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

Schizophrenia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01506765
• Other study ID #: 106/03 CE
• Status: Completed
• Phase: Phase 1
• First received: January 3, 2012
• Last updated: January 17, 2012
• Start date: August 2003
• Est. completion date: September 2006

Study information

• Verified date: January 2012
• Source: Centre Hospitalier Universitaire Vaudois
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationSwitzerland: Swissmedic
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: September 2006
• Est. primary completion date: December 2004
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Schizophrenia

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire Vaudois

References & Publications (4)

Do KQ, Trabesinger AH, Kirsten-Krüger M, Lauer CJ, Dydak U, Hell D, Holsboer F, Boesiger P, Cuénod M. Schizophrenia: glutathione deficit in cerebrospinal fluid and prefrontal cortex in vivo. Eur J Neurosci. 2000 Oct;12(10):3721-8. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	Global Assessment of Functioning - (GAF)	Assessment of the psychological, social and professional state of the patient at a given moment.	8 months	No
Secondary	Clinical Global Impression - (CGI)	Allows punctual evaluation of the severity of the disease, of the improvement and of the side effects	8 months	No
Secondary	Neuropsychological evaluation	The neuropsychological tests aim to assess cognitive functions : working memory, attention, planning; also include a WAIS	8 months	No
Secondary	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	No
Secondary	• 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	No
Secondary	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	No
Secondary	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	No
Secondary	Neurological scales for the assessment of extrapyramidal symptoms	Simpson-Angus scale for extrapyramidal signs: tremor, rigidity, akinesia.	8 months	No
Secondary	Neurological scales for the assessment of extrapyramidal symptoms	Barnes scale: specific assessment of akathisia.	8 months	No