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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01354132
First Posted: May 16, 2011
Last Update Posted: July 5, 2017
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.
Collaborator:
Center de Neurosciences Psychiatrique, Lausanne, Switzerland
Information provided by (Responsible Party):
Larry Seidman, Beth Israel Deaconess Medical Center
May 13, 2011
May 16, 2011
March 17, 2017
June 7, 2017
July 5, 2017
May 2011
August 2014   (Final data collection date for primary outcome measure)
Change in Negative Symptoms of Schizophrenia as Measured on the PANSS [ Time Frame: 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 .

Improvement of negative symptoms on the PANSS [ Time Frame: within 6 months of NAC treatment ]
Positive and Negative Syndrome Scale
Complete list of historical versions of study NCT01354132 on ClinicalTrials.gov Archive Site
  • Change in Positive Symptoms (PANSS) [ Time Frame: 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 .

  • Global Assessment of Functioning (GAF) [ Time Frame: 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

  • Social and Occupational Functioning Assessment Scale (SOFAS) [ Time Frame: 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) Speed of Processing [ Time Frame: 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.
  • Change in Cognition and Working Memory (MATRICS) Working Memory [ Time Frame: 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.
  • Change in Cognition and Working Memory (MATRICS) Attention and Vigilance [ Time Frame: 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 Cognition and Working Memory (MATRICS) Verbal Learning [ Time Frame: 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 [ Time Frame: 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) Reasoning and Problem Solving [ Time Frame: 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.
  • Change in Blood Level of Glutathione [ Time Frame: 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.
  • Blood Plasma Level of Cysteine [ Time Frame: 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.
  • GPxbc Glutathione Peroxidase Activity in Blood Cells [ Time Frame: 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 [ Time Frame: 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.
  • Glutamine Brain Level for Placebo Group [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.
  • Glutathione Brain Level for NAC Group [ Time Frame: 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.
  • Glutathione Brain Level for Placebo Group [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.
  • Improved positive and general symptoms (PANSS) and functional level (GAF & SOFAS) [ Time Frame: within 6 months of NAC treatment ]
    Positive and Negative Syndrome Scale Global Assessment of Functioning Social and Occupational Functioning Assessment Scale
  • Improved cognition and working memory (MATRICS) [ Time Frame: at 24 weeks of NAC treatment ]
    The MATRICS is neurocognitive battery designed to assess cognition in psychopharmacology studies
  • Improved EEG/Evoked potentials (Mismatch Negativity) [ Time Frame: at 24 weeks of NAC treatment ]
    Mismatch Negativity, a component of auditory evoked potentials
  • Improved plasma glutathione [ Time Frame: within 24 weeks of NAC treatment ]
    Plasma levels of glutathione, plasma amino acids and genetic analysis of enzymes involved in glutathione metabolism
Not Provided
Not Provided
 
N-Acetyl-Cysteine (NAC) in Early Phase Schizophrenia Spectrum Psychosis
Effects of Oral N-Acetyl-Cysteine (NAC) in the Early Phase of Schizophrenia Spectrum Psychosis: Randomized, Parallel, Double- Blind, Placebo Controlled Trial

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
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.
Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Schizophrenic Psychoses
  • Drug: n-acetylcysteine
    900 mg effervescent PharmaNAC tablet in water or juice: two tablets in the AM, one tablet in PM
    Other Name: PharmaNAC
  • Drug: Placebo
    Placebo tablets are placed in water or juice in the AM and PM
  • Active Comparator: n-acetyl-cysteine
    N-Acetyl cysteine effervescent tablets in water 2 in am and 1 in pm for 28 weeks
    Intervention: Drug: n-acetylcysteine
  • Placebo Comparator: Placebo
    matching effervescent tablets in water 2 in am and 1 in pm
    Intervention: Drug: Placebo
Do KQ, Conus P, Cuenod M. Redox dysregulation and oxidative stress in schizophrenia: nutrigenetics as a challenge in psychiatric disease prevention. World Rev Nutr Diet. 2010;101:131-53. doi: 10.1159/000314518. Epub 2010 Apr 30. Review.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
20
August 2014
August 2014   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years to 35 Years   (Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT01354132
2008P000460
107865 ( Other Identifier: FDA IND )
Yes
Not Provided
Not Provided
Larry Seidman, Beth Israel Deaconess Medical Center
Beth Israel Deaconess Medical Center
Center de Neurosciences Psychiatrique, Lausanne, Switzerland
Study Director: Ann Cousins, PhD, APRN Beth Israel Deaconess Medical Center
Study Chair: T. U. Wilson Woo, MD, PhD Harvard Medical School
Beth Israel Deaconess Medical Center
June 2017

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