Cadence discovery: study protocol for a dose-finding and mechanism of action clinical trial of sodium benzoate in people with treatment-refractory schizophrenia

Trials

Emma Whittle¹  Peter Donovan²  Gail Robinson³  George Bruxner⁴  Vikas Moudgil⁵  Ravinder Sohal⁵  Anne Gordon⁶  Digant Roy⁶  Gunter Hartel⁷  Luca Cocchi⁷  Lachlan Clarke⁸  Andrea Baker⁹  James G. Scott^1,10  Jacobus P. J. Ungerer^1,11 

[1] Clinical Pharmacology, Royal Brisbane and Women’s Hospital, 4006, Herston, QLD, Australia;Faculty of Medicine, The University of Queensland, Herston, QLD, Australia;Clinical Pharmacology, Royal Brisbane and Women’s Hospital, 4006, Herston, QLD, Australia;Faculty of Medicine, The University of Queensland, Herston, QLD, Australia;Metro North Mental Health Service, Caboolture Hospital, Caboolture, QLD, Australia;Metro North Mental Health Service, Caboolture Hospital, Caboolture, QLD, Australia;Metro North Mental Health Service, Royal Brisbane and Women’s Hospital, Herston, QLD, Australia;Metro North Mental Health Service, The Prince Charles Hospital, Chermside, QLD, Australia;QIMR Berghofer Medical Research Institute, Herston, QLD, Australia;QIMR Berghofer Medical Research Institute, Herston, QLD, Australia;Faculty of Medicine, The University of Queensland, Herston, QLD, Australia;QIMR Berghofer Medical Research Institute, Herston, QLD, Australia;Queensland Centre for Mental Health Research, The Park Centre for Mental Health, Wacol, QLD, Australia;QIMR Berghofer Medical Research Institute, Herston, QLD, Australia;Queensland Centre for Mental Health Research, The Park Centre for Mental Health, Wacol, QLD, Australia;Faculty of Medicine, The University of Queensland, Herston, QLD, Australia;Metro North Mental Health Service, Royal Brisbane and Women’s Hospital, Herston, QLD, Australia;School of Biomedical Sciences, The University of Queensland, Herston, QLD, Australia;Pathology Queensland, Royal Brisbane and Women’s Hospital, Herston, QLD, Australia;

关键词: Schizophrenia;    Adjunctive;    Treatment refractory;    Sodium benzoate;    Intervention;    RCT;    Clinical trial;    PANSS;   

DOI  :  10.1186/s13063-021-05890-6

来源: Springer

【 摘 要 】

BackgroundSchizophrenia is a persistent psychotic disorder often accompanied by severe disability and premature mortality. New pharmacological treatments are urgently needed. Sodium benzoate, a common food preservative holds potential to be an effective, accessible treatment for schizophrenia, though the optimal dosing and mechanism of action of the compound requires further investigation.MethodsIndividuals with persistent treatment-refractory schizophrenia (n=52) will be recruited. Patients will be randomised in a 1:1:1:1 ratio to receive treatment of one of three active doses (1000, 2000 or 4000 mg daily) of sodium benzoate or placebo for 6 weeks duration. The primary outcome measurement is change in the Positive and Negative Syndrome Scale (PANSS) total score. Secondary outcome measurements are PANSS subscales, Global Assessment of Function (GAF), Clinical Global Impression (CGI) and Patient Global Impression (PGI-I). Change in concentrations of peripheral amino acids (D-alanine, L-alanine, D-serine, L-serine, glycine and glutamate), plasma sodium benzoate, plasma catalase, 3-nitrotyrosine, malondialdehyde and high-sensitivity C-reactive protein (hs-CRP) will be determined as tertiary measures.DiscussionThis trial seeks to build upon previous research indicating potential efficacy of sodium benzoate for reduction of symptoms in individuals with treatment-refractory schizophrenia. The trial aims to improve the understanding of the mechanism of action of the compound.Trial registrationAustralian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12621000327886. Registered on 23 March 2021.

【 授权许可】

CC BY