Negative Symptoms of SchizophreniaNCT05985993
Precise Intervention Technology and Application of Low Intensity TUS on Negative Symptoms of Schizophrenia
A study testing low-intensity transcranial ultrasound stimulation (TUS) in people with Negative Symptoms of Schizophrenia, run by Shanghai Mental Health Center at 1 site in China.
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. Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Negative Symptoms of Schizophrenia
- What is being tested?
- low-intensity transcranial ultrasound stimulation (TUS)
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 78 participants
- Where
- 1 siteChina
- Study dates
- 1 Apr 2025to 31 May 2026
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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;
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
China1 site
Shanghai Mental Health Center
Shanghai, Shanghai Municipality, 200030
About this study
Official title: 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.
Read the 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.
- Conditions
- Negative Symptoms of Schizophrenia
- Being tested
- low-intensity transcranial ultrasound stimulation (TUS)
- Keywords
- Schizophrenia, Negative Symptoms, Transcranial Ultrasound Stimulation
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
low-intensity transcranial ultrasound stimulation (TUS)Device
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).
| Study group | Role | What they receive |
|---|---|---|
| single-target group (left DLPFC) | Active comparator | 27 eligible patients will be treated with active TUS for 4 weeks on the left DLPFC Receives: Device: low-intensity transcranial ultrasound stimulation (TUS) |
| both-target group (both left DLPFC and right STG) | Active comparator | 27 eligible patients will be treated with active TUS for 4 weeks on the both left DLPFC and right STG Receives: Device: low-intensity transcranial ultrasound stimulation (TUS) |
| sham group | Sham comparator | 27 eligible patients will be treated with sham TUS for 4 weeks on the left DLPFC and right STG, respectively. Receives: Device: low-intensity transcranial ultrasound stimulation (TUS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: baseline, 4 weeks and 8 weeks
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.
Measured: 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.
Measured: baseline, 4 weeks and 8 weeks
Secondary outcomes (6)
Change of cognitive Function
Change from baseline in MATRICS MCCB
Measured: baseline, 4 weeks and 8 weeks
Change of Multi-modal Brain Neuroimaging in structure
Brain structure data will be acquired.
Measured: baseline and 4 weeks
Change of Multi-modal Brain Neuroimaging in resting- state fMRI
Resting-state fMRI data will be acquired.
Measured: baseline and 4 weeks
Change of Multi-modal Brain Neuroimaging in 1H-MRS
1H-MRS data will be acquired.
Measured: baseline and 4 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.
Measured: 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.
Measured: baseline, Day1, and 4weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2023
- Study start1 Apr 2025
- Primary completion31 Mar 2026
- Study completion31 May 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Negative Symptoms of SchizophreniaStudies of the same condition, open and under way.
- More trials run by Shanghai Mental Health CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 78 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shanghai Mental Health Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05985993
- Sponsor's protocol ID
- 2022JC009
- Status last verified
- Jun 2026
- First submitted
- 17 Jul 2023
- Last updated
- 12 Jun 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Precise Intervention Technology and Application of Low Intensity Transcranial Ultrasound Stimulation (TUS) on Negative Symptoms of Schizophrenia
- ClinicalTrials.gov ID
- NCT05985993
- Acronym / sponsor ID
- 2022JC009
- Conditions
- Negative Symptoms of Schizophrenia
- Keywords
- Schizophrenia, Negative Symptoms, Transcranial Ultrasound Stimulation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 78 participants (actual)
- Lead sponsor
- Shanghai Mental Health CenterUniversity, hospital or other
- Study start
- 1 Apr 2025 (actual)
- Primary completion
- 31 Mar 2026 (actual)
- Study completion
- 31 May 2026 (actual)
- First posted
- 14 Aug 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| single-target group (left DLPFC) | Active comparator | Device: low-intensity transcranial ultrasound stimulation (TUS)27 eligible patients will be treated with active TUS for 4 weeks on the left DLPFC |
| both-target group (both left DLPFC and right STG) | Active comparator | Device: low-intensity transcranial ultrasound stimulation (TUS)27 eligible patients will be treated with active TUS for 4 weeks on the both left DLPFC and right STG |
| sham group | Sham comparator | Device: low-intensity transcranial ultrasound stimulation (TUS)27 eligible patients will be treated with sham TUS for 4 weeks on the left DLPFC and right STG, respectively. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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;
Key exclusion criteria (6 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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). | Device | both-target group (both left DLPFC and right STG), sham group, single-target group (left DLPFC) |
Primary outcome
Change from baseline in the Brief Negative Symptom Scale (BNSS)
Time frame: 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)
Time frame: 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)
Time frame: 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.
6 secondary outcomes
Change of cognitive Function
Time frame: baseline, 4 weeks and 8 weeks
Change of Multi-modal Brain Neuroimaging in structure
Time frame: baseline and 4 weeks
Change of Multi-modal Brain Neuroimaging in resting- state fMRI
Time frame: baseline and 4 weeks
Change of Multi-modal Brain Neuroimaging in 1H-MRS
Time frame: baseline and 4 weeks
Change of EEG microstates
Time frame: baseline and 4 weeks
Change of TEPs
Time frame: baseline, Day1, and 4weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jun 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing low-intensity transcranial ultrasound stimulation (TUS) in people with Negative Symptoms of Schizophrenia, run by Shanghai Mental Health Center at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline in the Brief Negative Symptom Scale (BNSS) (time frame: baseline, 4 weeks and 8 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jun 2026.