NaBen® for Schizophrenia

Overseen By Yashar Salek, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: SyneuRx International (Taiwan) Corp

Must be taking: Antipsychotics

Must not be taking: Clozapine, Lithium, Antidepressants, others

Disqualifiers: Bipolar, Major depression, Substance abuse, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 8

280 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests NaBen®, a medication added to existing treatments, to see if it can improve symptoms in adults with schizophrenia who may not fully respond to their current treatments.

Will I have to stop taking my current medications?

The trial requires that your antipsychotic medication regimen remains unchanged during the study. If you are on other medications like lithium, antidepressants, or mood stabilizers, you should not have started or changed the dose within 16 weeks before the trial. For benzodiazepines or sleep medications, no changes should have been made within 4 weeks before the trial.

What data supports the effectiveness of the drug NaBen® (Sodium Benzoate) for treating schizophrenia?

Research on sodium benzoate, a component of NaBen®, suggests it may help enhance NMDA receptors in the brain, which are involved in schizophrenia. However, studies have shown mixed results, and more research is needed to confirm its effectiveness. ^{1 2 3 4 5}

Is sodium benzoate safe for use in humans?

Sodium benzoate has been studied as an add-on treatment for schizophrenia and has shown no obvious side effects at doses up to 2 grams per day for 6 weeks, indicating it is generally safe for human use. ^{1 3 6 7 8}

How is the drug NaBen® different from other schizophrenia treatments?

NaBen® (sodium benzoate) is unique because it acts as an NMDA receptor enhancer, which may help improve symptoms like cognitive impairment and negative symptoms in schizophrenia. Unlike traditional antipsychotics, it is used as an add-on treatment and is derived from a common food preservative, offering a novel approach to managing the condition. ^{1 3 6 8 9}

Eligibility Criteria

Adults aged 18-45 with schizophrenia, stable on current antipsychotic meds for at least 8 weeks, and in good physical health can join. They must not have been hospitalized for worsening symptoms within the last 3 months or have a history of substance abuse. Women must use contraception if not infertile.

Inclusion Criteria

I have not been hospitalized for my schizophrenia worsening in the last 3 months.

Subject has a negative routine urine illicit drug screening test (including heroin, amphetamines (including MDMA/ecstasy), cocaine, cannabis or PCP)

I am using reliable birth control or am infertile according to the study's definition.

Exclusion Criteria

My condition did not improve after trying two different antipsychotics.

I am currently taking or have taken clozapine.

You have a history of epilepsy, significant head injury, or any other neurological condition (except Tourette's syndrome) that could affect your thinking or mental health, as determined by the doctor.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Run-in

Eligible participants receive NaBen® or Placebo for 4 weeks to assess initial response

4 weeks

2 visits (in-person)

Double-Blind Treatment

Participants continue with NaBen® or Placebo for 8 weeks, with re-randomization for non-responders

8 weeks

4 visits (in-person)

Open-Label Extension

All participants receive NaBen® for an additional 52 weeks

52 weeks

Regular visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

1 visit (in-person)

Treatment Details

Interventions

• NaBen®
• Placebo

Trial Overview The trial tests NaBen® as an add-on treatment to improve schizophrenia symptoms against a placebo. It's randomized and placebo-controlled, involving screening, run-in, double-blind treatment phases over several weeks, followed by a year-long open-label extension.

Participant Groups

Group I: NaBen® Experimental Treatment 1 Intervention

NaBen® is a oral tablet (500 mg), which will be taken twice daily at a total dose of 1000 mg/day during this study.

Group II: Placebo Placebo Group 1 Intervention

The control treatment is placebo.

Who Is Running the Clinical Trial?

SyneuRx International (Taiwan) Corp

Lead Sponsor

Trials

4

Recruited

720+

Findings from Research

Sodium benzoate, when added to treatment for schizophrenia, significantly improves positive symptoms but does not have a beneficial effect on negative symptoms, cognitive function, or overall quality of life, based on a meta-analysis of four studies.

Patients receiving sodium benzoate experienced a higher incidence of extrapyramidal symptoms compared to the control group, indicating potential safety concerns despite its efficacy in addressing positive symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of add-on sodium benzoate, a D-amino acid oxidase inhibitor, in treatment of schizophrenia: A systematic review and meta-analysis. Seetharam, JC., Maiti, R., Mishra, A., et al.[2022]

In a meta-regression analysis of 18 double-blind, randomized, placebo-controlled trials involving 998 patients with stable schizophrenia, drugs were found to be more effective than placebo in reducing negative symptoms, although the effect size was small (Cohen's d: 0.208).

The study revealed a significant placebo response (Cohen's d: 2.909), indicating that factors like the number of trial arms, study sites, and industry sponsorship can influence the placebo effect, suggesting a need for improved trial designs to accurately assess treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of Placebo Response in Pharmacological Clinical Trials of Negative Symptoms in Schizophrenia: A Meta-regression Analysis. Fraguas, D., Díaz-Caneja, CM., Pina-Camacho, L., et al.[2022]

The placebo effect in schizophrenia clinical trials is becoming a significant challenge, making it harder to detect the effectiveness of new treatments and increasing development costs.

Understanding the central nervous system mechanisms behind the placebo effect and improving study designs could help mitigate this issue and enhance the reliability of clinical trial results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebo-related effects in clinical trials in schizophrenia: what is driving this phenomenon and what can be done to minimize it? Alphs, L., Benedetti, F., Fleischhacker, WW., et al.[2021]

In a pooled analysis of two 6-week trials involving 422 patients with schizophrenia, early response to antipsychotic treatment (low-dose olanzapine or haloperidol) significantly distinguished active drug from placebo, with a greater mean reduction in psychiatric symptoms observed at 2 weeks.

The study suggests that shortening the duration of placebo-controlled trials from 6 weeks to 2-4 weeks is feasible for identifying efficacy in acutely ill patients, as early treatment response was predictive of overall treatment success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early onset of antipsychotic action in schizophrenia: evaluating the possibility of shorter acute efficacy trials. Kinon, BJ., Chen, L., Stauffer, VL., et al.[2021]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy and safety of add-on sodium benzoate, a D-amino acid oxidase inhibitor, in treatment of schizophrenia: A systematic review and meta-analysis. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Predictors of Placebo Response in Pharmacological Clinical Trials of Negative Symptoms in Schizophrenia: A Meta-regression Analysis. [2022]

3. England pubmed.ncbi.nlm.nih.gov

The efficacy of sodium benzoate as an adjunctive treatment in early psychosis - CADENCE-BZ: study protocol for a randomized controlled trial. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Placebo-related effects in clinical trials in schizophrenia: what is driving this phenomenon and what can be done to minimize it? [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Early onset of antipsychotic action in schizophrenia: evaluating the possibility of shorter acute efficacy trials. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Positive effects of systemic sodium benzoate and olanzapine treatment on activities of daily life, spatial learning and working memory in ketamine-induced rat model of schizophrenia. [2023]

7. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Novel Treatment for the Most Resistant Schizophrenia: Dual Activation of NMDA Receptor and Antioxidant. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Effect of Sodium Benzoate vs Placebo Among Individuals With Early Psychosis: A Randomized Clinical Trial. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Effects of sodium benzoate on pre-pulse inhibition deficits and hyperlocomotion in mice after administration of phencyclidine. [2017]