Precise Intervention Technology and Application of Low Intensity TUS on Negative Symptoms of Schizophrenia

Precise Intervention Technology and Application of Low Intensity Transcranial Ultrasound Stimulation (TUS) on Negative Symptoms of Schizophrenia

Based on the current background and our previous studies, TUS has been proved that rTUS intervention could induce long-term potentiation like (LTP-like) plasticity and neuromodulate the brain cortex in schizophrenia patients. rTUS over the left dorsolateral prefrontal cortex (DLPFC) can alleviate the negative symptoms in schizophrenia. In this double-blind, randomized, sham-controlled study, the efficacy of different treatment options and mechanisms of low-intensity rTUS on negative symptoms will be investigated.

Study Overview

• Status: Recruiting
• Conditions: Negative Symptoms of Schizophrenia
• Intervention / Treatment: Device: low-intensity transcranial ultrasound stimulation (TUS)

Detailed Description

Negative symptoms is a core symptom of schizophrenia related to poor functional outcome which remains largely treatment refractory. Prior studies indicated that abnormalities in the prefrontal-temporal circuit and glutamate/GABA imbalances may be the root causes of negative symptoms. Transcranial ultrasound stimulation (TUS), an emerging non-invasive neuromodulation technique, can modulate neuroplasticity in the prefrontal and temporal cortex. In this double-blind, randomized, sham-controlled study, the efficacy of different treatment options and mechanisms of low-intensity rTUS on negative symptoms will be investigated. Schizophrenia inpatients with predominant negative symptoms will be recruited and randomly allocated into single-target group (left DLPFC), both-target group (both left DLPFC and right STG) or sham group in ratio of 1:1:1. This study aims to determine the efficacy of TUS and to reveal its underlying neural mechanism. MEPs, TEPs ,multi-modal MRI and rs-EEG will be detected. Neuropsychological assessments will also be conducted to develop the optimized treatment strategy. The study points to a novel and promising therapeutic neuromodulation approach that may improve the functional outcome of schizophrenia, which has been the main cause of mental disability.

• Study Type: Interventional
• Enrollment (Estimated): 81
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dengtang LIU; Phone Number: 021-34773434; Email: liudengtang@smhc.org.cn

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200030
      • Recruiting
      • Shanghai Mental Health Center
      • Contact: Dengtang LIU; Phone Number: 021-34773434; Email: liudengtang@smhc.org.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Meet the DSM-5 diagnostic criteria for schizophrenia or schizoaffective disorder;
• Age18-50, right-handed, Han nationality;
• Score of at least 1 item from N1 to N7 in PANSS is ≥4 (moderate or above);
• Be in a stable condition, received second-generation antipsychotics for at least 4 weeks or more;
• Written informed consent;

Exclusion Criteria:

• Current or past neurological illness, severe physical diseases, substance abuse or alcohol dependence, mental retardation, pregnant or lactation;
• Uncooperative or risky patients with high excitement, stupor, disorder of words and deeds, negative suicide, etc.;
• History of MECT or other physical therapy within 6 months;
• History of epilepsy, or epileptic waves on the baseline EEG;
• Ruled out share antiepileptic drugs, carbamazepine, valproic acid salt) or larger doses of benzodiazepines drugs (> 10 mg/day, diazepam clonazepam 2 mg/day, 1 mg/day, alprazolam lorazepam 2 mg/day, midazolam 10 mg/day, 20 mg/day, Mr Shah diazepam triazolam 0.5 mg/day), avoid the use of chlorine drug, (in principle, to avoid the use of antiepileptic drugs and clonazepam;Other antipsychotic drugs, if necessary, remain unchanged during the course of treatment;
• Contraindications to TUS and MRI are present.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: single-target group (left DLPFC); 27 eligible patients will be treated with active TUS for 4 weeks on the left DLPFC	Device: low-intensity transcranial ultrasound stimulation (TUS); The rTUS was administered using an immersion-type focused ultrasound transducer (V391-SU, Olympus NDT, Waltham, USA). Low-intensity transcranial ultrasound stimulation on the target. Duration:20 days (workdays for four consecutive weeks).
Active Comparator: both-target group (both left DLPFC and right STG); 27 eligible patients will be treated with active TUS for 4 weeks on the both left DLPFC and right STG	Device: low-intensity transcranial ultrasound stimulation (TUS); The rTUS was administered using an immersion-type focused ultrasound transducer (V391-SU, Olympus NDT, Waltham, USA). Low-intensity transcranial ultrasound stimulation on the target. Duration:20 days (workdays for four consecutive weeks).
Sham Comparator: sham group; 27 eligible patients will be treated with sham TUS for 4 weeks on the left DLPFC and right STG, respectively.	Device: low-intensity transcranial ultrasound stimulation (TUS); The rTUS was administered using an immersion-type focused ultrasound transducer (V391-SU, Olympus NDT, Waltham, USA). Low-intensity transcranial ultrasound stimulation on the target. Duration:20 days (workdays for four consecutive weeks).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in the Scale for Assessment of Negative Symptoms(SANS)	Change from baseline in the Scale for Assessment of Negative Symptoms(SANS) at 4 weeks and 8 weeks. The minimum to maximum value is 0-120. Lower scores mean a better outcome.	baseline, 4 weeks and 8 weeks
Change from baseline in Positive and Negative Syndrome Scale(PANSS)	Change from baseline in Positive and Negative Syndrome Scale(PANSS) at 4 weeks and 8 weeks. The minimum to maximum value is 30-210. Lower scores mean a better outcome.	baseline, 4 weeks and 8 weeks
Change from baseline in the Brief Negative Symptom Scale (BNSS)	Change from baseline in the Brief Negative Symptom Scale (BNSS) at 4 weeks and 8 weeks. The minimum to maximum value is 0-78. Lower scores mean a better outcome.	baseline, 4 weeks and 8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of Multi-modal Brain Neuroimaging in structure	Brain structure data will be acquired.	baseline and 4 weeks
Change of Multi-modal Brain Neuroimaging in resting- state fMRI	Resting-state fMRI data will be acquired.	baseline and 4 weeks
Change of Multi-modal Brain Neuroimaging in 1H-MRS	1H-MRS data will be acquired.	baseline and 4 weeks
Change of cognitive Function	Change from baseline in MATRICS MCCB	baseline, 4 weeks and 8 weeks
Change of EEG microstates	EEG microstates propose that resting-state neural activity is characterized by several globally functional states with specific spatial distributions at sub-second temporal scales. In this study, resting-state 64-channel EEG data were collected from participants before and after rTUS treatment (at baseline and 4 weeks). The aim was to investigate the effects of rTUS on seven types of EEG microstates in individuals with schizophrenia, as well as the association between changes in temporal parameters and psychiatric symptoms before and after treatment. This study seeks to evaluate the overall brain function and temporal dynamics in schizophrenia, as well as the impact of rTUS intervention on the temporal parameters of different microstates.	baseline and 4 weeks
Change of TEPs	TMS-evoked potentials (TEPs) from two target regions (the left DLPFC and the right STG) were measured in participants at baseline, after a single TUS intervention, and at 4 weeks. The study aimed to clarify the effects of rTUS treatment on the components of TEPs in individuals with schizophrenia, as well as the association between changes in TEP components and psychiatric symptoms.	baseline, Day1, and 4weeks

Collaborators and Investigators

• Sponsor: Shanghai Mental Health Center

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2023
• Primary Completion (Estimated): July 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: July 17, 2023
• First Submitted That Met QC Criteria: August 9, 2023
• First Posted (Actual): August 14, 2023

Study Record Updates

• Last Update Posted (Actual): March 26, 2025
• Last Update Submitted That Met QC Criteria: March 25, 2025
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Schizophrenia; Negative Symptoms; Transcranial Ultrasound Stimulation
• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Schizophrenia
• Other Study ID Numbers: 2022JC009

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No