NCT02026947

Sodium Benzoate for Treatment of Attenuated/Transient Psychosis. A Randomized Placebo-controlled Trial.

• Status: Withdrawn
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Niuvanniemi Hospital · Academic / Other
• Sex: All
• Age: 15 Years – 30 Years
• Healthy volunteers: Not accepted

Summary

The aim of this study is to investigate whether sodium benzoate is superior to placebo in decreasing symptoms among patients with attenuated/transient psychosis. A total of 140 patients will be randomized in 1:1 ratio to receive sodium benzoate 1 g/day or placebo for 12 weeks. Concerning statistical power, the number of patients is sufficient to obtain statistical significance for a clinically meaningful effect size of 0.40 (Cohen's d). The primary outcome measure is change in PANSS sum score of delusions, hallucinations, suspiciousness and conceptual disorganization (the PANSS items that are inclusion criteria) at week 12. Change in CGI score at week 12 is the other primary outcome measure. The secondary outcome measures are change in PANSS total score at week 12, CGI score at week 24, and GAF at weeks 12 and 24.

Detailed description

Early treatment of psychotic disorders results in better outcome, and several small randomized controlled trials (RCTs) have indicated that pharmacological treatment of prodromal patients with subthreshold psychosis might prevent transition to psychotic disorders. Use of risperidone had statistically significant effect at 6 months, but not at 12 months, and olanzapine has shown only a beneficial trend. The use of antipsychotics for the prevention of psychosis is controversial due their adverse effects and, therefore, use of better-tolerated agents such as natural compounds like benzoid acid or omega fatty acids might be a promising approach. Glutamatergic hypothesis has gained increasing support explaining symptoms of schizophrenia, and hypofunction of N-methyl-D-aspartate (NMDA) receptor is considered nowadays a major factor in the pathophysiology of the disease. Several NMDA-enhancing agents such as glycine, D-alanine, D-serine, sarcosine and bitopertin have shown beneficial effect as add-on treatments to antipsychotics. D-amino acid oxidase (DAAO) metabolizes D-alanine and D-serine, which are co-agonists of NMDA-receptor, and, therefore, decreasing DAAO activity results into enhancement of NMDA-receptor function. Recently, a randomized controlled trial in 52 patients with chronic schizophrenia was well tolerated and showed a robust beneficial effect of DAAO inhibitor sodium benzoate (1 g/d) as compared with placebo (effect size 1.76 for PANSS total scores; Tsai et al. 2012). The aim of this study is to investigate whether sodium benzoate is superior to placebo in decreasing symptoms among patients with attenuated/transient psychosis. A total of 140 patients will be randomized in 1:1 ratio to receive sodium benzoate 1 g/day or placebo for 12 weeks. Concerning statistical power, the number of patients is sufficient to obtain statistical significance for a clinically meaningful effect size of 0.40 (Cohen's d). The primary outcome measure is change in PANSS sum score of delusions, hallucinations, suspiciousness and conceptual disorganization (the PANSS items that are inclusion criteria) at week 12. Change in CGI score at week 12 is the other primary outcome measure. The secondary outcome measures are change in PANSS total score at week 12, CGI score at week 24, and GAF at weeks 12 and 24. An interim analysis will be done after obtaining results from the first 40 patients. If the effect size (Cohen's d) for primary outcome measures is less than 0.30, the study will be stopped prematurely.

Conditions

• Attenuated or Transient Psychosis

Interventions

Type	Name	Description
DRUG	Sodium Benzoate	0.5 g/day during the first week, 1.0 g/day for the next 11 weeks. One capsule at the morning for the first week. One capsule at the morning and one at the evening for 2-12 weeks.
DRUG	Placebo

Timeline

• Start date: 2014-02-01
• Primary completion: 2016-12-01
• Completion: 2016-12-01
• First posted: 2014-01-03
• Last updated: 2014-04-10

Locations

2 sites across 1 country: Finland