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

Not Applicable

Recruiting

• Conditions: Negative Symptoms of Schizophrenia

• Registration Number: NCT05985993
• Lead Sponsor: Shanghai Mental Health Center

Brief Summary

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.

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 Timeline

• Study First Submitted: 2023-07-17
• Study First Submitted QC: 2023-08-09
• Study First Posted: 2023-08-14
• Study Start: 2023-12-01
• Status Verified: 2024-11
• Last Update Submitted: 2025-03-25
• Last Update Posted: 2025-03-26
• Primary Completion: 2025-07-31
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 81

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Change from baseline in the Brief Negative Symptom Scale (BNSS)	baseline, 4 weeks and 8 weeks	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.
Change from baseline in the Scale for Assessment of Negative Symptoms(SANS)	baseline, 4 weeks and 8 weeks	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.
Change from baseline in Positive and Negative Syndrome Scale(PANSS)	baseline, 4 weeks and 8 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Change of cognitive Function	baseline, 4 weeks and 8 weeks	Change from baseline in MATRICS MCCB
Change of Multi-modal Brain Neuroimaging in structure	baseline and 4 weeks	Brain structure data will be acquired.
Change of Multi-modal Brain Neuroimaging in resting- state fMRI	baseline and 4 weeks	Resting-state fMRI data will be acquired.
Change of Multi-modal Brain Neuroimaging in 1H-MRS	baseline and 4 weeks	1H-MRS data will be acquired.
Change of EEG microstates	baseline and 4 weeks	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.
Change of TEPs	baseline, Day1, and 4weeks	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.

Trial Locations

Locations (1)

Shanghai Mental Health Center; 🇨🇳 Shanghai, Shanghai, China