Exploring the Feasibility of Transcranial Ultrasound Stimulation in the Treatment of Schizophrenia

1. The purpose of this study is to evaluate the safety and feasibility of transcranial ultrasound stimulation (TUS) treatment in patients with schizophrenia. Subjects are individuals diagnosed with schizophrenia who will receive non-invasive, low-intensity pulsed ultrasound stimulation targeting the hippocampus and its surrounding regions. Evaluations will be conducted before and after the treatment sessions, including electrocardiograms (ECG), blood biochemistry tests, psychiatric symptom assessments, depression level assessments, and cognitive function assessments.
2. The primary objective is to assess the safety of this intervention in patients with schizophrenia. The secondary objective is to explore whether the current stimulation parameters may lead to improvements in the assessed symptoms. Ultimately, this study aims to support the future application of low-intensity pulsed ultrasound as a potential intervention to alleviate symptoms of schizophrenia and improve patients' quality of daily life.

Study Overview

• Status: Recruiting
• Conditions: Schizo Affective Disorder
• Intervention / Treatment: Device: Transcranial Ultrasound Stimulation; Device: Transcranial Ultrasound Stimulation

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yi-Ju Pan; Phone Number: +2168 886-2-8966-7000; Email: panyiju0211@gmail.com

Study Locations

• Taiwan
  • New Taipei City, Taiwan, 220
    • Recruiting
    • Far Eastern Memorial Hospital
    • Contact: Yi-Ju Pan, Ph. D.; Phone Number: 2168 886-2-8966-7000; Email: panyiju0211@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age: 18-65 years old.
2. Gender: Both males and females are eligible.
3. Diagnosed with schizophrenia according to DSM-V criteria (a PANSS total score of less than approximately 90).
4. No changes in medication (same dosage and same drug) for at least one month.

Exclusion Criteria:

1. History of head injury with loss of consciousness for more than 10 minutes or a history of brain surgery.
2. Any history of epilepsy.
3. Presence of a family history of epilepsy
4. Heavy alcohol consumption or use of illicit drugs (substance dependence within the last 6 months or substance abuse within the last month).
5. Any significant medical conditions that could affect normal brain function (including but not limited to stroke, CNS infections or tumors, or other major neurological diseases).
6. Presence of a cardiac pacemaker, implanted medication pump, intracardiac lines, or acute/unstable cardiac disease, as well as intracranial implants (e.g., aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metallic objects in or near the head (excluding oral metal objects)
7. Pregnant or breastfeeding women.
8. Presence of suicidal or self-harming tendencies
9. Current use of medications known to lower the seizure threshold or increase the risk of suicidal behavior
10. Presence of severe and uncontrolled systemic diseases (e.g., heart failure, liver failure, renal failure, vitamin B12 deficiency, hypothyroidism), as determined by the investigator to be unsuitable for study participation
11. Patients with uncontrolled diabetic retinopathy accompanied by active fundus hemorrhage
12. Concurrent participation in other clinical studies or clinical trials
13. Presence of contraindications to the medical devices used in this study (including pulsed ultrasound, EEG, and CT), such as unheindividuals with obvious head trauma, unhealed head surgery, or significant physical or psychiatric symptoms.
14. Any other conditions deemed unsuitable for participation in the clinical trial as assessed by the physician.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment	Device: Transcranial Ultrasound Stimulation; Actual treatment in this group; Device: Transcranial Ultrasound Stimulation; No actual treatment in this group
Placebo Comparator: pseudotreatment	Device: Transcranial Ultrasound Stimulation; Actual treatment in this group; Device: Transcranial Ultrasound Stimulation; No actual treatment in this group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Screening phase (4 weeks before the initiation of treatment) in serum concentrations of BDNF at 5(+4) Weeks.		Screening phase (4 weeks before the initiation of treatment) and Week 5(+4 weeks)
Change from Screening phase (4 weeks before the initiation of treatment) in serum concentrations of IL-1 at 5(+4) Weeks.		Screening phase (4 weeks before the initiation of treatment) and Week 5(+4 weeks)
Change from Screening phase (4 weeks before the initiation of treatment) in serum concentrations of IL-6 at 5(+4) Weeks.		Screening phase (4 weeks before the initiation of treatment) and Week 5(+4 weeks)
Change from Screening phase (4 weeks before the initiation of treatment) in serum concentrations of IL-8 at 5(+4) Weeks.		Screening phase (4 weeks before the initiation of treatment) and Week 5(+4 weeks)
Change from Screening phase (4 weeks before the initiation of treatment) in serum concentrations of TNF-alpha at 5(+4) Weeks.		Screening phase (4 weeks before the initiation of treatment) and Week 5(+4 weeks)
Status of neurological examination	Normal or Abnormal	baseline establishment, and Week 5(+4 weeks)
Height in centimeters		Screening phase (4 weeks before the initiation of treatment), and Week 5(+4 weeks)
Weight in kilograms		Screening phase (4 weeks before the initiation of treatment) and Week 5(+4 weeks)
Temperature in Celsius		Screening phase (4 weeks before the initiation of treatment) and Week 5(+4 weeks)
Respiratory rate in breaths per minutes		Screening phase (4 weeks before the initiation of treatment) and Week 5(+4 weeks)
Blood pressure in mmHg		Screening phase (4 weeks before the initiation of treatment) and Week 5(+4 weeks)
Electrocardiogram (ECG) R-R interval		Screening phase (4 weeks before the initiation of treatment) and Week 5(+4 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Positive and Negative Syndrome Scale (PANSS)	The Positive and Negative Syndrome Scale (PANSS), developed by Kay et al. in 1987, is a well-established clinical scale utilized to assess symptoms in patients with schizophrenia. The PANSS comprises 30 items categorized into three primary subscales: Positive Scale (7 items): Evaluates pathologically amplified symptoms, such as delusions and hallucinations. Negative Scale (7 items): Focuses on deficit symptoms, including blunted affect and social withdrawal. General Psychopathology Scale (16 items): Covers non-specific psychological states, such as anxiety and tension. Scoring and Clinical Application: Each item is scored on a 7-point severity scale ranging from 1 (absent) to 7 (extreme), yielding a total score between 30 and 210. Characterized by high reliability and validity, the PANSS serves as a critical tool in both clinical research and practice for measuring symptom severity, tracking therapeutic efficacy, and evaluating disease progression.	baseline establishment, Week 5(+4 weeks), Week 9(+4 weeks), Week 13(+4 weeks)
Clinical Global Impression (CGI)	The Clinical Global Impressions (CGI) scale is a brief, widely accepted instrument used by clinicians to rapidly evaluate psychiatric patients' symptom severity, therapeutic response, and overall efficacy based on direct observation and clinical experience. It comprises three companion subscales: CGI-Severity (CGI-S): Rates the clinician's impression of current illness severity on a 7-point scale, ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). CGI-Improvement (CGI-I): Evaluates overall change relative to the baseline state on a 7-point scale, from 1 (very much improved), 4 (no change), to 7 (very much worse). CGI-Efficacy (CGI-E): Indexes both therapeutic efficacy and treatment-related side effects to gauge global clinical benefit. Due to its simplicity and independence from complex instruments, the CGI is frequently employed in clinical trials and routine practice.	baseline establishment, Week 5(+4 weeks), Week 9(+4 weeks), Week 13(+4 weeks)
Hamilton Depression Rating Scale (HAMD)	The Hamilton Depression Rating Scale (HAMD), designed by Hamilton in 1960, is a clinical scale used to assess symptom severity in patients with depression. The most widely used version contains 17 items (HAMD-17). Each item is scored 0-4 or 0-2 based on severity. The HAMD-17 ranges from 0 to 52. The HAMD evaluates multiple dimensions, including mood, insomnia, appetite, anxiety, somatic symptoms, and daily functioning. Specific areas assessed include depressed mood, guilt, suicidal ideation, and changes in weight. Total scores indicate illness severity: scores below 7 are generally considered normal, while scores of 20 or higher indicate moderate-to-severe depression. Characterized by high reliability and validity, the HAMD serves as a gold-standard instrument for evaluating the efficacy of antidepressant therapies in clinical trials.	baseline establishment, Week 5(+4 weeks), Week 9(+4 weeks), Week 13(+4 weeks)
Cambridge Neuropsychological Test Automated Battery (CANTAB)	The following specific subtests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) will be administered, and individual scores for each task will be systematically recorded: Emotion Recognition Task (ERT): Measures social cognition and emotional processing. Multitasking Test (MTT): Evaluates executive function and cognitive flexibility. One Touch Stockings of Cambridge (OTS): Assesses spatial planning and problem-solving. Paired Associates Learning (PAL): Evaluates visual episodic memory and learning. Reaction Time (RTI): Measures motor and mental response speeds. Rapid Visual Information Processing (RVP): Assesses sustained attention. Spatial Working Memory (SWM): Evaluates working memory and strategy. Verbal Recognition Memory (VRM): Measures immediate and delayed verbal memory.	baseline establishment, Week 5(+4 weeks), Week 9(+4 weeks), Week 13(+4 weeks)

Collaborators and Investigators

• Sponsor: Far Eastern Memorial Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2025
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: May 14, 2026
• First Submitted That Met QC Criteria: May 27, 2026
• First Posted (Actual): June 2, 2026

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: May 27, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: LIPUS; TUS; scizophrenia
• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Psychotic Disorders
• Other Study ID Numbers: 114029-F

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No