Clinical trial NCT06904092: Efficacy and Mechanisms of TUS on Cognitive Deficits in Schizophrenia: Based on the Hippocampal-Prefrontal Circuit
Official title: Efficacy and Mechanisms of Transcranial Ultrasound Stimulation (TUS) on Cognitive Deficits in Schizophrenia：based on the Hippocampal-Prefrontal Circuit
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Cognitive Deficit in Schizophrenia
Keywords: Schizophrenia; Cognitive Deficit; Transcranial Ultrasound Stimulation; Hippocampus- Prefrontal Circuit
Lead sponsor: Shanghai Mental Health Center
Sponsor class: OTHER
First posted: 2025-04-01
Enrollment: 105
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: Cognitive deficit is a core symptom of schizophrenia related to poorer functional outcome. Prior studies indicated that abnormalities in the hippocampus-prefrontal circuit and glutamate/GABA imbalances may lead to cognitive deficits. Based on the current background and our previous studies, it has been proved that TUS can modulate neural excitability and plasticity in the hippocampus. In this double-blind, randomized study, the efficacy of different treatment options and mechanisms of TUS on cognitive deficits will be investigated.

Detailed description: Cognitive deficit is a core symptom of schizophrenia related to poorer functional outcome which remains largely treatment refractory. Prior studies indicated that abnormalities in the hippocampus-prefrontal circuit and glutamate/GABA imbalances may be the root causes of cognitive deficits. Transcranial ultrasound stimulation (TUS), an emerging non-invasive neuromodulation technique with deep penetration ability, can modulate neural excitability and plasticity in the hippocampus. This is a 4-week double-blind randomized trial of TUS for cognitive deficits in schizophrenia, with either left hippocampus or left dorsolateral prefrontal cortex (DLPFC) or both targeted. This study aims to determine the efficacy of TUS and to reveal its underlying neural mechanism, especially with the hippocampus-prefrontal circuit, by means of TUS, as to assess cortical inhibition and excitability, EEG source imaging, and multi-model MRI. 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 ;
* Age18-50, right-handed, Han nationality;
* Presence of cognitive deficit: defined as d' value \<0.5 in associative memory test;
* 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, pregnancy 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 benzodiazepine drugs (diazepam \> 10mg/day, clonazepam \> 2mg/day etc.), if necessary, remain unchanged during the course of treatment;
* Contraindications to TUS and MRI are present.

Primary outcomes:
measure: Change from baseline in associative memory test score
timeFrame: baseline, 4 weeks and 8 weeks
Secondary outcomes:
measure: Change of information processing speed and attention/vigilance
timeFrame: baseline, 4 weeks and 8 weeks
measure: Change of working memory
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
measure: Change of CGI score
timeFrame: baseline, 4 weeks and 8 weeks
measure: Change from baseline in UCSD Performance-based Skills Assessment-Brief (UPSA-B)
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 TEPs
timeFrame: baseline and 4 weeks
measure: Change of 64 channels EEG
timeFrame: baseline and 4 weeks
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Mental Health Center
state: Shanghai
Study officials:
References: