Clinical trial NCT06340789: Neurotransmitters in Treatment Resistant Schizophrenia Patients With add-on Sodium Benzoate
Official title: Functional Connectivity and Associated Neuropeptides Variations in Treatment Resistant Schizophrenia Patients: Treatment Efficacy of add-on Sodium Benzoate
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Symptom, Cognitive
Schizophrenia
Schizo Affective Disorder
Keywords: schizophrenia
sodium benzoate
cognition
treatment resistant schizophrenia
Lead sponsor: National Cheng-Kung University Hospital
Sponsor class: OTHER
First posted: 2024-04-02
Enrollment: 90
Sex: ALL
Minimum age (years): 20
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The design and instrument are identical for two years. This add-on sodium benzoate randomized, double-blinded, placebo-controlled trial which is a two-arm, 6-week follow-up trial. The 90 patients will be 2:1 (SB: placebo) randomly assigned to 1. Treatment with sodium benzoate (A); or 2. placebo (P). The group of sodium benzoate treatment will be divided into two subgroups: 1. Responder (AR), and nonresponder (AN), as illustrated in Figure 4. The response criteria is defined the improvement of 20% total PANSS score after 6-week SB treatment. The participants with TRS will be enrolled in this trail from 3 hospitals(National Cheng Kung University Hospital, Tainan Hospital, Ministry of Health and Welfare, Chia-Yi branch, Taichung Veteran General Hospital).
Primary purpose: TREATMENT

Brief summary: Although antipsychotic is effective for schizophrenia, however, still certain proportion of patients were not responsive to treatment. Treatment resistant schizophrenia (TRS) is accompanied by function decline and heavy burden. In recent decades, the biological mechanism of schizophrenia extended from dopamine theory to the role of glutamate system. This shift could be an alternative pathway to developing the treatment of TRS. Sodium benzoate (SB) could be an option as a glutamatergic agent for the patients with TRS. However, most evidence of SB is for treating patients with schizophrenia and other mental disorders but the evidence for treating patients with TRS is scarce. To predict the treatment response of SB will be an urgent topic in the future. Little is known about the precise medicine for treating patients with TRS. The present project will extend our pilot randomized clinical trial on SB for TRS. A total of 90 patients with TRS will be enrolled from three centers and will be assigned to 8 weeks of treatment with SB or placebo (2:1). A comprehensive battery of potential markers will be employed, including 1H- magnetic resonance spectroscopy (MRS), brain functional connectivity, genotyping, immune biomarkers, cognitive function, and clinical characteristics. The efficacy of SB on TRS will be confirmed in this project. Predictors for treatment response will be identified. Artificial intelligence algorithms will be used for probing the feasibility of precision medicine.

Detailed description: The design and instrument are identical for two years. This add-on sodium benzoate randomized, double-blinded, placebo-controlled trial which is a two-arm, 6-week follow-up trial. The 90 patients will be 2:1 (SB: placebo) randomly assigned to 1. Treatment with sodium benzoate (A); or 2. placebo (P). The group of sodium benzoate treatment will be divided into two subgroups: 1. Responder (AR), and nonresponder (AN), as illustrated in Figure 4. The response criteria is defined the improvement of 20% total PANSS score after 6-week SB treatment. The participants with TRS will be enrolled in this trail from 3 hospitals(National Cheng Kung University Hospital, Tainan Hospital, Ministry of Health and Welfare, Chia-Yi branch, Taichung Veteran General Hospital).

Eligibility criteria: Inclusion Criteria:

1. Fulfil the DSM5 criteria for schizophrenia or schizoaffective disorder
2. Research criteria for treatment resistance: little or no symptomatic response to multiple (at least two) antipsychotic treatment of an adequate duration (at least 6 weeks) and adequate doses (equivalent to at least 600 milliequivalent (meq)/day of chlorpromazine)
3. 6 month period without remission (i.e. ≥4 item-score for the positive symptoms on PANSS scale , especially delusional thoughts, conceptual disorganisation, excitements, grandiosity, hallucinatory behaviour, excitement, persecution, and hostility)
4. The persistence of illness was defined as a score of ≥4 (moderately ill) on the severity of illness subscale of the Clinical Global Impression scale (CGI-S), and a lack of stable period of good social occupational function.

Exclusion Criteria:

1. Current or previous diagnosis of concurrent DSM-5 disorder due to active medical problems, known neurological disease, or a contraindication to MRI scanning
2. Current diagnosis of substance-related disorder
3. Any acute or chronic medical condition
4. History of head trauma or neurological diseases.

Primary outcomes:
measure: Brain imaging, functional MRI
timeFrame: 1hours
Secondary outcomes:
measure: Clinical psychiatric condition, Positive and Negative Symptoms Scale (PANSS)
timeFrame: 20 minutes
measure: Wechsler adult intelligence scales 4th edition (WAIS-IV)
timeFrame: 1 hours
measure: Continuous performance test third edition (CPT-3)
timeFrame: 20 minutes
measure: Wisconsin card sorting test (WCST)
timeFrame: 20 minutes
Other outcomes:
Locations:
Study officials:
affiliation: Psychiatry department, National Cheng Kung University Hospital, Tainan, Taiwan
name: Yen-Kuang Yang, Dr
role: STUDY_DIRECTOR
References: