SchizophreniaPhase 1NCT01506765

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

A Phase 1 study testing N-Acetyl-Cysteine (NAC) in people with Schizophrenia, run by Centre Hospitalier Universitaire Vaudois.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for: Schizophrenia
What is being tested?: N-Acetyl-Cysteine (NAC)
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 13 participants
Where: No sites listed yet
Study dates: Aug 2003to Sep 2006
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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A change in primary antipsychotics from one medication to another will require participants to withdrawn from the study.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.

Who cannot join

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

About this study

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

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.

Read the 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.

Conditions: Schizophrenia
Being tested: N-Acetyl-Cysteine (NAC)
Keywords: Schizophrenia, glutathione, NAC, Neurological scales, Magnetic Resonance Spectroscopy (MRS), EEG/evoked potentials, fibroblasts, patients who receive NAC, patients who receive placebo
Medical subject headings: Schizophrenia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

Study groups in NCT01506765
Study group	Role	What they receive
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. Receives: 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 Receives: Drug: N-Acetyl-Cysteine (NAC)

What is being measured

The primary outcome is the main question the study is designed to answer.

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)
Measured: 8 months

Secondary outcomes (10)

frankfurt Complaint Questionnaire (FCQ)
Assessment of subjective troubles, " basic symptoms ": troubles of perceptive, cognitive or motor functions frequently observed in prodromal or remission phases.
Measured: 8 months
Global Assessment of Functioning - (GAF)
Assessment of the psychological, social and professional state of the patient at a given moment.
Measured: 8 months
Clinical Global Impression - (CGI)
Allows punctual evaluation of the severity of the disease, of the improvement and of the side effects
Measured: 8 months
Neuropsychological evaluation
The neuropsychological tests aim to assess cognitive functions : working memory, attention, planning; also include a WAIS
Measured: 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.
Measured: 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).
Measured: 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
Measured: 8 months
Blood and fibroblasts biochemistry
1. 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
Measured: 8 months
Neurological scales for the assessment of extrapyramidal symptoms
Simpson-Angus scale for extrapyramidal signs: tremor, rigidity, akinesia.
Measured: 8 months
Neurological scales for the assessment of extrapyramidal symptoms
Barnes scale: specific assessment of akathisia.
Measured: 8 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Aug 2003Sep 2006

First posted10 Jan 2012 (estimated)
Study startAug 2003
Primary completionDec 2004
Study completionSep 2006

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (5)Papers the sponsor has linked to this study.
Other trials for SchizophreniaStudies of the same condition, open and under way.
More trials run by Centre Hospitalier Universitaire VaudoisThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 13 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01506765
Sponsor's protocol ID: 106/03 CE
Status last verified: Jan 2012
First submitted: 3 Jan 2012
Last updated: 18 Jan 2012
Results posted: No
Data monitoring committee: Yes

Publications

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.
PubMed 11029642
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.
PubMed 10704955
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.
PubMed 12815674
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.
PubMed 10440953
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.
PubMed 22383949

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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All Schizophrenia trials

Study at a glance

From the registry record, last updated by the sponsor on 18 Jan 2012. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT01506765
Acronym / sponsor ID: 106/03 CE
Conditions: Schizophrenia
Keywords: Schizophrenia, glutathione, NAC, Neurological scales, Magnetic Resonance Spectroscopy (MRS), EEG/evoked potentials, fibroblasts, patients who receive NAC
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 13 participants (actual)
Lead sponsor: Centre Hospitalier Universitaire VaudoisUniversity, hospital or other
Study start: Aug 2003
Primary completion: Dec 2004 (actual)
Study completion: Sep 2006 (actual)
First posted: 10 Jan 2012 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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 design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 2

Arm	Type	Receives
patients who receive NAC first	Active comparator	Drug: N-Acetyl-Cysteine (NAC)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.
patients who receive placebo first	Placebo comparator	Drug: N-Acetyl-Cysteine (NAC)this patients will receive first placebo for a duration of 8 weeks, and after this 8 weeks their receive NAC for 8 weeks

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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.

Key exclusion criteria (8 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
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	Drug	patients who receive NAC first, patients who receive placebo first

Primary outcome

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)

10 secondary outcomes

frankfurt Complaint Questionnaire (FCQ)
Time frame: 8 months
Global Assessment of Functioning - (GAF)
Time frame: 8 months
Clinical Global Impression - (CGI)
Time frame: 8 months
Neuropsychological evaluation
Time frame: 8 months
Neurological scales for the assessment of extrapyramidal symptoms
Time frame: 8 months
• Magnetic Resonance Spectroscopy (MRS)
Time frame: 8 months
EEG/evoked potentials
Time frame: 8 months
Blood and fibroblasts biochemistry
Time frame: 8 months
Neurological scales for the assessment of extrapyramidal symptoms
Time frame: 8 months
Neurological scales for the assessment of extrapyramidal symptoms
Time frame: 8 months

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Jan 2012.
Background: PubMed 11029642Do 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.
Background: PubMed 10704955Mathalon 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.
Background: PubMed 12815674Terpstra 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.
Background: PubMed 10440953Trabesinger 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.
Derived from this study: PubMed 22383949Carmeli 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.

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Schizophrenia, Autism-Related Irritability
Not yet recruiting
Deep Brain Stimulation for Treatment-Resistant Schizophrenia
Treatment Resistant Disorders
Not yet recruitingObservational study
Sleep Monitoring for Early Detection of Relapse in People With Schizophrenia or Bipolar Disorder Receiving Usual Treatment
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Not yet recruitingPhase 1
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Healthy Adult Participants
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Kim Do, Professor study director

CNP/ LUNEP

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing N-Acetyl-Cysteine (NAC) in people with Schizophrenia, run by Centre Hospitalier Universitaire Vaudois.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Jan 2012. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Positive and Negative Syndrome Scale (PANSS) (time frame: 8 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01506765, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jan 2012.