N-Acetyl Cysteine In Schizophrenia Resistant To Clozapine: A Double-Blind Randomised Placebo-Controlled Trial Targeting Negative Symptoms

• Register: ANZCTR
• Last refreshed on: 16 February 2021
• Main ID: ACTRN12615001273572
• Date of registration: 23/11/2015
• Prospective Registration: Yes
• Primary sponsor: The University of Melbourne
• Public title: N-Acetyl Cysteine In Schizophrenia Resistant To Clozapine: A Double-Blind Randomised Placebo-Controlled Trial Targeting Negative Symptoms
• Scientific title: N-Acetyl Cysteine In Schizophrenia Resistant To Clozapine: A Double-Blind Randomised Placebo-Controlled Trial Targeting Negative Symptoms
• Date of first enrolment: 23/03/2017
• Target sample size: 168
• Recruitment status: Stopped early
• URL: https://anzctr.org.au/ACTRN12615001273572.aspx
• Study type: Interventional
• Study design: Purpose: Treatment; Allocation: Randomised controlled trial; Masking: Blinded (masking used);Assignment: Parallel;Type of endpoint: Safety/efficacy;
• Phase: Phase 4

Countries of recruitment

Australia

Contacts

• Name: Prof David Castle

• Name: Prof David Castle

Key inclusion & exclusion criteria

Inclusion criteria: To be included the participants will be required to meet DSM5 criteria for SZ and:
- Have been on clozapine at an adequate dose, ascertained by a serum level of >350mcg/L for at least 6 months with residual symptom
- Have a PANSS score of 60 or at least two negative symptom items of >4
- Have the capacity to consent to the study
- Aged between 18 and 65 years
- Be utilising effective contraception if female and of childbearing age
Exclusion criteria: - Participants who are currently taking NAC
- Participants who are allergic to NAC or any component of the preparation
- Inability to comply with either the requirements of informed consent or the treatment protocol.
- People taking nitro-glycerine
- Diabetics on insulin replacement
- People taking Selenium or Vitamin E

Age minimum: 18 Years
Age maximum: 65 Years
Gender: Both males and females

Health Condition(s) or Problem(s) studied

Mental Health - Schizophrenia

Schizophrenia resistant to clozapine;
Schizophrenia resistant to clozapine

Intervention(s)

In this study, the efficacy and tolerability 2g daily of oral N-acetyl cysteine (NAC) will be compared to placebo as an augmenting strategy in patients with SZ who have proven ‘resistant’ to clozapine. All participants will remain on clozapine for the duration of the trial (i.e. 52 weeks). Adherence will be monitored with pill checks at each visit and the supervision of all doses.

Primary Outcome(s)

Negative symptoms as assessed with the Positive and Negative Symptoms Scale (PANSS)[8, 24 and 52 weeks.]

Secondary Outcome(s)

Quality of life as assessed by the Manchester Short Assessment of Quality of Life (MANSA) and the Assessment of Quality of Life (AQoL) [8, 24 and 52 weeks]

Biomarkers pertinent to glutathione (including thiols (such as GSH, cysteine, cysteinyl-glycine, N-acetylcysteine) and corresponding disulphides (such as glutathione disulphide (GSSG) and cysteine), other markers of oxidative stress (lipid peroxidation – thiobarbaturic acid -TBARS, DNA damage - 8-oxoguanine and protein carbonylation) and antioxidant levels).[8, 24 and 52 weeks]

Peripheral and cortical glutathione concentrations as assessed through blood samples and magnetic resonance spectroscopy, respectively.[8, 24 and 52 weeks]

Cognition as assessed by the MATRICS.[8,24 and 52 weeks]

Secondary ID(s)

Nil known

Source(s) of Monetary Support

NHMRC

Ethics review

Status: Approved
Approval date: 30/03/2016
Contact:

St Vincent's Hospital Melbourne Human Research Ethics Committee D

Results

• Results available: Yes
• Date Posted: 11/02/2021
• Date Completed: 10/02/2020