N-Acetyl-Cysteine (NAC) in Early Phase Schizophrenia Spectrum Psychosis

Phase 2

Completed

Conditions: Schizophrenic Psychoses

Interventions: Drug: Placebo
Drug: n-acetylcysteine

Registration Number: NCT01354132

Lead Sponsor: Beth Israel Deaconess Medical Center

Brief Summary: The investigators seek to examine the effect of add-on N-Acetyl-Cysteine (NAC) in the early phase of schizophrenia spectrum illness in collaboration with researchers Kim Do, PhD, and Philippe Conus, MD in Switzerland. Modifications of brain structure are thought to occur during the pre-illness phase and around the transition to psychosis. Therefore, studying new treatments that could target changes occurring during this period is of critical importance.

Aims:

Does add-on NAC treatment in early psychosis influence:

* positive and negative symptoms

* extrapyramidal side-effects of other medication

* plasma concentration of glutathione

* Mismatch Negativity, a physiological marker

Detailed Description: The study proposes that a glutathione deficit leading to an abnormal response to oxidative stress is a vulnerability factor, combined with other brain specific factors, in brain functioning of some individuals with schizophrenia (Do et al., 2010). N-acetyl-cysteine is hypothesized to cross the blood-brain barrier and increase glutathione in the brain.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 20

Inclusion Criteria

Capacity to provide informed consent
DSM IV TR diagnosis of schizophrenia, schizophreniform, schizoaffective
Psychiatric and medical stability
Prescribing clinician's premission to participate, assurance of medical stability
Having met threshold criteria for psychosis on CAARMS (Comprehensive Assessment of at Risk Mental States Scale) Psychosis subscale
Up to 12 months of antipsychotic treatment

Exclusion Criteria

Severe medical comorbidities
Previous cerebral trauma
Substance induced psychosis or organic psychosis
Mental retardation
NAC allergy
Pregnancy, females and males planning pregnancy
Treatment with antioxidants
Insufficient command of English

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	matching effervescent tablets in water 2 in am and 1 in pm
n-acetyl-cysteine	n-acetylcysteine	N-Acetyl cysteine effervescent tablets in water 2 in am and 1 in pm for 28 weeks

Primary Outcome Measures

Name	Time	Method
Change in Negative Symptoms of Schizophrenia as Measured on the PANSS	at 6 months	Positive and Negative Symptom Scale was used to assess psychopathology. The sum of items N1 - N7 including N1) blunted affect, N2) emotional withdrawal, N3) poor rapport, N4) passive apathetic social withdrawal, N5) difficulty in abstract thinking, N6) lack of spontaneity and flow of conversation, and N7) sterotyped thinking were used to analyze negative symptoms of schizophrenia and were assessed for the previous week: RATING SCALE 1: Absent 2: Minimal 3: Mild 4: Moderate 5: Moderate Severe 6: Severe 7: Extreme The higher the score the worse the symptoms. The lowest possible score is 7 and the highest possible score is 49 .

Secondary Outcome Measures

Name	Time	Method
Global Assessment of Functioning (GAF)	at 6 months	Measure Description: Clinical Measure of Global level of Symptoms (Sx) and Functioning from 1 (Worst) to 100 (Best) in groups of 10: 100 - 91: Superior functioning 90 - 81: Absent or minimal Sx 80 - 71: If symptoms are present and expected 70 - 61:Some mild Sx 60 - 51: Moderate Sx 50 - 41: Serious Sx 40 - 31: Some impairment in reality testing or communication 30 - 21: Behavior is considerably influenced by delusions or hallucinations 20 - 11: Some danger of hurting self or others 10 - 1: Persistent danger of severely hurting self or others
Change in Cognition and Working Memory (MATRICS) Reasoning and Problem Solving	at 6 months	The MATRICS is neurocognitive battery designed to assess cognition. Problem Solving is a composite score based on the NAB Mazes. The score is a standardized T-Score which indicates the number of standard deviations above or below the mean, a T-Score of 50, in 10 point increments. A T-Score of 60 indicates 1 standard deviation above the mean and a T-Score of 40 indicates 1 standard deviation below the mean. A score below 50 indicated cognitive processing below that of an age and gender matched healthy control population. A score above 50 indicates cognitive processing above that of an age and gender matched healthy control population.
Social and Occupational Functioning Assessment Scale (SOFAS)	at 6 months	Measure of social and occupational functioning using the Social and Occupational Functioning Assessment Scale Measure Description: Rating of Overall Social and Occupational Functioning on a scale of 1 (worst) to 100 (best) in groups of 10: 100-91: Superior functioning 90-81: Good functioning 80-71: Slight impairment 70-61: Some difficulty 60-51: Moderate difficulty 50-41: Serious impairment 40-31: Major impairment 30-21: Inability to function in almost all areas 20-11: Unable to function independently 10-1: Unable to function without harming self or others
Change in Cognition and Working Memory (MATRICS) Verbal Learning	at 6 months	The MATRICS is neurocognitive battery designed to assess cognition. Verbal Learning is a composite score based on the Hopkins Verbal Learning Test-Revised: Immediate Recall. The score is a standardized T-Score which indicates the number of standard deviations above or below the mean, a T-Score of 50, in 10 point increments. A T-Score of 60 indicates 1 standard deviation above the mean and a T-Score of 40 indicates 1 standard deviation below the mean. A score below 50 indicated cognitive processing below that of an age and gender matched healthy control population. A score above 50 indicates cognitive processing above that of an age and gender matched healthy control population.
Change in Cognition and Working Memory (MATRICS) Visual Learning	at 6 months	The MATRICS is neurocognitive battery designed to assess cognition. Visual Learning is a composite score based on the Brief Visuospatial Memory test - Revised: Immediate Recall. The score is a standardized T-Score which indicates the number of standard deviations above or below the mean, a T-Score of 50, in 10 point increments. A T-Score of 60 indicates 1 standard deviation above the mean and a T-Score of 40 indicates 1 standard deviation below the mean. A score below 50 indicated cognitive processing below that of an age and gender matched healthy control population. A score above 50 indicates cognitive processing above that of an age and gender matched healthy control population.
Change in Cognition and Working Memory (MATRICS) Working Memory	at 6 months	The MATRICS is neurocognitive battery designed to assess cognition. Working Memory score is a composite score based on the following sub-test WMS-III Spatial Span and Letter-Number Span. The score is a standardized T-Score which indicates the number of standard deviations above or below the mean, a T-Score of 50, in 10 point increments. A T-Score of 60 indicates 1 standard deviation above the mean and a T-Score of 40 indicates 1 standard deviation below the mean. A score below 50 indicated cognitive processing below that of an age and gender matched healthy control population. A score above 50 indicates cognitive processing above that of an age and gender matched healthy control population.
GPxbc Glutathione Peroxidase Activity in Blood Cells	at 6 months	GPxBC is a measurement of glutathiione peroxidase enzymatic activity in glutathione synthesis and the redox system in blood cells. Measured as umol/min/gHb from blood cells.
Glutamine Brain Level for NAC Group	at 6 months	Glutamine is measured in the medial prefrontal cortex using Magnetic Resonance Spectroscopy (H-MRS) and is a chemical that works to protect the brain from high levels of excitatory chemicals such as glutamate.
Change in Positive Symptoms (PANSS)	at 6 months	Positive and Negative Symptom Scale was used to assess psychopathology. The Positive symptom subscale of schizophrenia includes the sum of items P1 -P7 including P1) Delusions, P2) conceptual Disorganization, P3) Hallunicatory Behavior, P4) Excitement, P5) Grandiosity, P6) Suspiciousness and Persecution, and P7) Hostility and were assessed for the previous week: RATING SCALE 1: Absent 2: Minimal 3: Mild 4: Moderate 5: Moderate Severe 6: Severe 7: Extreme The higher the score the worse the symptoms. The lowest possible score is 7 and the highest possible score is 49 .
Change in Cognition and Working Memory (MATRICS) Attention and Vigilance	at 6 months	The MATRICS is neurocognitive battery designed to assess cognition. Sustained attention and Vigilance is a composite score based on the Continuous Performance Test -Identical Pairs. The score is a standardized T-Score which indicates the number of standard deviations above or below the mean, a T-Score of 50, in 10 point increments. A T-Score of 60 indicates 1 standard deviation above the mean and a T-Score of 40 indicates 1 standard deviation below the mean. A score below 50 indicated cognitive processing below that of an age and gender matched healthy control population. A score above 50 indicates cognitive processing above that of an age and gender matched healthy control population.
Change in Blood Level of Glutathione	at 6 months	Glutathione is a tripeptide comprised of three amino acids (cysteine, glutamic acid, and glycine) and acts as an antioxidant, a free radical scavanger and a detoxifying agent. Glutathione is an important co-factor for the enzyme glutathione peroxidase used in the uptake of amino acids. The level of glutathione is measured in blood cells.
Glutathione Brain Level for NAC Group	at 6 months	measured by H-MRS in the medial prefrontal cortex Brain markers, glutathione was measured using Magnetic Resonance Spectroscopy (H-MRS) in the medial prefrontal cortex. Glutathione is a tripeptide comprised of three amino acids (cysteine, glutamic acid, and glycine) and acts as an antioxidant, a free radical scavanger and a detoxifying agent. Glutathione is an important co-factor for the enzyme glutathione peroxidase used in the uptake of amino acids.
Change in Cognition and Working Memory (MATRICS) Speed of Processing	at 6 months	The MATRICS is neurocognitive battery designed to assess cognition. Processing speed is a composite score including the following tests: Trail Making Test, BACS: Symbol Coding, Category Fluency: Animal Naming. The score is a standardized T-Score which indicates the number of standard deviations above or below the mean, a T-Score of 50, in 10 point increments. A T-Score of 60 indicates 1 standard deviation above the mean and a T-Score of 40 indicates 1 standard deviation below the mean. A score below 50 indicated cognitive processing below that of an age and gender matched healthy control population. A score above 50 indicates cognitive processing above that of an age and gender matched healthy control population.
Glutamine Brain Level for Placebo Group	at 6 months	Glutamine is measured in the medial prefrontal cortex using Magnetic Resonance Spectroscopy (H-MRS) and is a chemical that works to protect the brain from high levels of excitatory chemicals such as glutamate.
Glutamate Brain Level for NAC Group	at 6 months	Brain marker, glutamate, was measured using Magnetic Resonance Spectroscopy (H-MRS) in the medial prefrontal cortex. Glutamate is an excitatory neurotransmitter in the brain.
Glutamate Brain Level for Placebo Group	at 6 months	Glutamine is measured in the medial prefrontal cortex using Magnetic Resonance Spectroscopy (H-MRS) and is a chemical that works to protect the brain from high levels of excitatory chemicals such as glutamate.
Blood Plasma Level of Cysteine	at 6 months	Cysteine is an amino acid, a building block for proteins and is used throughout the body and was measured in blood plasma.
Glutathione Brain Level for Placebo Group	at 6 months	measured by H-MRS in the medial prefrontal cortex Brain markers, glutathione was measured using Magnetic Resonance Spectroscopy (H-MRS) in the medial prefrontal cortex. Glutathione is a tripeptide comprised of three amino acids (cysteine, glutamic acid, and glycine) and acts as an antioxidant, a free radical scavanger and a detoxifying agent. Glutathione is an important co-factor for the enzyme glutathione peroxidase used in the uptake of amino acids.
Myo-Inositol Brain Level for the NAC Group	at 6 months	Myo-Inositol is measured in the medial prefrontal cortex using Magnetic Resonance Spectroscopy (H-MRS)MRS and is a chemical that works to protect the brain from high levels of excitatory chemicals such as glutamate.
Myo-Inositol Brain Level for Placebo Group	at 6 months	Myo-Inositol is measured in the medial prefrontal cortex using Magnetic Resonance Spectroscopy (H-MRS)MRS and is a chemical that works to protect the brain from high levels of excitatory chemicals such as glutamate.

Trial Locations

Locations (2): Beth Israel Deaconess Medical Center
🇺🇸
Boston, Massachusetts, United States
Massachusetts Mental Health Center
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Boston, Massachusetts, United States