Schizophrenia, Related Troubles and Glutathione: Clinical Trial. Effects of Oral Administration of N-Acetylcysteine (NAC) on the Brain Glutathione Level and on the Symptoms of Schizophrenia

NCT01506765 | Completed Phase 1 DMC

• 1 other identifier: 106/03 CE
• Study Type: interventional
• Target: 13
• Locations: 0 countries
• Sites: N/A

Brief Summary

The results of the study "schizophrenia, related disorders and glutathione" conducted at the Laboratory of Psychiatric Neuroscience (LUNEP) DUPA of Lausanne, reinforce the hypothesis proposed that a deficit intracerebral glutathione is a vulnerability factor for Schizophrenia at least for a subgroup of patients. While pursuing the baseline study, it is appropriate now to try to restore a higher level of glutathione in patients to see if this increase is accompanied by an improvement in symptoms, particularly negative symptoms and disorders cognitive, particularly resistant to current therapy. N-acetyl-cystein (NAC) is a precursor of glutathione which is used clinically for various indications, well tolerated even at high doses. The investigators propose a double-blind cross-over with the aim to study if the N-acetyl-cystein (at a dose of oral 2g/day) leads on the one hand a rising glutathione brain (measured in resonance magnetic spectroscopic) and also improved patients' conditions (determined by clinical assessments, psychopathological, neuropsychological, biochemical and physiological), while recording any side effects. As a first step, this study should include at least thirty patients and last for two to three years. It is important to note that this is not a study of medication suggested by a pharmaceutical industry, but a medical search.

Conditions

Schizophrenia

Keywords

Schizophrenia; glutathione; NAC; Neurological scales; Magnetic Resonance Spectroscopy (MRS); EEG/evoked potentials; fibroblasts; patients who receive NAC; patients who receive placebo

Outcome Measures

Primary Outcomes (1)

• Positive and Negative Syndrome Scale (PANSS)

  Improvment of the negative symptoms, measured with the PANSS: positive and negative syndrome scale". (Score:1= absence of the symptom - 7= extreme symptoms)

  8 months

Secondary Outcomes (10)

• frankfurt Complaint Questionnaire (FCQ)

  8 months

• Global Assessment of Functioning - (GAF)

  8 months

• Clinical Global Impression - (CGI)

  8 months

• Neuropsychological evaluation

  8 months

• Neurological scales for the assessment of extrapyramidal symptoms

  8 months

Study Arms (2)

patients who receive NAC first

ACTIVE COMPARATOR

this group will receive 2g/day of NAC (2 caps of 0.5g twice day)for a duration of 8 weeks first, and after this 8 weeks their receive placebo for 8 weeks.

Drug: N-Acetyl-Cysteine (NAC)

patients who receive placebo first

PLACEBO COMPARATOR

this patients will receive first placebo for a duration of 8 weeks, and after this 8 weeks their receive NAC for 8 weeks

Drug: N-Acetyl-Cysteine (NAC)

Interventions

N-Acetyl-Cysteine (NAC) DRUG

Once included, the patients will be randomly placed in two groups: one group (1) will receive 2 g/day of NAC (2caps of 0.5g twice a day) and the other group (2) a placebo, for a duration of 8 weeks. At the end of the 8 weeks, group (2) will receive NAC and (1) the placebo for another 8 weeks

patients who receive NAC first; patients who receive placebo first

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• patients (male or female, aged 18 to 65 years, QI\>70) meeting the DSM-IV criteria (established by a senior psychiatrist) for schizophrenia and have the capacity to consent to the study. The study population include both inpatients and outpatients who are currently taking at least one of the following:Olanzapine, Clozapine, Haloperidol, Risperidone, Flupenthixol, or Fluphenazine. The following guidelines have been established for potential medication changes that patients may undergo during the course of the trial.
• dose changes to existing medication (either increases or decreases in dose) will be accepted and participants will be allowed to continue with the trial.
• A change in primary antipsychotics from one medication to another will require participants to withdrawn from the study.
• An addiction of another antipsychotic, secondary to the existing antipsychotic treatment (primary antipsychotic) will be acceptable providing that there isn't a complete change from one antipsychotic to another.

You may not qualify if:

• pregnancy
• acute psychotic state, preventing the patient cooperation
• co-morbidity with drug dependency
• organic cerebral disease, major somatic diseases
• abnormal renal, hepatic, thyroid or hematological findings
• treatment with a regulator of mood(lithium, valproate, topiramate, lamotrigine et carbamazepine)
• allergy to NAC
• treatment with antioxidants

Sponsors & Collaborators

• Centre Hospitalier Universitaire Vaudois: lead

Related Publications (5)

• Do KQ, Trabesinger AH, Kirsten-Kruger M, Lauer CJ, Dydak U, Hell D, Holsboer F, Boesiger P, Cuenod M. Schizophrenia: glutathione deficit in cerebrospinal fluid and prefrontal cortex in vivo. Eur J Neurosci. 2000 Oct;12(10):3721-8. doi: 10.1046/j.1460-9568.2000.00229.x.

  PMID: 11029642 BACKGROUND

• Mathalon DH, Ford JM, Pfefferbaum A. Trait and state aspects of P300 amplitude reduction in schizophrenia: a retrospective longitudinal study. Biol Psychiatry. 2000 Mar 1;47(5):434-49. doi: 10.1016/s0006-3223(99)00277-2.

  PMID: 10704955 BACKGROUND

• Terpstra M, Henry PG, Gruetter R. Measurement of reduced glutathione (GSH) in human brain using LCModel analysis of difference-edited spectra. Magn Reson Med. 2003 Jul;50(1):19-23. doi: 10.1002/mrm.10499.

  PMID: 12815674 BACKGROUND

• Trabesinger AH, Weber OM, Duc CO, Boesiger P. Detection of glutathione in the human brain in vivo by means of double quantum coherence filtering. Magn Reson Med. 1999 Aug;42(2):283-9. doi: 10.1002/(sici)1522-2594(199908)42:23.0.co;2-q.

  PMID: 10440953 BACKGROUND

• Carmeli C, Knyazeva MG, Cuenod M, Do KQ. Glutathione precursor N-acetyl-cysteine modulates EEG synchronization in schizophrenia patients: a double-blind, randomized, placebo-controlled trial. PLoS One. 2012;7(2):e29341. doi: 10.1371/journal.pone.0029341. Epub 2012 Feb 22.

  PMID: 22383949 DERIVED

MeSH Terms

Conditions

Schizophrenia

Interventions

Acetylcysteine

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Kim Do, Professor

  CNP/ LUNEP

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 3, 2012
• First Posted: January 10, 2012
• Study Start: August 1, 2003
• Primary Completion: December 1, 2004
• Study Completion: September 1, 2006
• Last Updated: January 18, 2012

Record last verified: 2012-01