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

NCT ID: NCT06340789

Last Updated: 2024-04-15

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-04-10
• Study Completion Date: 2025-04-30

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).

Conditions

Symptom, Cognitive; Schizophrenia; Schizo Affective Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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

with sodium benzoate 2g/day

Group Type: ACTIVE_COMPARATOR

Sodium Benzoate 2gram/day

Intervention Type: DRUG

the add-on sodium benzoate with conventional pharmacological treatment

Treatment resistant schizophrenia patients with augmentation of placebo

with placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

the add-on placebo with conventional pharmacological treatment

Interventions

Sodium Benzoate 2gram/day

the add-on sodium benzoate with conventional pharmacological treatment

Intervention Type: DRUG

Placebo

the add-on placebo with conventional pharmacological treatment

Intervention Type: DRUG

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.

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cheng-Kung University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Yen-Kuang Yang, Dr

Role: STUDY_DIRECTOR

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

Central Contacts

Yen-Kuang Yang, Dr

Role: CONTACT

ykyang@mail.ncku.edu.tw

+886-6-2353535 ext. 5202

Li- Chung Huang, Dr

Role: CONTACT

huanglichung@hotmail.com

0911889866

Other Identifiers

A-BR-110-49

Identifier Type: -

Identifier Source: org_study_id