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

Negative Symptoms of Schizophrenia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05985993
• Other study ID #: 2022JC009
• Status: Not yet recruiting
• Phase: N/A
• Start date: September 1, 2023
• Est. completion date: December 31, 2025

Study information

• Verified date: August 2023
• Source: Shanghai Mental Health Center
• Contact: Dengtang LIU
• Phone: 021-34773434
• Email: erliu110[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 neural excitability and plasticity 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. A total of 102 schizophrenia inpatients 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, fNIRS ,and multi-modal MRI 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 102
• Est. completion date: December 31, 2025
• Est. primary completion date: July 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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.

Related Conditions & MeSH terms

• Negative Symptoms of Schizophrenia
• Schizophrenia

Intervention

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).

Locations

Country	Name	City	State
China	Shanghai Mental Health Center	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Mental Health Center

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Secondary	Cognitive Function	Change from baseline in MATRICS MCCB	baseline, 4 weeks and 8 weeks
Secondary	Change of Multi-modal Brain Neuroimaging in structure	Brain structure data will be acquired.	baseline and 4 weeks
Secondary	Change of Multi-modal Brain Neuroimaging in resting- state fMRI	Resting-state fMRI data will be acquired.	baseline and 4 weeks
Secondary	Change of Multi-modal Brain Neuroimaging in 1H-MRS	1H-MRS data will be acquired.	baseline and 4 weeks
Secondary	Change of functional near-infrared spectroscopy (fNIRS)	Functional near-infrared spectroscopy (fNIRS), a non-invasive neuroimaging technique that reflects changes in Oxy-Hb and Deoxy-Hb during brain activity, will be measured on left M1 region at baseline to evaluate the neuromodulation effect of TUS on neural activity.	baseline