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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called NaBen® (Sodium Benzoate) to determine its effectiveness in improving symptoms in adults with schizophrenia. NaBen® is taken as a pill and works alongside other treatments to potentially offer better symptom control. The study compares NaBen® to a placebo (a pill with no active medicine) to assess its safety and effectiveness. Adults diagnosed with schizophrenia for at least two years and with stable symptoms might be suitable for this trial. As a Phase 2/3 trial, this research measures the treatment's effectiveness in an initial, smaller group and represents the final step before FDA approval, offering participants a chance to contribute to potential advancements in schizophrenia treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that NaBen® appears promising as an additional treatment for schizophrenia. One study found that sodium benzoate, the main ingredient in NaBen®, reduced positive symptoms of schizophrenia, such as hallucinations or delusions, without increasing side effects.

Another study examined NaBen®'s safety in teenagers with schizophrenia, aiming to determine its safety and effectiveness for younger individuals.

Overall, research suggests that NaBen® is generally well-tolerated, with no major safety concerns reported. However, individual experiences may vary, so consulting a doctor will provide the best guidance. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for schizophrenia?

NaBen® is unique because it introduces a new approach to treating schizophrenia by potentially targeting glutamate regulation in the brain. Unlike traditional antipsychotics that primarily focus on dopamine pathways, NaBen® could offer a novel mechanism of action, which is particularly exciting for cases where current treatments fall short. Researchers are eager to see if this could lead to better symptom control and fewer side effects, offering new hope for those affected by this challenging condition.

What evidence suggests that NaBen® might be an effective treatment for schizophrenia?

Research has shown that NaBen®, which participants in this trial may receive, can significantly aid individuals with schizophrenia. One study demonstrated that adding NaBen® to regular treatment improved symptoms and enhanced cognitive function in those with long-term schizophrenia. Another study found that NaBen® might also assist in the early stages of psychosis, though results were mixed. NaBen® affects several brain pathways related to schizophrenia and is considered a promising option for enhancing current treatment plans. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39144112/

Add-on Sodium Benzoate and N-Acetylcysteine in Patients ... Sodium Benzoate (NaB) could have an additive with NAC to act on several pathophysiological mechanisms implicated in schizophrenia. Study design: ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT01908192

Adaptive Phase II Study to Evaluate the Safety & Efficacy of ... The purpose of this study is to determine if NaBen® is a safe and effective add-on treatment for schizophrenia in adolescents. Detailed Description. This is a ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7656289/

Effect of Sodium Benzoate vs Placebo Among Individuals With ... In this randomized clinical trial of 100 participants with early psychosis, there was no significant improvement in the total Positive and ...

4. jamanetwork.com jamanetwork.com/journals/jamapsychiatry/fullarticle/1746121

Add-on Treatment of Benzoate for Schizophrenia Conclusions and Relevance Benzoate adjunctive therapy significantly improved a variety of symptom domains and neurocognition in patients with chronic ...

5. psychiatrist.com psychiatrist.com/news/the-next-generation-of-schizophrenia-treatment-is-here/

The Next Generation of Schizophrenia Treatment is Here Luvadaxistat showed cognitive biomarker improvements in schizophrenia patients at a 50 mg dose, suggesting a non-linear dose response. Ω-NaBe ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34890931/

Efficacy and safety of add-on sodium benzoate, a D-amino ... Conclusion: Sodium benzoate can improve the positive symptoms of schizophrenia without any beneficial effect on other symptomatology, cognition, quality of life ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0149291822002909

Pharmacokinetics and Safety of Sodium Benzoate, a d- ... Highlights · Sodium benzoate is a lead compound of the novel mechanism, inhibition of D-amino acid oxidase, which is a new generation therapy for schizophrenia.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5383965/

The efficacy of sodium benzoate as an adjunctive treatment ... was based on 52 patients with chronic schizophrenia [12]. They reported a Cohen's effect size (d) of 1.53. Our patients (with early psychosis) ...