Condition category
Mental and Behavioural Disorders
Date applied
08/09/2009
Date assigned
14/10/2009
Last edited
14/10/2009
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

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

http://www.snf.ch/E/Pages/default.aspx

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

  1. 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.

  2. 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.

Additional files

Editorial Notes