Clinical trial NCT05985993: Precise Intervention Technology and Application of Low Intensity TUS on Negative Symptoms of Schizophrenia
Official title: Precise Intervention Technology and Application of Low Intensity Transcranial Ultrasound Stimulation (TUS) on Negative Symptoms of Schizophrenia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Negative Symptoms of Schizophrenia
Keywords: Schizophrenia
Negative Symptoms
Transcranial Ultrasound Stimulation
Lead sponsor: Shanghai Mental Health Center
Sponsor class: OTHER
First posted: 2023-08-14
Enrollment: 81
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change from baseline in the Brief Negative Symptom Scale (BNSS)
timeFrame: baseline, 4 weeks and 8 weeks
measure: Change from baseline in the Scale for Assessment of Negative Symptoms(SANS)
timeFrame: baseline, 4 weeks and 8 weeks
measure: Change from baseline in Positive and Negative Syndrome Scale(PANSS)
timeFrame: baseline, 4 weeks and 8 weeks
Secondary outcomes:
measure: Change of cognitive Function
timeFrame: baseline, 4 weeks and 8 weeks
measure: Change of Multi-modal Brain Neuroimaging in structure
timeFrame: baseline and 4 weeks
measure: Change of Multi-modal Brain Neuroimaging in resting- state fMRI
timeFrame: baseline and 4 weeks
measure: Change of Multi-modal Brain Neuroimaging in 1H-MRS
timeFrame: baseline and 4 weeks
measure: Change of EEG microstates
timeFrame: baseline and 4 weeks
measure: Change of TEPs
timeFrame: baseline, Day1, and 4weeks
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Mental Health Center
state: Shanghai
Study officials:
References: