Neurotransmitters in Treatment Resistant Schizophrenia Patients With add-on Sodium Benzoate

NCT06340789 | Recruiting Phase 2 DMC

• 1 other identifier: A-BR-110-049
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

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.

Conditions

Symptom, Cognitive; Schizophrenia; Schizo Affective Disorder

Keywords

schizophrenia; sodium benzoate; cognition; treatment resistant schizophrenia

Outcome Measures

Primary Outcomes (1)

• Brain imaging, functional MRI

  All participants were scanned using a 1.5 Tesla GE scanner with eight channel head coils. 1H-MRS was performed to assess the concentrations of excitatory, glutamine, glutamate, glutamate complex (Glx), GABA and other neurometabolites. A three-dimensional T1-weighted inversion recovery magnetic resonance imaging (MRI) scan was performed in all participants, axial MRI three-dimensional brain volume, echo time (TE) = 2.9 ms, repetition time (TR) = 7.7, inversion time = 450 ms, flip angle = 12°, field of view =230 mm, matrix size = 256 × 256, and slice thickness = 1.0 mm

  1hours

Secondary Outcomes (4)

• Clinical psychiatric condition, Positive and Negative Symptoms Scale (PANSS)

  20 minutes

• Wechsler adult intelligence scales 4th edition (WAIS-IV)

  1 hours

• Continuous performance test third edition (CPT-3)

  20 minutes

• Wisconsin card sorting test (WCST)

  20 minutes

Study Arms (2)

Treatment resistant schizophrenia patients with augmentation of sodium benzoate 2g/day

ACTIVE COMPARATOR

with sodium benzoate 2g/day

Drug: Sodium Benzoate 2gram/day

Treatment resistant schizophrenia patients with augmentation of placebo

PLACEBO COMPARATOR

with placebo

Drug: Placebo

Interventions

Sodium Benzoate 2gram/day DRUG

the add-on sodium benzoate with conventional pharmacological treatment

Treatment resistant schizophrenia patients with augmentation of sodium benzoate 2g/day

Placebo DRUG

the add-on placebo with conventional pharmacological treatment

Treatment resistant schizophrenia patients with augmentation of placebo

Eligibility Criteria

• Age: 20 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Fulfil the DSM5 criteria for schizophrenia or schizoaffective disorder
• 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)
• 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)
• 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.

You may not qualify if:

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

Sponsors & Collaborators

• National Cheng-Kung University Hospital: lead

Study Sites (1)

Taichung Veterans General Hospital Chiayi Branch

Chiayi City, 600, Taiwan

RECRUITING

MeSH Terms

Conditions

Neurobehavioral Manifestations; Schizophrenia; Psychotic Disorders; Schizophrenia, Treatment-Resistant

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Study Officials

• Yen-Kuang Yang, Dr

  Psychiatry department, National Cheng Kung University Hospital, Tainan, Taiwan

  STUDY DIRECTOR

Central Study Contacts

Yen-Kuang Yang, Dr

CONTACT

+886-6-2353535; ykyang@mail.ncku.edu.tw

Li- Chung Huang, Dr

CONTACT

0911889866; huanglichung@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: November 3, 2021
• First Posted: April 2, 2024
• Study Start: November 18, 2021
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): April 30, 2028
• Last Updated: June 16, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)