Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01506765
Recruitment Status : Completed
First Posted : January 10, 2012
Last Update Posted : January 18, 2012
Sponsor:
Information provided by (Responsible Party):
Dresse Kim Q. Do, Centre Hospitalier Universitaire Vaudois

Tracking Information
First Submitted Date  ICMJE January 3, 2012
First Posted Date  ICMJE January 10, 2012
Last Update Posted Date January 18, 2012
Study Start Date  ICMJE August 2003
Actual Primary Completion Date December 2004   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 5, 2012)
Positive and Negative Syndrome Scale (PANSS) [ Time Frame: 8 months ]
Improvment of the negative symptoms, measured with the PANSS: positive and negative syndrome scale". (Score:1= absence of the symptom - 7= extreme symptoms)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 17, 2012)
  • frankfurt Complaint Questionnaire (FCQ) [ Time Frame: 8 months ]
    Assessment of subjective troubles, " basic symptoms ": troubles of perceptive, cognitive or motor functions frequently observed in prodromal or remission phases.
  • Global Assessment of Functioning - (GAF) [ Time Frame: 8 months ]
    Assessment of the psychological, social and professional state of the patient at a given moment.
  • Clinical Global Impression - (CGI) [ Time Frame: 8 months ]
    Allows punctual evaluation of the severity of the disease, of the improvement and of the side effects
  • Neuropsychological evaluation [ Time Frame: 8 months ]
    The neuropsychological tests aim to assess cognitive functions : working memory, attention, planning; also include a WAIS
  • Neurological scales for the assessment of extrapyramidal symptoms [ Time Frame: 8 months ]
    AIMS (Abnormal Involuntary Movements Scale): quantitative assessment of secondary hyperkinesia (excluding tremor) due to neuroleptics.
  • • Magnetic Resonance Spectroscopy (MRS) [ Time Frame: 8 months ]
    A MRS method has originally been developed for the determination of brain GSH levels in vivo (Trabesinger et al., 1999), allowing us to observe a 51% GSH decrease in prefrontal cortex of schizophrenic patients (Do et al., 2000).
  • EEG/evoked potentials [ Time Frame: 8 months ]
    Anomalies of amplitude and latency of the P300 wave evoked under the "auditory oddball" paradigm are reliable neurophysiological markers of schizophrenia, correlating with the negative symptoms
  • Blood and fibroblasts biochemistry [ Time Frame: 8 months ]
    I. Plasma GSH and metabolites, plasma amino acids, particularly the sulfur containing ones II. activity of enzymes involved in GSH metabolism III. genetic analysis of enzymes involved in GSH metabolism IV. cell counts and tests of hepatic, renal and thyroid functions
  • Neurological scales for the assessment of extrapyramidal symptoms [ Time Frame: 8 months ]
    Simpson-Angus scale for extrapyramidal signs: tremor, rigidity, akinesia.
  • Neurological scales for the assessment of extrapyramidal symptoms [ Time Frame: 8 months ]
    Barnes scale: specific assessment of akathisia.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 5, 2012)
  • Frankfurter Beschwerde Fragebogen (QPF) [ Time Frame: 8 months ]
    Assessment of subjective troubles, " basic symptoms ": troubles of perceptive, cognitive or motor functions frequently observed in prodromal or remission phases.
  • Global Assessment of Functioning - (GAF) [ Time Frame: 8 months ]
    Assessment of the psychological, social and professional state of the patient at a given moment.
  • Clinical Global Impression - (CGI) [ Time Frame: 8 months ]
    Allows punctual evaluation of the severity of the disease, of the improvement and of the side effects
  • Neuropsychological evaluation [ Time Frame: 8 months ]
    The neuropsychological tests aim to assess cognitive functions : working memory, attention, planning; also include a WAIS
  • Neurological scales for the assessment of extrapyramidal symptoms [ Time Frame: 8 months ]
    Simpson-Angus and Barnes Scales
    • AIMS (Abnormal Involuntary Movements Scale): quantitative assessment of secondary hyperkinesia (excluding tremor) due to neuroleptics.
    • Simpson-Angus scale for extrapyramidal signs: tremor, rigidity, akinesia.
    • Barnes scale: specific assessment of akathisia.
  • • Magnetic Resonance Spectroscopy (MRS) [ Time Frame: 8 months ]
    A MRS method has originally been developed for the determination of brain GSH levels in vivo (Trabesinger et al., 1999), allowing us to observe a 51% GSH decrease in prefrontal cortex of schizophrenic patients (Do et al., 2000).
  • EEG/evoked potentials [ Time Frame: 8 months ]
    Anomalies of amplitude and latency of the P300 wave evoked under the "auditory oddball" paradigm are reliable neurophysiological markers of schizophrenia, correlating with the negative symptoms
  • Blood and fibroblasts biochemistry [ Time Frame: 8 months ]
    I. Plasma GSH and metabolites, plasma amino acids, particularly the sulfur containing ones II. activity of enzymes involved in GSH metabolism III. genetic analysis of enzymes involved in GSH metabolism IV. cell counts and tests of hepatic, renal and thyroid functions
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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: Double-blind and Crossover Study
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.
Detailed Description 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-cysteine (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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Schizophrenia
Intervention  ICMJE Drug: N-Acetyl-Cysteine (NAC)
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
Study Arms  ICMJE
  • Active Comparator: patients who receive NAC first
    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.
    Intervention: Drug: N-Acetyl-Cysteine (NAC)
  • Placebo Comparator: patients who receive placebo first
    this patients will receive first placebo for a duration of 8 weeks, and after this 8 weeks their receive NAC for 8 weeks
    Intervention: Drug: N-Acetyl-Cysteine (NAC)
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 5, 2012)
13
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE September 2006
Actual Primary Completion Date December 2004   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01506765
Other Study ID Numbers  ICMJE 106/03 CE
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Dresse Kim Q. Do, Centre Hospitalier Universitaire Vaudois
Study Sponsor  ICMJE Centre Hospitalier Universitaire Vaudois
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Kim Do, Professor CNP/ LUNEP
PRS Account Centre Hospitalier Universitaire Vaudois
Verification Date January 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP