Does oral N-acetyl-cysteine (NAC) improve schizophrenia symptoms?

ISRCTN	ISRCTN61794329
DOI	https://doi.org/10.1186/ISRCTN61794329
Protocol serial number	13/08
Sponsor	Swiss National Science Foundation (Fonds National Suisse de la Recherche Scientifique [SNSF]) (Switzerland)
Funders	Lausanne University Hospital, faculté de Biologie et de Médecine (CHUV) (Switzerland) - MTR Schizophrénie, Society of the French-Swiss Lottery (Loterie Romande) (Switzerland), Swiss National Science Foundation (SNSF) (Switzerland), Stanley Thomas Johnson Foundation (Switzerland)

Submission date: 08/09/2009
Registration date: 14/10/2009
Last edited: 14/10/2009

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Mental and Behavioural Disorders

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Philippe Conus
Scientific

Département de Psychiatrie
Route de Cery
Prilly
1008
Switzerland

Email	philippe.conus@chuv.ch

Study information

Primary study design	Interventional
Study design	Randomised multicentre parallel double-blind placebo-controlled trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	Effects of oral N-acetyl-cysteine (NAC) in the early phase of schizophrenia spectrum psychosis: a randomised parallel double-blind placebo-controlled trial
Study objectives	N-acetyl-cysteine (NAC), a common antitussive drug, is able to modulate the response to oxidative stress in body tissues. The aim of the study is to evaluate the impact of oral administration of NAC in the early phase of schizophrenia, on clinical, psychopathological, neuropsychological, biochemical and neuro-physiological variables. 1. Symptomatology: does the oral administration of NAC have an impact on evolution of positive and negative symptoms, cognitive deficits? 2. Side effects of neuroleptic treatment: does the oral administration of NAC have an impact on the side effects of antipsychotic treatment? 3. Glutathione (GSH) level: does the oral administration of NAC increase the plasma and brain concentration of GSH and related compounds? 4. Mismatch negativity (MMN): does the oral administration of NAC have an impact on MMN, a pre-attentive component of electro-encephalograms found to be impaired in schizophrenic patients?
Ethics approval(s)	The Faculty of Biology and Medicine - Ethics Commission of Clinical Research (Faculté de Biologie et de Médecine - Commission d'éthique de la recherche clinique) approved on the 10th July 2008 (ref: 13/08)
Health condition(s) or problem(s) studied	Early phase psychosis
Intervention	Each patient gets 2700 mg NAC or placebo per day during 24 weeks. Each patient gets the NAC pills/placebo each month for four weeks. After 24 weeks we stop the NAC/placebo and there is a follow-up after 4 weeks. Then we do the last clinical interviews and take urine and blood samples.
Intervention type	Drug
Phase	Phase II
Drug / device / biological / vaccine name(s)	N-acetyl-cysteine (NAC)
Primary outcome measure(s)	Improvement of the negative symptoms, measured with the Positive and Negative Syndrome Scale (PANSS - score: 1 = absence of the symptom to 7 = extreme symptoms), measured at baseline, then every month for 7 months
Key secondary outcome measure(s)	1. Clinical outcome: decreased risk of relapse during the outcome period measured with the PANSS, GAF and SOFAS) 2. Neuropsychological outcome: improvement of cognition (measured with the global score of the "MATRICS" battery); and improvement of the working memory (measured with the "MATRICS" battery) 3. Functional electroencephalographic outcome: improvement of the MMN (or prevention/delay); change of the P3, response to visual stimuli 4. Magnetic resonance by spectroscopy (MRS): higher cerebral level of glutathione measured by MRS. Changes in connectivity measured by MRS and DSI, diffusion spectrum imaging. Measured at baseline (V1) and after 6 months. 5. Stratification: better response to treatment in sub-groups (high-risk/low risk GCLC genotype and/or anomalies in GSH system)
Completion date	30/11/2011

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	All
Target sample size at registration	40
Key inclusion criteria	1. Capability to provide informed consent 2. Male or female aged 15 to 35 years with sufficient command of French language 3. Having met threshold criteria for psychosis as defined by the "Psychosis threshold" subscale of the Comprehensive Assessment of at Risk Mental States Scale (CAARMS). This threshold is based on a combination of intensity and duration of psychotic symptoms.
Key exclusion criteria	1. Severe somatic comorbidities: peptic ulcer disease, chronic inflammatory pathologies, infectious pathologies including human immunodeficiency virus (HIV), pathologies of the immune system, organic cerebral diseases, tumours, abnormal renal, hepatic, thyroid or haematological findings 2. Previous cerebral trauma 3. Substance induced psychosis or organic psychosis 4. Mental retardation (intellectual quotient [IQ] less than 70 and alteration or significant adaptation deficit). We will assess the IQ only in the case of necessity when we doubt about the intellectual skills of a patient. 5. NAC allergy 6. Treatment with antioxidants (vitamin E, selenium, multivitamins, etc.) 7. Insufficient command of French
Date of first enrolment	15/12/2008
Date of final enrolment	30/11/2011

Locations

Countries of recruitment

Switzerland
United States of America

Study participating centre

Département de Psychiatrie

Prilly
1008
Switzerland

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/08/2008		Yes	No
Results article	results	01/09/2008		Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Study website	Study website	11/11/2025	11/11/2025	No	Yes