Precise Intervention Technology and Application of Low Intensity TUS on Negative Symptoms of Schizophrenia
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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N/A |
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 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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: single-target group (left DLPFC) 34 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) 34 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 34 eligible patients will be treated with sham 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).
|
Outcome Measures
Primary Outcome Measures
- 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
- 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 functional near-infrared spectroscopy (fNIRS) [baseline]
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.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Meet the DSM-5 diagnostic criteria for schizophrenia or schizoaffective disorder;
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Age18-50, right-handed, Han nationality;
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Score of at least 1 item from N1 to N7 in PANSS is ≥4 (moderate or above);
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Be in a stable condition, received second-generation antipsychotics for at least 4 weeks or more;
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Written informed consent;
Exclusion Criteria:
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Current or past neurological illness, severe physical diseases, substance abuse or alcohol dependence, mental retardation, pregnant or lactation;
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Uncooperative or risky patients with high excitement, stupor, disorder of words and deeds, negative suicide, etc.;
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History of MECT or other physical therapy within 6 months;
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History of epilepsy, or epileptic waves on the baseline EEG;
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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;
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Contraindications to TUS and MRI are present.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Shanghai Mental Health Center | Shanghai | Shanghai | China | 200030 |
Sponsors and Collaborators
- Shanghai Mental Health Center
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2022JC009