Trial Outcomes & Findings for A Pilot Trial of Acute N-Acetylcysteine Effects on Working Memory and Other Cognitive Functions in Schizophrenia (NCT NCT01232790)

NCT ID: NCT01232790

Last Updated: 2015-12-01

Results Overview

The Brief Assessment of Cognition in Schizophrenia (BACS) is an instrument that assesses the aspects of cognition found to be most impaired and most strongly correlated with outcome in patients with schizophrenia. The BACS composite raw score the total of the raw scores for the 6 subtests of the BACS (Verbal memory, token motor, digit sequencing, verbal fluency, symbol coding and executive functioning). The range, so we could be from 0-435. A high score total score is more favorable and indicates a higher level of cognition. The BACS requires less than 35 min to complete in patients with schizophrenia, yields a high completion rate in these patients, and has high reliability. The BACS was found to be as sensitive to cognitive impairment in patients with schizophrenia as a standard battery of tests that required over 2 h to administer. It is the raw sum of the test items and higher scores are favorable.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 28 participants
• Primary outcome timeframe: Baseline
• Results posted on: 2015-12-01

Participant Flow

Participant milestones

Measure	Group A: NAC 1st Trial, Placebo 2nd Trial Group A first receives the commercially available sustained release form of NAC, then the matching placebo capsules both administered at 1200mg twice a day for 3 full days, along with 1200mg once on the evening prior to and once on the morning following the 3 days (8 total doses over 5 days).	Group B: Placebo 1st Trial, NAC 2nd Trial Group B first receives the matching placebo capsules both administered at 1200mg twice a day for 3 full days, along with 1200mg once on the evening prior to and once on the morning following the 3 days , then receives commercially available sustained release form of NAC for the same period (8 total doses over 5 days).
Randomization STARTED	14	14
Randomization COMPLETED	12	12
Randomization NOT COMPLETED	2	2
Initial Assessment STARTED	12	12
Initial Assessment COMPLETED	12	11
Initial Assessment NOT COMPLETED	0	1
First Crossover STARTED	12	11
First Crossover COMPLETED	11	11
First Crossover NOT COMPLETED	1	0
Second Crossover STARTED	11	11
Second Crossover COMPLETED	10	9
Second Crossover NOT COMPLETED	1	2

Reasons for withdrawal

Measure	Group A: NAC 1st Trial, Placebo 2nd Trial Group A first receives the commercially available sustained release form of NAC, then the matching placebo capsules both administered at 1200mg twice a day for 3 full days, along with 1200mg once on the evening prior to and once on the morning following the 3 days (8 total doses over 5 days).	Group B: Placebo 1st Trial, NAC 2nd Trial Group B first receives the matching placebo capsules both administered at 1200mg twice a day for 3 full days, along with 1200mg once on the evening prior to and once on the morning following the 3 days , then receives commercially available sustained release form of NAC for the same period (8 total doses over 5 days).
Randomization Withdrawal by Subject	2	0
Randomization Protocol Violation	0	1
Randomization Physician Decision	0	1
Initial Assessment Withdrawal by Subject	0	1
First Crossover Withdrawal by Subject	1	0
Second Crossover Withdrawal by Subject	1	2

Baseline Characteristics

A Pilot Trial of Acute N-Acetylcysteine Effects on Working Memory and Other Cognitive Functions in Schizophrenia

Baseline characteristics by cohort

Measure	Participants n=28 Participants This is the overall group of trial participants prior to randomization to either of the two crossover arms in the study.
Age, Continuous	48.64 years STANDARD_DEVIATION 10.58 • n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants
Sex: Female, Male Male	20 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline

Population: Subjects analyzed are those with complete data at baseline prior to dropout from the study.

The Brief Assessment of Cognition in Schizophrenia (BACS) is an instrument that assesses the aspects of cognition found to be most impaired and most strongly correlated with outcome in patients with schizophrenia.

The BACS composite raw score the total of the raw scores for the 6 subtests of the BACS (Verbal memory, token motor, digit sequencing, verbal fluency, symbol coding and executive functioning). The range, so we could be from 0-435. A high score total score is more favorable and indicates a higher level of cognition.

The BACS requires less than 35 min to complete in patients with schizophrenia, yields a high completion rate in these patients, and has high reliability. The BACS was found to be as sensitive to cognitive impairment in patients with schizophrenia as a standard battery of tests that required over 2 h to administer. It is the raw sum of the test items and higher scores are favorable.

Outcome measures

Measure	Intervention n=23 Participants This is the combined intervention group (both those receiving the intervention first and those receiving the intervention second).	Placebo n=23 Participants This is the combined placebo group (both those receiving the placebo first and those receiving the placebo second).
BACS Composite RAW Score	229.04 units on a scale Standard Deviation 38.95	227.83 units on a scale Standard Deviation 44.44

PRIMARY outcome

Timeframe: Follow Up (5 days)

Population: Subjects analyzed are those with complete data at follow up and does not include those that had dropped from the study.

The Brief Assessment of Cognition in Schizophrenia (BACS) is an instrument that assesses the aspects of cognition found to be most impaired and most strongly correlated with outcome in patients with schizophrenia.

The BACS composite raw score the total of the raw scores for the 6 subtests of the BACS (Verbal memory, token motor, digit sequencing, verbal fluency, symbol coding and executive functioning). The range, so we could be from 0-435. A high score total score is more favorable and indicates a higher level of cognition.

The BACS requires less than 35 min to complete in patients with schizophrenia, yields a high completion rate in these patients, and has high reliability. The BACS was found to be as sensitive to cognitive impairment in patients with schizophrenia as a standard battery of tests that required over 2 h to administer. It is the raw sum of the test items and higher scores are favorable.

Outcome measures

Measure	Intervention n=21 Participants This is the combined intervention group (both those receiving the intervention first and those receiving the intervention second).	Placebo n=22 Participants This is the combined placebo group (both those receiving the placebo first and those receiving the placebo second).
BACS Composite RAW Score	234.90 units on a scale Standard Deviation 35.15	237.77 units on a scale Standard Deviation 41.37

PRIMARY outcome

Timeframe: Change from Baseline at Follow Up (5 days)

Population: Subjects analyzed are only those with complete data at baseline and 5 day follow up in the study.

The Brief Assessment of Cognition in Schizophrenia (BACS) is an instrument that assesses the aspects of cognition found to be most impaired and most strongly correlated with outcome in patients with schizophrenia.

The BACS composite raw score the total of the raw scores for the 6 subtests of the BACS (Verbal memory, token motor, digit sequencing, verbal fluency, symbol coding and executive functioning). The range, so we could be from 0-435. A high score total score is more favorable and indicates a higher level of cognition.

The BACS requires less than 35 min to complete in patients with schizophrenia, yields a high completion rate in these patients, and has high reliability. The BACS was found to be as sensitive to cognitive impairment in patients with schizophrenia as a standard battery of tests that required over 2 h to administer. It is the raw sum of the test items and higher scores are favorable.

Outcome measures

Measure	Intervention n=21 Participants This is the combined intervention group (both those receiving the intervention first and those receiving the intervention second).	Placebo n=22 Participants This is the combined placebo group (both those receiving the placebo first and those receiving the placebo second).
BACS Composite RAW Score	-7.00 units on a scale Standard Deviation 13.89	-5.59 units on a scale Standard Deviation 13.63

PRIMARY outcome

Timeframe: Baseline 1st Leg of Crossover

Population: Subjects analyzed are those with complete data at baseline prior to dropout from the study.

The Brief Assessment of Cognition in Schizophrenia (BACS) is an instrument that assesses the aspects of cognition found to be most impaired and most strongly correlated with outcome in patients with schizophrenia.

The BACS composite raw score the total of the raw scores for the 6 subtests of the BACS (Verbal memory, token motor, digit sequencing, verbal fluency, symbol coding and executive functioning). The range, so we could be from 0-435. A high score total score is more favorable and indicates a higher level of cognition.

The BACS requires less than 35 min to complete in patients with schizophrenia, yields a high completion rate in these patients, and has high reliability. The BACS was found to be as sensitive to cognitive impairment in patients with schizophrenia as a standard battery of tests that required over 2 h to administer. It is the raw sum of the test items and higher scores are favorable.

Outcome measures

Measure	Intervention n=12 Participants This is the combined intervention group (both those receiving the intervention first and those receiving the intervention second).	Placebo n=11 Participants This is the combined placebo group (both those receiving the placebo first and those receiving the placebo second).
BACS Composite RAW Score	222.75 units on a scale Standard Deviation 40.72	226.45 units on a scale Standard Deviation 34.73

PRIMARY outcome

Timeframe: Follow Up 1st Leg of Crossover (5 Days)

Population: Per protocol

The Brief Assessment of Cognition in Schizophrenia (BACS) is an instrument that assesses the aspects of cognition found to be most impaired and most strongly correlated with outcome in patients with schizophrenia.

The BACS composite raw score the total of the raw scores for the 6 subtests of the BACS (Verbal memory, token motor, digit sequencing, verbal fluency, symbol coding and executive functioning). The range, so we could be from 0-435. A high score total score is more favorable and indicates a higher level of cognition.

The BACS requires less than 35 min to complete in patients with schizophrenia, yields a high completion rate in these patients, and has high reliability. The BACS was found to be as sensitive to cognitive impairment in patients with schizophrenia as a standard battery of tests that required over 2 h to administer. It is the raw sum of the test items and higher scores are favorable.

Outcome measures

Measure	Intervention n=12 Participants This is the combined intervention group (both those receiving the intervention first and those receiving the intervention second).	Placebo n=11 Participants This is the combined placebo group (both those receiving the placebo first and those receiving the placebo second).
BACS Composite RAW Score	231.58 units on a scale Standard Deviation 43.25	237.00 units on a scale Standard Deviation 37.62

PRIMARY outcome

Timeframe: Baseline 2nd Leg of Crossover

Population: Subjects analyzed are those with complete data at baseline prior to dropout from the study.

The Brief Assessment of Cognition in Schizophrenia (BACS) is an instrument that assesses the aspects of cognition found to be most impaired and most strongly correlated with outcome in patients with schizophrenia.

The BACS composite raw score the total of the raw scores for the 6 subtests of the BACS (Verbal memory, token motor, digit sequencing, verbal fluency, symbol coding and executive functioning). The range, so we could be from 0-435. A high score total score is more favorable and indicates a higher level of cognition.

The BACS requires less than 35 min to complete in patients with schizophrenia, yields a high completion rate in these patients, and has high reliability. The BACS was found to be as sensitive to cognitive impairment in patients with schizophrenia as a standard battery of tests that required over 2 h to administer. It is the raw sum of the test items and higher scores are favorable.

Outcome measures

Measure	Intervention n=12 Participants This is the combined intervention group (both those receiving the intervention first and those receiving the intervention second).	Placebo n=11 Participants This is the combined placebo group (both those receiving the placebo first and those receiving the placebo second).
BACS Composite RAW Score	229.08 units on a scale Standard Deviation 53.38	235.91 units on a scale Standard Deviation 239.33

PRIMARY outcome

Timeframe: Follow Up 2nd Leg of Crossover (5 Days)

Population: Subjects analyzed are those with complete data at follow up and does not include those dropped out from the study.

The Brief Assessment of Cognition in Schizophrenia (BACS) is an instrument that assesses the aspects of cognition found to be most impaired and most strongly correlated with outcome in patients with schizophrenia.

The BACS composite raw score the total of the raw scores for the 6 subtests of the BACS (Verbal memory, token motor, digit sequencing, verbal fluency, symbol coding and executive functioning). The range, so we could be from 0-435. A high score total score is more favorable and indicates a higher level of cognition.

The BACS requires less than 35 min to complete in patients with schizophrenia, yields a high completion rate in these patients, and has high reliability. The BACS was found to be as sensitive to cognitive impairment in patients with schizophrenia as a standard battery of tests that required over 2 h to administer. It is the raw sum of the test items and higher scores are favorable.

Outcome measures

Measure	Intervention n=11 Participants This is the combined intervention group (both those receiving the intervention first and those receiving the intervention second).	Placebo n=9 Participants This is the combined placebo group (both those receiving the placebo first and those receiving the placebo second).
BACS Composite RAW Score	238.55 units on a scale Standard Deviation 46.67	239.33 units on a scale Standard Deviation 21.85

SECONDARY outcome

Timeframe: Baseline

Population: All participants were analyzed that had baseline data collected (including any that did not complete the time frame).

Letter Number Sequencing (LNS) is a brief, standardized executive function task used to assess verbal working memory performance. The test involves a 24-item Experimental Condition, in which participants are read a series of letters and numbers and asked to recite both back in ascending order, with the numbers first and then the letters. Participants receive one point for each correct answer for a range of 0-24. Higher scores are better.

Outcome measures

Measure	Intervention n=23 Participants This is the combined intervention group (both those receiving the intervention first and those receiving the intervention second).	Placebo n=23 Participants This is the combined placebo group (both those receiving the placebo first and those receiving the placebo second).
Letter/Number Sequencing Task Tests for Attention, Concentration & Mental Control (LNS) RAW SCORE.	13.43 units on a scale Standard Deviation 2.76	13.22 units on a scale Standard Deviation 3.15

SECONDARY outcome

Timeframe: Follow Up (5 days)

Population: Subjects analyzed are those with complete data at follow up and does not include those that had dropped from the study.

Letter Number Sequencing (LNS) is a brief, standardized executive function task used to assess verbal working memory performance. The test involves a 24-item Experimental Condition, in which participants are read a series of letters and numbers and asked to recite both back in ascending order, with the numbers first and then the letters. Participants receive one point for each correct answer for a range of 0-24. Higher scores are better.

Outcome measures

Measure	Intervention n=21 Participants This is the combined intervention group (both those receiving the intervention first and those receiving the intervention second).	Placebo n=22 Participants This is the combined placebo group (both those receiving the placebo first and those receiving the placebo second).
Letter/Number Sequencing Task Tests for Attention, Concentration & Mental Control (LNS) RAW SCORE.	13.48 units on a scale Standard Deviation 3.15	13.81 units on a scale Standard Deviation 3.49

SECONDARY outcome

Timeframe: Change from Baseline at Follow Up (5 days)

Population: Subjects analyzed are those with complete data at follow up and does not include those that had dropped from the study.

Letter Number Sequencing (LNS) is a brief, standardized executive function task used to assess verbal working memory performance. The test involves a 24-item Experimental Condition, in which participants are read a series of letters and numbers and asked to recite both back in ascending order, with the numbers first and then the letters. Participants receive one point for each correct answer for a range of 0-24. Higher scores are better.

Outcome measures

Measure	Intervention n=21 Participants This is the combined intervention group (both those receiving the intervention first and those receiving the intervention second).	Placebo n=22 Participants This is the combined placebo group (both those receiving the placebo first and those receiving the placebo second).
Letter/Number Sequencing Task Tests for Attention, Concentration & Mental Control (LNS) RAW SCORE.	0.14 units on a scale Standard Deviation 1.82	-0.45 units on a scale Standard Deviation 2.36

SECONDARY outcome

Timeframe: Baseline 1st Leg of Crossover

Population: Subjects analyzed are those with complete data at baseline prior to dropout from the study.

Letter Number Sequencing (LNS) is a brief, standardized executive function task used to assess verbal working memory performance. The test involves a 24-item Experimental Condition, in which participants are read a series of letters and numbers and asked to recite both back in ascending order, with the numbers first and then the letters. Participants receive one point for each correct answer for a range of 0-24. Higher scores are better.

Outcome measures

Measure	Intervention n=12 Participants This is the combined intervention group (both those receiving the intervention first and those receiving the intervention second).	Placebo n=11 Participants This is the combined placebo group (both those receiving the placebo first and those receiving the placebo second).
Letter/Number Sequencing Task Tests for Attention, Concentration & Mental Control (LNS) RAW SCORE.	13.33 units on a scale Standard Deviation 2.84	13.00 units on a scale Standard Deviation 3.35

SECONDARY outcome

Timeframe: Follow Up 1st Leg of Crossover (5 Days)

Population: Subjects analyzed are those with complete data at follow up and does not include those that had dropped from the study.

Letter Number Sequencing (LNS) is a brief, standardized executive function task used to assess verbal working memory performance. The test involves a 24-item Experimental Condition, in which participants are read a series of letters and numbers and asked to recite both back in ascending order, with the numbers first and then the letters. Participants receive one point for each correct answer for a range of 0-24. Higher scores are better.

Outcome measures

Measure	Intervention n=12 Participants This is the combined intervention group (both those receiving the intervention first and those receiving the intervention second).	Placebo n=11 Participants This is the combined placebo group (both those receiving the placebo first and those receiving the placebo second).
Letter/Number Sequencing Task Tests for Attention, Concentration & Mental Control (LNS) RAW SCORE.	12.75 units on a scale Standard Deviation 2.41	13.36 units on a scale Standard Deviation 3.67

SECONDARY outcome

Timeframe: Baseline 2nd Leg of Crossover

Population: Subjects analyzed are those with complete data at 2nd baseline in the crossover and could include those that had dropped from the study if data was collected prior to drop out.

Letter Number Sequencing (LNS) is a brief, standardized executive function task used to assess verbal working memory performance. The test involves a 24-item Experimental Condition, in which participants are read a series of letters and numbers and asked to recite both back in ascending order, with the numbers first and then the letters. Participants receive one point for each correct answer for a range of 0-24. Higher scores are better.

Outcome measures

Measure	Intervention n=12 Participants This is the combined intervention group (both those receiving the intervention first and those receiving the intervention second).	Placebo n=11 Participants This is the combined placebo group (both those receiving the placebo first and those receiving the placebo second).
Letter/Number Sequencing Task Tests for Attention, Concentration & Mental Control (LNS) RAW SCORE.	13.42 units on a scale Standard Deviation 3.08	13.55 units on a scale Standard Deviation 2.81

SECONDARY outcome

Timeframe: Follow Up 2nd Leg of Crossover (5 Days)

Population: Subjects analyzed are those with complete data at 2nd follow up in the crossover and does not include those that had dropped from the study.

Letter Number Sequencing (LNS) is a brief, standardized executive function task used to assess verbal working memory performance. The test involves a 24-item Experimental Condition, in which participants are read a series of letters and numbers and asked to recite both back in ascending order, with the numbers first and then the letters. Participants receive one point for each correct answer for a range of 0-24. Higher scores are better.

Outcome measures

Measure	Intervention n=11 Participants This is the combined intervention group (both those receiving the intervention first and those receiving the intervention second).	Placebo n=9 Participants This is the combined placebo group (both those receiving the placebo first and those receiving the placebo second).
Letter/Number Sequencing Task Tests for Attention, Concentration & Mental Control (LNS) RAW SCORE.	14.27 units on a scale Standard Deviation 3.41	14.44 units on a scale Standard Deviation 1.51

SECONDARY outcome

Timeframe: Baseline

Population: All participants were analyzed that had baseline data collected (including any that did not complete the time frame).

Brief Visuospatial Memory Test (BVMT) is a measure of visuospatial memory. This task includes three trials of six geometric figures printed in a 2 x 3 array on separate pages. The respondent views the stimulus page for 10 seconds and is asked to draw as many of the figures as possible in their correct location on a page in the response booklet. A Delayed Recall Trial is administered after a 25-minute delay. Scoring is based on accuracy of the figure as well as its location on the page. A range of 0-12 per trial is possible(0-36 total). Higher scores are better.

Outcome measures

Measure	Intervention n=23 Participants This is the combined intervention group (both those receiving the intervention first and those receiving the intervention second).	Placebo n=23 Participants This is the combined placebo group (both those receiving the placebo first and those receiving the placebo second).
Brief Visuospatial Memory Test (BVMT) RAW SCORE.	20.35 units on a scale Standard Deviation 6.29	20.65 units on a scale Standard Deviation 7.87

SECONDARY outcome

Timeframe: Follow Up (5 days)

Population: Subjects analyzed are those with complete data at follow up in the crossover and does not include those that had dropped from the study.

Brief Visuospatial Memory Test (BVMT) is a measure of visuospatial memory. This task includes three trials of six geometric figures printed in a 2 x 3 array on separate pages. The respondent views the stimulus page for 10 seconds and is asked to draw as many of the figures as possible in their correct location on a page in the response booklet. A Delayed Recall Trial is administered after a 25-minute delay. Scoring is based on accuracy of the figure as well as its location on the page. A range of 0-12 per trial is possible(0-36 total). Higher scores are better.

Outcome measures

Measure	Intervention n=21 Participants This is the combined intervention group (both those receiving the intervention first and those receiving the intervention second).	Placebo n=22 Participants This is the combined placebo group (both those receiving the placebo first and those receiving the placebo second).
Brief Visuospatial Memory Test (BVMT) RAW SCORE.	17.90 units on a scale Standard Deviation 6.29	17.68 units on a scale Standard Deviation 5.86

SECONDARY outcome

Timeframe: Change from Baseline at Follow Up (Baseline - Follow Up)

Population: Subjects analyzed are those with complete data at all timepoints and does not include those that had dropped from the study.

Brief Visuospatial Memory Test (BVMT) is a measure of visuospatial memory. This task includes three trials of six geometric figures printed in a 2 x 3 array on separate pages. The respondent views the stimulus page for 10 seconds and is asked to draw as many of the figures as possible in their correct location on a page in the response booklet. A Delayed Recall Trial is administered after a 25-minute delay. Scoring is based on accuracy of the figure as well as its location on the page. A range of 0-12 per trial is possible(0-36 total). Higher scores are better.

Outcome measures

Measure	Intervention n=21 Participants This is the combined intervention group (both those receiving the intervention first and those receiving the intervention second).	Placebo n=22 Participants This is the combined placebo group (both those receiving the placebo first and those receiving the placebo second).
Brief Visuospatial Memory Test (BVMT) RAW SCORE.	2.57 units on a scale Standard Deviation 5.13	2.77 units on a scale Standard Deviation 5.76

SECONDARY outcome

Timeframe: Baseline 1st Leg of Crossover

Population: Per protocol

Brief Visuospatial Memory Test (BVMT) is a measure of visuospatial memory. This task includes three trials of six geometric figures printed in a 2 x 3 array on separate pages. The respondent views the stimulus page for 10 seconds and is asked to draw as many of the figures as possible in their correct location on a page in the response booklet. A Delayed Recall Trial is administered after a 25-minute delay. Scoring is based on accuracy of the figure as well as its location on the page. A range of 0-12 per trial is possible(0-36 total). Higher scores are better.

Outcome measures

Measure	Intervention n=12 Participants This is the combined intervention group (both those receiving the intervention first and those receiving the intervention second).	Placebo n=11 Participants This is the combined placebo group (both those receiving the placebo first and those receiving the placebo second).
Brief Visuospatial Memory Test (BVMT) RAW SCORE.	20.67 units on a scale Standard Deviation 5.82	19.73 units on a scale Standard Deviation 16.55

SECONDARY outcome

Timeframe: Follow Up 1st Leg of Crossover (5 Days)

Population: Per protocol

Brief Visuospatial Memory Test (BVMT) is a measure of visuospatial memory. This task includes three trials of six geometric figures printed in a 2 x 3 array on separate pages. The respondent views the stimulus page for 10 seconds and is asked to draw as many of the figures as possible in their correct location on a page in the response booklet. A Delayed Recall Trial is administered after a 25-minute delay. Scoring is based on accuracy of the figure as well as its location on the page. A range of 0-12 per trial is possible(0-36 total). Higher scores are better.

Outcome measures

Measure	Intervention n=12 Participants This is the combined intervention group (both those receiving the intervention first and those receiving the intervention second).	Placebo n=11 Participants This is the combined placebo group (both those receiving the placebo first and those receiving the placebo second).
Brief Visuospatial Memory Test (BVMT) RAW SCORE.	16.55 units on a scale Standard Deviation 6.07	18.25 units on a scale Standard Deviation 7.39

SECONDARY outcome

Timeframe: Baseline 2nd Leg of Crossover

Population: Subjects analyzed are those with complete data at 2nd baseline in the crossover and could include those that had dropped from the study if data was collected prior to drop out.

Brief Visuospatial Memory Test (BVMT) is a measure of visuospatial memory. This task includes three trials of six geometric figures printed in a 2 x 3 array on separate pages. The respondent views the stimulus page for 10 seconds and is asked to draw as many of the figures as possible in their correct location on a page in the response booklet. A Delayed Recall Trial is administered after a 25-minute delay. Scoring is based on accuracy of the figure as well as its location on the page. A range of 0-12 per trial is possible(0-36 total). Higher scores are better.

Outcome measures

Measure	Intervention n=12 Participants This is the combined intervention group (both those receiving the intervention first and those receiving the intervention second).	Placebo n=11 Participants This is the combined placebo group (both those receiving the placebo first and those receiving the placebo second).
Brief Visuospatial Memory Test (BVMT) RAW SCORE.	21.50 units on a scale Standard Deviation 7.80	20.00 units on a scale Standard Deviation 7.01

SECONDARY outcome

Timeframe: Follow Up 2nd Leg of Crossover (5 Days)

Population: Per protocol

Brief Visuospatial Memory Test (BVMT) is a measure of visuospatial memory. This task includes three trials of six geometric figures printed in a 2 x 3 array on separate pages. The respondent views the stimulus page for 10 seconds and is asked to draw as many of the figures as possible in their correct location on a page in the response booklet. A Delayed Recall Trial is administered after a 25-minute delay. Scoring is based on accuracy of the figure as well as its location on the page. A range of 0-12 per trial is possible(0-36 total). Higher scores are better.

Outcome measures

Measure	Intervention n=11 Participants This is the combined intervention group (both those receiving the intervention first and those receiving the intervention second).	Placebo n=9 Participants This is the combined placebo group (both those receiving the placebo first and those receiving the placebo second).
Brief Visuospatial Memory Test (BVMT) RAW SCORE.	18.82 units on a scale Standard Deviation 5.69	17.44 units on a scale Standard Deviation 4.85

SECONDARY outcome

Timeframe: Pre Screening

Population: Per protocol

Brief Psychiatric Rating Scale (BPRS) utilized before and after treatment. BPRS total score is a total of the 18 item scores with a range of 18-126. It is used to measure schizophrenia symptoms and to assess change in them over time. There are 18 symptom sub scores. Each symptom is rated 1-7 (not present to extremely severe) and then all items are summed for the total score. Higher scores indicate more severe symptoms.

The BPRS is the gold-standard overall measure of schizophrenia symptoms which will be utilized to demonstrate that the intervention does not cause worsening of the illness symptoms apart from the usual fluctuations of the natural course.

Outcome measures

Measure	Intervention n=12 Participants This is the combined intervention group (both those receiving the intervention first and those receiving the intervention second).	Placebo n=12 Participants This is the combined placebo group (both those receiving the placebo first and those receiving the placebo second).
Brief Psychiatric Rating Scale (BPRS)Total Score	30.92 units on a scale Standard Deviation 7.20	28.41 units on a scale Standard Deviation 7.41

SECONDARY outcome

Timeframe: End of Trial

Population: Per protocol

Brief Psychiatric Rating Scale (BPRS) utilized before and after treatment. BPRS total score is a total of the 18 item scores with a range of 18-126. It is used to measure schizophrenia symptoms and to assess change in them over time. There are 18 symptom sub scores. Each symptom is rated 1-7 (not present to extremely severe) and then all items are summed for the total score. Higher scores indicate more severe symptoms.

The BPRS is the gold-standard overall measure of schizophrenia symptoms which will be utilized to demonstrate that the intervention does not cause worsening of the illness symptoms apart from the usual fluctuations of the natural course.

Outcome measures

Measure	Intervention n=10 Participants This is the combined intervention group (both those receiving the intervention first and those receiving the intervention second).	Placebo n=9 Participants This is the combined placebo group (both those receiving the placebo first and those receiving the placebo second).
Brief Psychiatric Rating Scale (BPRS)Total Score	32.80 units on a scale Standard Deviation 7.31	27.78 units on a scale Standard Deviation 8.91

SECONDARY outcome

Timeframe: Change from PreScreening at End of Trial

Population: Analyses only used matched cases and does not include participants with incomplete data.

Brief Psychiatric Rating Scale (BPRS) utilized before and after treatment. BPRS total score is a total of the 18 item scores with a range of 18-126. It is used to measure schizophrenia symptoms and to assess change in them over time. There are 18 symptom sub scores. Each symptom is rated 1-7 (not present to extremely severe) and then all items are summed for the total score. Higher scores indicate more severe symptoms.

The BPRS is the gold-standard overall measure of schizophrenia symptoms which will be utilized to demonstrate that the intervention does not cause worsening of the illness symptoms apart from the usual fluctuations of the natural course.

Outcome measures

Measure	Intervention n=10 Participants This is the combined intervention group (both those receiving the intervention first and those receiving the intervention second).	Placebo n=9 Participants This is the combined placebo group (both those receiving the placebo first and those receiving the placebo second).
Brief Psychiatric Rating Scale (BPRS)Total Score	1.70 units on a scale Standard Deviation 2.36	0.89 units on a scale Standard Deviation 1.05

Adverse Events

Placebo: First Crossover Follow Up

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

NAC: First Crossover Follow Up

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Placebo: Second Crossover Follow Up

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

NAC: Second Crossover Follow Up

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Placebo: First Crossover Follow Up n=11 participants at risk This group of participants received the placebo on the first day in the crossover design.	NAC: First Crossover Follow Up n=12 participants at risk This group of participants received the active treatment (NAC) on the first day of the crossover study.	Placebo: Second Crossover Follow Up n=11 participants at risk This group of participants received the placebo on the second day in the crossover design.	NAC: Second Crossover Follow Up n=11 participants at risk This group of participants received the active treatment (NAC) on the second day of the crossover study.
Nervous system disorders Headache	0.00% 0/11	8.3% 1/12 • Number of events 1	0.00% 0/11	9.1% 1/11 • Number of events 1
Gastrointestinal disorders Nausea	27.3% 3/11 • Number of events 4	8.3% 1/12 • Number of events 1	0.00% 0/11	9.1% 1/11 • Number of events 1
Metabolism and nutrition disorders Appetite Loss	0.00% 0/11	8.3% 1/12 • Number of events 1	0.00% 0/11	0.00% 0/11
Gastrointestinal disorders Constipation	0.00% 0/11	0.00% 0/12	0.00% 0/11	9.1% 1/11 • Number of events 1
Gastrointestinal disorders Diarrhea	0.00% 0/11	8.3% 1/12 • Number of events 1	0.00% 0/11	0.00% 0/11
General disorders Drowsiness	9.1% 1/11 • Number of events 1	8.3% 1/12 • Number of events 1	0.00% 0/11	0.00% 0/11
Metabolism and nutrition disorders Weight Gain	0.00% 0/11	8.3% 1/12 • Number of events 1	9.1% 1/11 • Number of events 1	0.00% 0/11
Gastrointestinal disorders Heartburn	0.00% 0/11	8.3% 1/12 • Number of events 1	9.1% 1/11 • Number of events 1	0.00% 0/11
General disorders Libido Increase	9.1% 1/11 • Number of events 1	0.00% 0/12	0.00% 0/11	9.1% 1/11 • Number of events 1
General disorders Sleep Disturbance	9.1% 1/11 • Number of events 1	16.7% 2/12 • Number of events 3	0.00% 0/11	0.00% 0/11
Nervous system disorders Memory Loss	0.00% 0/11	8.3% 1/12 • Number of events 1	9.1% 1/11 • Number of events 1	0.00% 0/11
General disorders Nasal Congestion	0.00% 0/11	8.3% 1/12 • Number of events 1	9.1% 1/11 • Number of events 1	0.00% 0/11
Nervous system disorders Dizzyness	0.00% 0/11	8.3% 1/12 • Number of events 1	0.00% 0/11	0.00% 0/11

Additional Information

Cenk Tek MD, Associate Professor of Psychiatry; Director, Psychosis Program, CMHC

Yale University School of Medicine, Department of Psychiatry

Phone: (203) 974-7484

Email: cenk.tek@yale.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place