PMID- 34903265
OWN - NLM
STAT- MEDLINE
DCOM- 20211216
LR  - 20211217
IS  - 1745-6215 (Electronic)
IS  - 1745-6215 (Linking)
VI  - 22
IP  - 1
DP  - 2021 Dec 13
TI  - Cadence discovery: study protocol for a dose-finding and mechanism of action 
      clinical trial of sodium benzoate in people with treatment-refractory 
      schizophrenia.
PG  - 918
LID - 10.1186/s13063-021-05890-6 [doi]
LID - 918
AB  - BACKGROUND: Schizophrenia 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. 
      METHODS: Individuals 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. DISCUSSION: This 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 REGISTRATION: Australian New Zealand Clinical Trials Registry 
      (ANZCTR) ACTRN12621000327886 . Registered on 23 March 2021.
CI  - (c) 2021. The Author(s).
FAU - Baker, Andrea
AU  - Baker A
AD  - QIMR Berghofer Medical Research Institute, Herston, QLD, Australia.
AD  - Queensland Centre for Mental Health Research, The Park Centre for Mental Health, 
      Wacol, QLD, Australia.
FAU - Clarke, Lachlan
AU  - Clarke L
AD  - QIMR Berghofer Medical Research Institute, Herston, QLD, Australia.
AD  - Faculty of Medicine, The University of Queensland, Herston, QLD, Australia.
FAU - Donovan, Peter
AU  - Donovan P
AD  - Faculty of Medicine, The University of Queensland, Herston, QLD, Australia.
AD  - Clinical Pharmacology, Royal Brisbane and Women's Hospital, Herston, QLD, 4006, 
      Australia.
FAU - P J Ungerer, Jacobus
AU  - P J Ungerer J
AD  - School of Biomedical Sciences, The University of Queensland, Herston, QLD, 
      Australia.
AD  - Pathology Queensland, Royal Brisbane and Women's Hospital, Herston, QLD, 
      Australia.
FAU - Hartel, Gunter
AU  - Hartel G
AD  - QIMR Berghofer Medical Research Institute, Herston, QLD, Australia.
FAU - Bruxner, George
AU  - Bruxner G
AD  - Metro North Mental Health Service, Caboolture Hospital, Caboolture, QLD, 
      Australia.
FAU - Cocchi, Luca
AU  - Cocchi L
AD  - QIMR Berghofer Medical Research Institute, Herston, QLD, Australia.
FAU - Gordon, Anne
AU  - Gordon A
AD  - Metro North Mental Health Service, The Prince Charles Hospital, Chermside, QLD, 
      Australia.
FAU - Moudgil, Vikas
AU  - Moudgil V
AD  - Metro North Mental Health Service, Royal Brisbane and Women's Hospital, Herston, 
      QLD, Australia.
FAU - Robinson, Gail
AU  - Robinson G
AD  - Faculty of Medicine, The University of Queensland, Herston, QLD, Australia.
AD  - Metro North Mental Health Service, Caboolture Hospital, Caboolture, QLD, 
      Australia.
FAU - Roy, Digant
AU  - Roy D
AD  - Metro North Mental Health Service, The Prince Charles Hospital, Chermside, QLD, 
      Australia.
FAU - Sohal, Ravinder
AU  - Sohal R
AD  - Metro North Mental Health Service, Royal Brisbane and Women's Hospital, Herston, 
      QLD, Australia.
FAU - Whittle, Emma
AU  - Whittle E
AD  - Clinical Pharmacology, Royal Brisbane and Women's Hospital, Herston, QLD, 4006, 
      Australia.
FAU - Scott, James G
AU  - Scott JG
AUID- ORCID: 0000-0002-0744-0688
AD  - QIMR Berghofer Medical Research Institute, Herston, QLD, Australia. 
      james.scott@qimrberghofer.edu.au.
AD  - Queensland Centre for Mental Health Research, The Park Centre for Mental Health, 
      Wacol, QLD, Australia. james.scott@qimrberghofer.edu.au.
AD  - Faculty of Medicine, The University of Queensland, Herston, QLD, Australia. 
      james.scott@qimrberghofer.edu.au.
AD  - Metro North Mental Health Service, Royal Brisbane and Women's Hospital, Herston, 
      QLD, Australia. james.scott@qimrberghofer.edu.au.
LA  - eng
PT  - Journal Article
DEP - 20211213
PL  - England
TA  - Trials
JT  - Trials
JID - 101263253
RN  - 0 (Antipsychotic Agents)
RN  - OJ245FE5EU (Sodium Benzoate)
SB  - IM
MH  - *Antipsychotic Agents/adverse effects
MH  - Australia
MH  - Double-Blind Method
MH  - Humans
MH  - *Schizophrenia/diagnosis/drug therapy
MH  - Schizophrenia, Treatment-Resistant
MH  - Sodium Benzoate/adverse effects
MH  - Treatment Outcome
PMC - PMC8670031
OTO - NOTNLM
OT  - Adjunctive
OT  - Clinical trial
OT  - Intervention
OT  - PANSS
OT  - RCT
OT  - Schizophrenia
OT  - Sodium benzoate
OT  - Treatment refractory
COIS- The authors declare that they have no competing interests
EDAT- 2021/12/15 06:00
MHDA- 2021/12/17 06:00
PMCR- 2021/12/13
CRDT- 2021/12/14 06:06
PHST- 2021/04/08 00:00 [received]
PHST- 2021/11/28 00:00 [accepted]
PHST- 2021/12/14 06:06 [entrez]
PHST- 2021/12/15 06:00 [pubmed]
PHST- 2021/12/17 06:00 [medline]
PHST- 2021/12/13 00:00 [pmc-release]
AID - 10.1186/s13063-021-05890-6 [pii]
AID - 5890 [pii]
AID - 10.1186/s13063-021-05890-6 [doi]
PST - epublish
SO  - Trials. 2021 Dec 13;22(1):918. doi: 10.1186/s13063-021-05890-6.