Trial Outcomes & Findings for N-Acetyl-Cysteine (NAC) in Early Phase Schizophrenia Spectrum Psychosis (NCT NCT01354132)

Last Updated: 2017-07-05

Results Overview

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 .

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

20 participants

Primary outcome timeframe

at 6 months

Results posted on

2017-07-05

Participant Flow

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

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

Participant milestones

Participant milestones
Measure	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
Randomization STARTED	32	31
Randomization COMPLETED	31	30
Randomization NOT COMPLETED	1	1
Double Blind (Visits 1-7) STARTED	31	30
Double Blind (Visits 1-7) Completed More Than 1 Visit	4	5
Double Blind (Visits 1-7) Stopped After First Visit	3	2
Double Blind (Visits 1-7) Didn't Complete at Least 1 Visit	2	4
Double Blind (Visits 1-7) COMPLETED	22	19
Double Blind (Visits 1-7) NOT COMPLETED	9	11
1 Month Post Study Medication STARTED	22	19
1 Month Post Study Medication 1 Follow-up Visit (Visit 8)	21	16
1 Month Post Study Medication COMPLETED	21	16
1 Month Post Study Medication NOT COMPLETED	1	3

Reasons for withdrawal

Reasons for withdrawal
Measure	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
Randomization Physician Decision	1	0
Randomization Withdrawal by Subject	0	1
Double Blind (Visits 1-7) Adverse Event	1	0
Double Blind (Visits 1-7) Withdrawal by Subject	8	11
1 Month Post Study Medication Withdrawal by Subject	1	3

Baseline Characteristics

Numbers in each group analyzed based on those who completed baseline and post testing.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	N-acetyl-cysteine n=31 Participants 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 n=30 Participants 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 n=61 Participants Total of all reporting groups
Age, Continuous	26.1 years STANDARD_DEVIATION 6.1 • n=31 Participants	24.7 years STANDARD_DEVIATION 5.9 • n=30 Participants	25.4 years STANDARD_DEVIATION 6.0 • n=61 Participants
Sex: Female, Male Female	5 Participants n=31 Participants	9 Participants n=30 Participants	14 Participants n=61 Participants
Sex: Female, Male Male	26 Participants n=31 Participants	21 Participants n=30 Participants	47 Participants n=61 Participants
Race/Ethnicity, Customized Black or African American	5 Participants n=31 Participants	7 Participants n=30 Participants	12 Participants n=61 Participants
Race/Ethnicity, Customized White	25 Participants n=31 Participants	22 Participants n=30 Participants	47 Participants n=61 Participants
Race/Ethnicity, Customized Maghreb	1 Participants n=31 Participants	1 Participants n=30 Participants	2 Participants n=61 Participants
Race/Ethnicity, Customized Hispanic or Latino	0 Participants n=31 Participants	1 Participants n=30 Participants	1 Participants n=61 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	31 Participants n=31 Participants	29 Participants n=30 Participants	60 Participants n=61 Participants
Region of Enrollment United States	6 Participants n=31 Participants	4 Participants n=30 Participants	10 Participants n=61 Participants
Region of Enrollment Switzerland	26 Participants n=31 Participants	27 Participants n=30 Participants	53 Participants n=61 Participants
Positive and Negative Symptom Scale (PANSS) Positive PANSS Symptoms	14.3 units on a scale STANDARD_DEVIATION 5.4 • n=31 Participants	15.0 units on a scale STANDARD_DEVIATION 5.6 • n=30 Participants	14.7 units on a scale STANDARD_DEVIATION 16.4 • n=61 Participants
Positive and Negative Symptom Scale (PANSS) Negative Symptoms	15.6 units on a scale STANDARD_DEVIATION 5.0 • n=31 Participants	17.3 units on a scale STANDARD_DEVIATION 6.3 • n=30 Participants	16.4 units on a scale STANDARD_DEVIATION 5.7 • n=61 Participants
Global Assessment of Functioning (GAF)	54 units on a scale STANDARD_DEVIATION 10.8 • n=31 Participants	51.6 units on a scale STANDARD_DEVIATION 12.8 • n=30 Participants	52.8 units on a scale STANDARD_DEVIATION 11.8 • n=61 Participants
Duration of Psychosis	848 days STANDARD_DEVIATION 767 • n=31 Participants	747 days STANDARD_DEVIATION 693 • n=30 Participants	796 days STANDARD_DEVIATION 726 • n=61 Participants
Social and Occupational Functioning Assessment Scale (SOFAS)	55.8 units on a scale STANDARD_DEVIATION 11.0 • n=31 Participants	53.5 units on a scale STANDARD_DEVIATION 13.0 • n=30 Participants	54.7 units on a scale STANDARD_DEVIATION 12.0 • n=61 Participants
MATRICS Consensus Cognitive Battery (MCCB) excluding MISCEIT managing emotions test) Processing Speed	37.72 Standardized T Scores STANDARD_DEVIATION 11.22 • n=20 Participants • Numbers in each group analyzed based on those who completed baseline and post testing.	35.53 Standardized T Scores STANDARD_DEVIATION 16.31 • n=16 Participants • Numbers in each group analyzed based on those who completed baseline and post testing.	36.75 Standardized T Scores STANDARD_DEVIATION 13.48 • n=36 Participants • Numbers in each group analyzed based on those who completed baseline and post testing.
MATRICS Consensus Cognitive Battery (MCCB) excluding MISCEIT managing emotions test) Sustained Attention	40.23 Standardized T Scores STANDARD_DEVIATION 11.71 • n=20 Participants • Numbers in each group analyzed based on those who completed baseline and post testing.	32.67 Standardized T Scores STANDARD_DEVIATION 13.15 • n=16 Participants • Numbers in each group analyzed based on those who completed baseline and post testing.	36.87 Standardized T Scores STANDARD_DEVIATION 12.35 • n=36 Participants • Numbers in each group analyzed based on those who completed baseline and post testing.
MATRICS Consensus Cognitive Battery (MCCB) excluding MISCEIT managing emotions test) Working Memory	47.56 Standardized T Scores STANDARD_DEVIATION 9.70 • n=20 Participants • Numbers in each group analyzed based on those who completed baseline and post testing.	38.87 Standardized T Scores STANDARD_DEVIATION 15.09 • n=16 Participants • Numbers in each group analyzed based on those who completed baseline and post testing.	43.70 Standardized T Scores STANDARD_DEVIATION 12.10 • n=36 Participants • Numbers in each group analyzed based on those who completed baseline and post testing.
MATRICS Consensus Cognitive Battery (MCCB) excluding MISCEIT managing emotions test) Verbal Learning	40.94 Standardized T Scores STANDARD_DEVIATION 10.09 • n=20 Participants • Numbers in each group analyzed based on those who completed baseline and post testing.	40.93 Standardized T Scores STANDARD_DEVIATION 13.73 • n=16 Participants • Numbers in each group analyzed based on those who completed baseline and post testing.	40.94 Standardized T Scores STANDARD_DEVIATION 11.71 • n=36 Participants • Numbers in each group analyzed based on those who completed baseline and post testing.
MATRICS Consensus Cognitive Battery (MCCB) excluding MISCEIT managing emotions test) Visual Learning	41.06 Standardized T Scores STANDARD_DEVIATION 10.01 • n=20 Participants • Numbers in each group analyzed based on those who completed baseline and post testing.	44.86 Standardized T Scores STANDARD_DEVIATION 14.42 • n=16 Participants • Numbers in each group analyzed based on those who completed baseline and post testing.	42.75 Standardized T Scores STANDARD_DEVIATION 11.97 • n=36 Participants • Numbers in each group analyzed based on those who completed baseline and post testing.
MATRICS Consensus Cognitive Battery (MCCB) excluding MISCEIT managing emotions test) Problem Solving	48.00 Standardized T Scores STANDARD_DEVIATION 11.69 • n=20 Participants • Numbers in each group analyzed based on those who completed baseline and post testing.	39.93 Standardized T Scores STANDARD_DEVIATION 12.76 • n=16 Participants • Numbers in each group analyzed based on those who completed baseline and post testing.	44.41 Standardized T Scores STANDARD_DEVIATION 12.17 • n=36 Participants • Numbers in each group analyzed based on those who completed baseline and post testing.
Antipsychotic Medication Chlorpromazine Equivalents	309 milligrams STANDARD_DEVIATION 252 • n=31 Participants	309 milligrams STANDARD_DEVIATION 188 • n=30 Participants	309 milligrams STANDARD_DEVIATION 220 • n=61 Participants
Blood Marker - Cysteine	261.3 uM (micrometer) STANDARD_DEVIATION 37.6 • n=31 Participants	254.0 uM (micrometer) STANDARD_DEVIATION 33.6 • n=30 Participants	257.7 uM (micrometer) STANDARD_DEVIATION 35.7 • n=61 Participants
Blood Marker - GPxbc- Glutathione peroxidase	21.24 umol/min/gHb STANDARD_DEVIATION 7.5 • n=31 Participants	21.01 umol/min/gHb STANDARD_DEVIATION 6.93 • n=30 Participants	21.13 umol/min/gHb STANDARD_DEVIATION 7.17 • n=61 Participants
Blood Marker - Glutathione	0.77 mM (millimolar) in blood cells STANDARD_DEVIATION 0.21 • n=31 Participants	0.84 mM (millimolar) in blood cells STANDARD_DEVIATION 0.27 • n=30 Participants	0.81 mM (millimolar) in blood cells STANDARD_DEVIATION 0.24 • n=61 Participants
Brain Marker - Glutamine and myo-Inositol Glutamine	3.25 mM (millimolar) STANDARD_DEVIATION 0.51 • n=13 Participants • MRS was completed on fewer participants.	2.93 mM (millimolar) STANDARD_DEVIATION 0.48 • n=12 Participants • MRS was completed on fewer participants.	3.10 mM (millimolar) STANDARD_DEVIATION 0.50 • n=25 Participants • MRS was completed on fewer participants.
Brain Marker - Glutamine and myo-Inositol Myo-Inositol	6.25 mM (millimolar) STANDARD_DEVIATION 1.05 • n=13 Participants • MRS was completed on fewer participants.	6.28 mM (millimolar) STANDARD_DEVIATION 0.62 • n=12 Participants • MRS was completed on fewer participants.	6.26 mM (millimolar) STANDARD_DEVIATION 0.84 • n=25 Participants • MRS was completed on fewer participants.
Brain Marker - Glutathione and Glutamate Glutathione	0.87 mM (millimolar) STANDARD_DEVIATION 0.23 • n=13 Participants • Only 25 participants had the MRS.	1.12 mM (millimolar) STANDARD_DEVIATION 0.18 • n=12 Participants • Only 25 participants had the MRS.	0.99 mM (millimolar) STANDARD_DEVIATION 0.21 • n=25 Participants • Only 25 participants had the MRS.
Brain Marker - Glutathione and Glutamate Glutamate	10.12 mM (millimolar) STANDARD_DEVIATION 0.80 • n=13 Participants • Only 25 participants had the MRS.	10.64 mM (millimolar) STANDARD_DEVIATION 1.23 • n=12 Participants • Only 25 participants had the MRS.	10.37 mM (millimolar) STANDARD_DEVIATION 1.01 • n=25 Participants • Only 25 participants had the MRS.

PRIMARY outcome

Timeframe: at 6 months

Population: Analysis was done with those who completed the 6 month treatment protocol.

Outcome measures

Outcome measures
Measure	N-acetyl-cysteine n=22 Participants 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 n=19 Participants 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
Change in Negative Symptoms of Schizophrenia as Measured on the PANSS	16.9 units on a scale Standard Deviation 4.9	17.2 units on a scale Standard Deviation 5.4

SECONDARY outcome

Timeframe: at 6 months

Population: Analysis was done with participants who completed the 6 month treatment phase

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 .

Outcome measures

Outcome measures
Measure	N-acetyl-cysteine n=22 Participants 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 n=19 Participants 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
Change in Positive Symptoms (PANSS)	13.7 units on a scale Standard Deviation 7.8	12.5 units on a scale Standard Deviation 4.6

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	N-acetyl-cysteine n=22 Participants 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 n=19 Participants 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
Global Assessment of Functioning (GAF)	52.2 units on a scale Standard Deviation 11.7	53.8 units on a scale Standard Deviation 11.6

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	N-acetyl-cysteine n=22 Participants 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 n=19 Participants 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
Social and Occupational Functioning Assessment Scale (SOFAS)	54.6 units on a scale Standard Deviation 11.3	54.8 units on a scale Standard Deviation 10.8

SECONDARY outcome

Timeframe: at 6 months

Population: Analysis of cognitive data is based on those who completed the cognitive testing at 6 months which required a separate clinic appointment and thus the overall number of participants is lower due to a loss of that data from failure to keep the cognitive testing appointment.

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.

Outcome measures

Outcome measures
Measure	N-acetyl-cysteine n=20 Participants 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 n=16 Participants 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
Change in Cognition and Working Memory (MATRICS) Speed of Processing	41.47 T- Scores Standard Deviation 11.45	35.85 T- Scores Standard Deviation 14.40

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	N-acetyl-cysteine n=20 Participants 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 n=16 Participants 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
Change in Cognition and Working Memory (MATRICS) Working Memory	47.47 T- Scores Standard Deviation 9.61	38.08 T- Scores Standard Deviation 17.70

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	N-acetyl-cysteine n=20 Participants 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 n=16 Participants 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
Change in Cognition and Working Memory (MATRICS) Attention and Vigilance	40.92 T- Scores Standard Deviation 12.98	30.40 T- Scores Standard Deviation 13.91

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	N-acetyl-cysteine n=20 Participants 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 n=16 Participants 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
Change in Cognition and Working Memory (MATRICS) Verbal Learning	42.18 T- Scores Standard Deviation 10.36	44.62 T- Scores Standard Deviation 12.34

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	N-acetyl-cysteine n=20 Participants 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 n=16 Participants 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
Change in Cognition and Working Memory (MATRICS) Visual Learning	46.00 T- Scores Standard Deviation 9.28	47.75 T- Scores Standard Deviation 19.12

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	N-acetyl-cysteine n=20 Participants 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 n=16 Participants 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
Change in Cognition and Working Memory (MATRICS) Reasoning and Problem Solving	51.13 T- Scores Standard Deviation 10.16	44.38 T- Scores Standard Deviation 12.80

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	N-acetyl-cysteine n=22 Participants 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 n=19 Participants 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
Change in Blood Level of Glutathione	0.92 mM Standard Deviation 0.42	0.82 mM Standard Deviation 0.19

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	N-acetyl-cysteine n=22 Participants 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 n=19 Participants 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
Blood Plasma Level of Cysteine	229.6 uM Standard Deviation 62.9	246.5 uM Standard Deviation 42.4

SECONDARY outcome

Timeframe: 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.