 2 days after treatment completion
Change From Baseline in PANSS Negative Symptom Subscale Score
Time Frame: Baseline to Day 5 and Day 14 ± 2 days after treatment completion
Baseline to Day 5 and Day 14 ± 2 days after treatment completion
Change From Baseline in PANSS General Psychopathology Subscale Score
Time Frame: Baseline to Day 5 and Day 14 ± 2 days after treatment completion
Baseline to Day 5 and Day 14 ± 2 days after treatment completion
Change From Baseline in MATRICS Consensus Cognitive Battery (MCCB) Score
Time Frame: Baseline to Day 5 and Day 14 ± 2 days after treatment completion
Baseline to Day 5 and Day 14 ± 2 days after treatment completion
Change From Baseline in Calgary Depression Scale for Schizophrenia (CDSS) Score
Time Frame: Baseline to Day 5 and Day 14 ± 2 days after treatment completion
Baseline to Day 5 and Day 14 ± 2 days after treatment completion
Change From Baseline in Personal and Social Performance Scale (PSP) Score
Time Frame: Baseline to Day 5 and Day 14 ± 2 days after treatment completion
Baseline to Day 5 and Day 14 ± 2 days after treatment completion
Change From Baseline in Clinical Global Impression (CGI) Score
Time Frame: Baseline to Day 5 and Day 14 ± 2 days after treatment completion
Baseline to Day 5 and Day 14 ± 2 days after treatment completion

Collaborators and Investigators

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

Sponsor

Zhimin Wang

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 (Estimated)

August 1, 2026

Primary Completion (Estimated)

May 1, 2027

Study Completion (Estimated)

July 1, 2027

Study Registration Dates

First Submitted

August 16, 2026

First Submitted That Met QC Criteria

August 16, 2026

First Posted (Actual)

August 19, 2026

Study Record Updates

Last Update Posted (Actual)

August 19, 2026

Last Update Submitted That Met QC Criteria

August 16, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CapitalMedicalU

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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.

Subscribe