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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| frankfurt Complaint Questionnaire (FCQ) | Assessment of subjective troubles, " basic symptoms ": troubles of perceptive, cognitive or motor functions frequently observed in prodromal or remission phases. | 8 months |
| Global Assessment of Functioning - (GAF) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Kim Do, Professor | CNP/ LUNEP | Study Director |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 11029642 | Background | 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. | |
| 10704955 | 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. |
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|
Assessment of the psychological, social and professional state of the patient at a given moment. |
| 8 months |
| Clinical Global Impression - (CGI) | Allows punctual evaluation of the severity of the disease, of the improvement and of the side effects | 8 months |
| Neuropsychological evaluation | The neuropsychological tests aim to assess cognitive functions : working memory, attention, planning; also include a WAIS | 8 months |
| Neurological scales for the assessment of extrapyramidal symptoms | AIMS (Abnormal Involuntary Movements Scale): quantitative assessment of secondary hyperkinesia (excluding tremor) due to neuroleptics. | 8 months |
| • Magnetic Resonance Spectroscopy (MRS) | 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). | 8 months |
| EEG/evoked potentials | 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 | 8 months |
| Blood and fibroblasts biochemistry | 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 | 8 months |
| Neurological scales for the assessment of extrapyramidal symptoms | Simpson-Angus scale for extrapyramidal signs: tremor, rigidity, akinesia. | 8 months |
| Neurological scales for the assessment of extrapyramidal symptoms | Barnes scale: specific assessment of akathisia. | 8 months |
| 12815674 | 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. |
| 10440953 | 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. |
| 22383949 | Derived | 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. |
| ID | Term |
|---|---|
| D012559 | Schizophrenia |
| ID | Term |
|---|---|
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D000111 | Acetylcysteine |
| ID | Term |
|---|---|
| D003545 | Cysteine |
| D000603 | Amino Acids, Sulfur |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
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