Plain English Summary
Not provided at time of registration
Trial website
http://www.chuv.ch/psychiatrie/dpc_home/dpc_infos_organisation/dpc_cnp/dpc_cnp_schizo.html
Contact information
Type
Scientific
Primary contact
Dr Philippe Conus
ORCID ID
Contact details
Département de Psychiatrie
Route de Cery
Prilly
1008
Switzerland
philippe.conus@chuv.ch
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
13/08
Study information
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
Acronym
Study hypothesis
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
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)
Study design
Randomised multicentre parallel double-blind placebo-controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Can be found at http://www.chuv.ch/psychiatrie/dpc_home/dpc_infos_organisation/dpc_cnp/dpc_cnp_schizo.html
Condition
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 names
N-acetyl-cysteine (NAC)
Primary outcome measures
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
Secondary outcome measures
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)
Overall trial start date
15/12/2008
Overall trial end date
30/11/2011
Reason abandoned
Eligibility
Participant 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.
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
40
Participant 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
Recruitment start date
15/12/2008
Recruitment end date
30/11/2011
Locations
Countries of recruitment
Switzerland, United States of America
Trial participating centre
Département de Psychiatrie
Prilly
1008
Switzerland
Sponsor information
Organisation
Swiss National Science Foundation (Fonds National Suisse de la Recherche Scientifique [SNSF]) (Switzerland)
Sponsor details
SNSF 2009
Wildhainweg 3
PO Box 8232
Berne
CH-3001
Switzerland
+41 (0)31 308 22 22
kim.do@chuv.ch
Sponsor type
Research organisation
Website
Funders
Funder type
Charity
Funder name
Lausanne University Hospital, faculté de Biologie et de Médecine (CHUV) (Switzerland) - MTR Schizophrénie
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Society of the French-Swiss Lottery (Loterie Romande) (Switzerland)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Swiss National Science Foundation (SNSF) (Switzerland)
Alternative name(s)
Swiss National Science Foundation, Fonds National Suisse de la Recherche Scientifique, Fondo Nazionale Svizzero per la Ricerca Scientifica, Fonds National Suisse, Fondo Nazionale Svizzero, Schweizerischer Nationalfonds, SNF
Funding Body Type
private sector organisation
Funding Body Subtype
foundation
Location
Switzerland
Funder name
Stanley Thomas Johnson Foundation (Switzerland)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary
1. 2007 results in http://www.ncbi.nlm.nih.gov/pubmed/18004285
2. 2008 results in http://www.ncbi.nlm.nih.gov/pubmed/18436195
Publication citations
-
Results
Lavoie S, Murray MM, Deppen P, Knyazeva MG, Berk M, Boulat O, Bovet P, Bush AI, Conus P, Copolov D, Fornari E, Meuli R, Solida A, Vianin P, Cuénod M, Buclin T, Do KQ, Glutathione precursor, N-acetyl-cysteine, improves mismatch negativity in schizophrenia patients., Neuropsychopharmacology, 2008, 33, 9, 2187-2199, doi: 10.1038/sj.npp.1301624.
-
Results
Berk M, Copolov D, Dean O, Lu K, Jeavons S, Schapkaitz I, Anderson-Hunt M, Judd F, Katz F, Katz P, Ording-Jespersen S, Little J, Conus P, Cuenod M, Do KQ, Bush AI, N-acetyl cysteine as a glutathione precursor for schizophrenia--a double-blind, randomized, placebo-controlled trial., Biol. Psychiatry, 2008, 64, 5, 361-368, doi: 10.1016/j.biopsych.2008.03.004.