None listed
Conditions
Brief summary
A proportion of individuals with schizophrenia (SZ) do not respond adequately to clozapine, with anything from 40-60% of individuals having residual symptoms at the completion of an adequate trial of clozapine. Agents that could work synergistically with clozapine to improve efficacy whilst not increasing the side effect burden are both desired and necessary to improve the lives of individuals with clozapine-resistant SZ, such as N-acetyl cysteine (NAC). Our group has extensive experience with NAC with pilot data support from a rigorous RCT exploring the efficacy of NAC in clozapine-resistant SZ. This project grant seeks funding to expand this work by conducting a multi-site randomised placebo-controlled trial of NAC in the treatment of clozapine-resistant schizophrenia, with 8, 24 and 52 week endpoints. We will target negative symptoms as our primary outcome measure, with quality of life and cognition as secondary outcomes. We will examine both peripheral and cortical glutathione concentrations. Additionally, we will measure a number of other biomarkers pertinent to the glutathione hypothesis. Such analyses will further our understanding the role of oxidative stress in SZ. The trial is a randomised controlled double-blinded superiority trial of two parallel patient groups. The study will be conducted across four Australian sites, namely Melbourne (St Vincent’s Mental Health Service), Sydney (Cumberland Hospital), Adelaide (Northern Adelaide Local Health Network), and Brisbane (Metro South Addiction and Mental Health Service). Forty-two patients will be recruited from each of the sites, with a total target of 168 patients aged 18 - 65 years meeting DSM-5 criteria for schizophrenia. Block randomisation will be used. This trial, if successful, will establish a cheap, safe and easy-to-use agent (NAC) as a ‘go to’ adjunct in patients only partly responsive to clozapine.
Interventions
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.
Sponsors
The University of Melbourne
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Healthy volunteers
No
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
Outcome results
None listed