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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
Results First Submitted: March 17, 2017  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition: Schizophrenic Psychoses
Interventions: Drug: n-acetylcysteine
Drug: Placebo

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants were recruited at two sites, Lausanne University Hospital, Department of Psychiatry, Lausanne, Switzerland and at the Commonwealth Research Center of Beth Israel Deaconess Medical Center Boston, Massachusetts

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
320 signed consent 133 declined to participate 124 excluded - 65 by Physician decision, 59 subject withdrew 63 met all inclusion and no exclusion criteria 31 to NAC and 30 to placebo

Reporting Groups
  Description
N-acetyl-cysteine

N-Acetyl cysteine effervescent tablets in water 2 in am and 1 in pm for 28 weeks

n-acetylcysteine: 900 mg effervescent PharmaNAC tablet in water or juice: two tablets in the AM, one tablet in PM

Placebo

matching effervescent tablets in water 2 in am and 1 in pm

n-acetylcysteine: 900 mg effervescent PharmaNAC tablet in water or juice: two tablets in the AM, one tablet in PM


Participant Flow for 3 periods

Period 1:   Randomization
    N-acetyl-cysteine   Placebo
STARTED   32 [1]   31 [2] 
COMPLETED   31   30 
NOT COMPLETED   1   1 
Physician Decision                1                0 
Withdrawal by Subject                0                1 
[1] 1 never took study medication dropped by physician decision (White matter lesion on MRI)
[2] 1 never took study medication due to subject withdrawal

Period 2:   Double Blind (Visits 1-7)
    N-acetyl-cysteine   Placebo
STARTED   31 [1]   30 [2] 
Completed More Than 1 Visit   4   5 
Stopped After First Visit   3   2 
Didn't Complete at Least 1 Visit   2   4 
COMPLETED   22   19 
NOT COMPLETED   9   11 
Adverse Event                1                0 
Withdrawal by Subject                8                11 
[1] 9 did not compete 7 study visits
[2] 11 did not compete 7 study visits

Period 3:   1 Month Post Study Medication
    N-acetyl-cysteine   Placebo
STARTED   22   19 
1 Follow-up Visit (Visit 8)   21   16 
COMPLETED   21   16 
NOT COMPLETED   1   3 
Withdrawal by Subject                1                3 



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
N-acetyl-cysteine

N-Acetyl cysteine effervescent tablets in water 2 in am and 1 in pm for 28 weeks

n-acetylcysteine: 900 mg effervescent PharmaNAC tablet in water or juice: two tablets in the AM, one tablet in PM

Placebo

matching effervescent tablets in water 2 in am and 1 in pm

n-acetylcysteine: 900 mg effervescent PharmaNAC tablet in water or juice: two tablets in the AM, one tablet in PM

Total Total of all reporting groups

Baseline Measures
   N-acetyl-cysteine   Placebo   Total 
Overall Participants Analyzed 
[Units: Participants]
 31   30   61 
Age 
[Units: Years]
Mean (Standard Deviation)
     
Participants Analyzed 
[Units: Participants]
 31   30   61 
   26.1  (6.1)   24.7  (5.9)   25.4  (6.0) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
     
Participants Analyzed 
[Units: Participants]
 31   30   61 
Female      5  16.1%      9  30.0%      14  23.0% 
Male      26  83.9%      21  70.0%      47  77.0% 
Race/Ethnicity, Customized 
[Units: Participants]
Count of Participants
     
Black or African American       
Participants Analyzed 
[Units: Participants]
 31   30   61 
Black or African American   5   7   12 
White       
Participants Analyzed 
[Units: Participants]
 31   30   61 
White   25   22   47 
Maghreb       
Participants Analyzed 
[Units: Participants]
 31   30   61 
Maghreb   1   1   2 
Hispanic or Latino       
Participants Analyzed 
[Units: Participants]
 31   30   61 
Hispanic or Latino   0   1   1 
Not Hispanic or Latino       
Participants Analyzed 
[Units: Participants]
 31   30   61 
Not Hispanic or Latino   31   29   60 
Region of Enrollment 
[Units: Participants]
Count of Participants
     
United States       
Participants Analyzed 
[Units: Participants]
 31   30   61 
United States   6   4   10 
Switzerland       
Participants Analyzed 
[Units: Participants]
 31   30   61 
Switzerland   26   27   53 
Positive and Negative Symptom Scale (PANSS) [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
     
Positive PANSS Symptoms       
Participants Analyzed 
[Units: Participants]
 31   30   61 
Positive PANSS Symptoms   14.3  (5.4)   15.0  (5.6)   14.7  (16.4) 
Negative Symptoms       
Participants Analyzed 
[Units: Participants]
 31   30   61 
Negative Symptoms   15.6  (5.0)   17.3  (6.3)   16.4  (5.7) 
[1]

Clinical Measure of Positive (7 items P1-P7) Negative Symptoms (7 items N1-N7) General Psychopathology Symptoms (G1-G16) total of 30 items

Assessed in 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 30 and the highesr possible score is 210.

Global Assessment of Functioning (GAF) [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
     
Participants Analyzed 
[Units: Participants]
 31   30   61 
   54  (10.8)   51.6  (12.8)   52.8  (11.8) 
[1]

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

Duration of Psychosis [1] 
[Units: Days]
Mean (Standard Deviation)
     
Participants Analyzed 
[Units: Participants]
 31   30   61 
   848  (767)   747  (693)   796  (726) 
[1] Duration of time in days since onset of psychosis
Social and Occupational Functioning Assessment Scale (SOFAS) [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
     
Participants Analyzed 
[Units: Participants]
 31   30   61 
   55.8  (11.0)   53.5  (13.0)   54.7  (12.0) 
[1]

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

MATRICS Consensus Cognitive Battery (MCCB) excluding MISCEIT managing emotions test) [1] [2] 
[Units: Standardized T Scores]
Mean (Standard Deviation)
     
Processing Speed       
Participants Analyzed 
[Units: Participants]
 20   16   36 
Processing Speed   37.72  (11.22)   35.53  (16.31)   36.75  (13.48) 
Sustained Attention       
Participants Analyzed 
[Units: Participants]
 20   16   36 
Sustained Attention   40.23  (11.71)   32.67  (13.15)   36.87  (12.35) 
Working Memory       
Participants Analyzed 
[Units: Participants]
 20   16   36 
Working Memory   47.56  (9.70)   38.87  (15.09)   43.70  (12.10) 
Verbal Learning       
Participants Analyzed 
[Units: Participants]
 20   16   36 
Verbal Learning   40.94  (10.09)   40.93  (13.73)   40.94  (11.71) 
Visual Learning       
Participants Analyzed 
[Units: Participants]
 20   16   36 
Visual Learning   41.06  (10.01)   44.86  (14.42)   42.75  (11.97) 
Problem Solving       
Participants Analyzed 
[Units: Participants]
 20   16   36 
Problem Solving   48.00  (11.69)   39.93  (12.76)   44.41  (12.17) 
[1] The MCCB has 6 cognitive factors including: 1) processing speed (Trail Making Test, BACS: Symbol Coding, Category Fluency: Animal Naming), 2) sustained attention (Continuous Performance Test –Identical Pairs), 3) working memory (WMS-III Spatial Span and Letter-Number Span), 4) verbal learning (Hopkins Verbal Learning Test-Revised: Immediate Recall), 5) visual learning (Brief Visuospatial Memory test – Revised: Immediate Recall) and 6) problem solving (NAB Mazes). The T-score of 50 is an average score. Scores below 50 indicates cognitive processing lower than age matched healthy populations.
[2] Numbers in each group analyzed based on those who completed baseline and post testing.
Antipsychotic Medication Chlorpromazine Equivalents [1] 
[Units: Milligrams]
Mean (Standard Deviation)
     
Participants Analyzed 
[Units: Participants]
 31   30   61 
   309  (252)   309  (188)   309  (220) 
[1] Dose of current antipsychotic medication in chlorpromazine equivalents
Blood Marker - Cysteine [1] 
[Units: uM (micrometer)]
Mean (Standard Deviation)
     
Participants Analyzed 
[Units: Participants]
 31   30   61 
   261.3  (37.6)   254.0  (33.6)   257.7  (35.7) 
[1] Cysteine is an amino acid, a building block for proteins and is used throughout the body and was measured in blood plasma.
Blood Marker - GPxbc- Glutathione peroxidase [1] 
[Units: umol/min/gHb]
Mean (Standard Deviation)
     
Participants Analyzed 
[Units: Participants]
 31   30   61 
   21.24  (7.5)   21.01  (6.93)   21.13  (7.17) 
[1] 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.
Blood Marker - Glutathione [1] 
[Units: mM (millimolar) in blood cells]
Mean (Standard Deviation)
     
Participants Analyzed 
[Units: Participants]
 31   30   61 
   0.77  (0.21)   0.84  (0.27)   0.81  (0.24) 
[1] 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.
Brain Marker - Glutamine and myo-Inositol [1] [2] 
[Units: mM (millimolar)]
Mean (Standard Deviation)
     
Glutamine       
Participants Analyzed 
[Units: Participants]
 13   12   25 
Glutamine   3.25  (0.51)   2.93  (0.48)   3.10  (0.50) 
Myo-Inositol       
Participants Analyzed 
[Units: Participants]
 13   12   25 
Myo-Inositol   6.25  (1.05)   6.28  (0.62)   6.26  (0.84) 
[1] Brain levels of glutamine and myo-Inositol were measured using Magnetic ResonanceSpectroscopy (H-MRS), both are chemicals that work to protect the brain from high levels of excitatory chemicals such as glutamate.
[2] MRS was completed on fewer participants.
Brain Marker - Glutathione and Glutamate [1] [2] 
[Units: mM (millimolar)]
Mean (Standard Deviation)
     
Glutathione       
Participants Analyzed 
[Units: Participants]
 13   12   25 
Glutathione   0.87  (0.23)   1.12  (0.18)   0.99  (0.21) 
Glutamate       
Participants Analyzed 
[Units: Participants]
 13   12   25 
Glutamate   10.12  (0.80)   10.64  (1.23)   10.37  (1.01) 
[1] Brain markers, glutathione and glutamate were 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. Glutamate is an excitatory neurotransmitter in the brain.
[2] Only 25 participants had the MRS.


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Change in Negative Symptoms of Schizophrenia as Measured on the PANSS   [ Time Frame: at 6 months ]

2.  Secondary:   Change in Positive Symptoms (PANSS)   [ Time Frame: at 6 months ]

3.  Secondary:   Global Assessment of Functioning (GAF)   [ Time Frame: at 6 months ]

4.  Secondary:   Social and Occupational Functioning Assessment Scale (SOFAS)   [ Time Frame: at 6 months ]

5.  Secondary:   Change in Cognition and Working Memory (MATRICS) Speed of Processing   [ Time Frame: at 6 months ]

6.  Secondary:   Change in Cognition and Working Memory (MATRICS) Working Memory   [ Time Frame: at 6 months ]

7.  Secondary:   Change in Cognition and Working Memory (MATRICS) Attention and Vigilance   [ Time Frame: at 6 months ]

8.  Secondary:   Change in Cognition and Working Memory (MATRICS) Verbal Learning   [ Time Frame: at 6 months ]

9.  Secondary:   Change in Cognition and Working Memory (MATRICS) Visual Learning   [ Time Frame: at 6 months ]

10.  Secondary:   Change in Cognition and Working Memory (MATRICS) Reasoning and Problem Solving   [ Time Frame: at 6 months ]

11.  Secondary:   Change in Blood Level of Glutathione   [ Time Frame: at 6 months ]

12.  Secondary:   Blood Plasma Level of Cysteine   [ Time Frame: at 6 months ]

13.  Secondary:   GPxbc Glutathione Peroxidase Activity in Blood Cells   [ Time Frame: at 6 months ]

14.  Secondary:   Glutamine Brain Level for NAC Group   [ Time Frame: at 6 months ]

15.  Secondary:   Glutamine Brain Level for Placebo Group   [ Time Frame: at 6 months ]

16.  Secondary:   Glutamate Brain Level for NAC Group   [ Time Frame: at 6 months ]

17.  Secondary:   Glutamate Brain Level for Placebo Group   [ Time Frame: at 6 months ]

18.  Secondary:   Glutathione Brain Level for NAC Group   [ Time Frame: at 6 months ]

19.  Secondary:   Glutathione Brain Level for Placebo Group   [ Time Frame: at 6 months ]

20.  Secondary:   Myo-Inositol Brain Level for the NAC Group   [ Time Frame: at 6 months ]

21.  Secondary:   Myo-Inositol Brain Level for Placebo Group   [ Time Frame: at 6 months ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Larry Seidman, PhD
Organization: Beth Israel Deaconess Medical Center
phone: 617 754-1238
e-mail: lseidman@bidmc.harvard.edu


Publications:

Responsible Party: Larry Seidman, Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier: NCT01354132     History of Changes
Other Study ID Numbers: 2008P000460
107865 ( Other Identifier: FDA IND )
First Submitted: May 13, 2011
First Posted: May 16, 2011
Results First Submitted: March 17, 2017
Results First Posted: June 7, 2017
Last Update Posted: July 5, 2017