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

This study has been completed.
Sponsor:
Collaborator:
National Alliance for Research on Schizophrenia and Depression
Information provided by (Responsible Party):
Cenk Tek, Yale University
ClinicalTrials.gov Identifier:
NCT01232790
First received: February 25, 2010
Last updated: March 10, 2014
Last verified: March 2014
  Purpose

The purpose of this study is to evaluate the effects of the amino acid supplement N-Acetylcysteine versus placebo on working memory and other cognitive functions in persons with a diagnosis of schizophrenia.


Condition Intervention
Schizophrenia
Dietary Supplement: N-Acetylcysteine

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Pilot Trial of Acute N-Acetylcysteine Effects on Working Memory and Other Cognitive Functions in Schizophrenia

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • BACS Composite RAW Score [ Time Frame: Baseline ] [ Designated as safety issue: No ]

    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.


  • BACS Composite RAW Score [ Time Frame: Follow Up (5 days) ] [ Designated as safety issue: No ]

    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.


  • BACS Composite RAW Score [ Time Frame: Change from Baseline at Follow Up (5 days) ] [ Designated as safety issue: No ]

    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.


  • BACS Composite RAW Score [ Time Frame: Baseline 1st Leg of Crossover ] [ Designated as safety issue: No ]

    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.


  • BACS Composite RAW Score [ Time Frame: Follow Up 1st Leg of Crossover (5 Days) ] [ Designated as safety issue: No ]

    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.


  • BACS Composite RAW Score [ Time Frame: Baseline 2nd Leg of Crossover ] [ Designated as safety issue: No ]

    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.


  • BACS Composite RAW Score [ Time Frame: Follow Up 2nd Leg of Crossover (5 Days) ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • Letter/Number Sequencing Task Tests for Attention, Concentration & Mental Control (LNS) RAW SCORE. [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    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.

  • Letter/Number Sequencing Task Tests for Attention, Concentration & Mental Control (LNS) RAW SCORE. [ Time Frame: Follow Up (5 days) ] [ Designated as safety issue: No ]
    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.

  • Letter/Number Sequencing Task Tests for Attention, Concentration & Mental Control (LNS) RAW SCORE. [ Time Frame: Change from Baseline at Follow Up (5 days) ] [ Designated as safety issue: No ]
    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.

  • Letter/Number Sequencing Task Tests for Attention, Concentration & Mental Control (LNS) RAW SCORE. [ Time Frame: Baseline 1st Leg of Crossover ] [ Designated as safety issue: No ]
    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.

  • Letter/Number Sequencing Task Tests for Attention, Concentration & Mental Control (LNS) RAW SCORE. [ Time Frame: Follow Up 1st Leg of Crossover (5 Days) ] [ Designated as safety issue: No ]
    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.

  • Letter/Number Sequencing Task Tests for Attention, Concentration & Mental Control (LNS) RAW SCORE. [ Time Frame: Baseline 2nd Leg of Crossover ] [ Designated as safety issue: No ]
    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.

  • Letter/Number Sequencing Task Tests for Attention, Concentration & Mental Control (LNS) RAW SCORE. [ Time Frame: Follow Up 2nd Leg of Crossover (5 Days) ] [ Designated as safety issue: No ]
    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.

  • Brief Visuospatial Memory Test (BVMT) RAW SCORE. [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    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.

  • Brief Visuospatial Memory Test (BVMT) RAW SCORE. [ Time Frame: Follow Up (5 days) ] [ Designated as safety issue: No ]
    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.

  • Brief Visuospatial Memory Test (BVMT) RAW SCORE. [ Time Frame: Change from Baseline at Follow Up (Baseline - Follow Up) ] [ Designated as safety issue: No ]
    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.

  • Brief Visuospatial Memory Test (BVMT) RAW SCORE. [ Time Frame: Baseline 1st Leg of Crossover ] [ Designated as safety issue: No ]
    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.

  • Brief Visuospatial Memory Test (BVMT) RAW SCORE. [ Time Frame: Follow Up 1st Leg of Crossover (5 Days) ] [ Designated as safety issue: No ]
    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.

  • Brief Visuospatial Memory Test (BVMT) RAW SCORE. [ Time Frame: Baseline 2nd Leg of Crossover ] [ Designated as safety issue: No ]
    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.

  • Brief Visuospatial Memory Test (BVMT) RAW SCORE. [ Time Frame: Follow Up 2nd Leg of Crossover (5 Days) ] [ Designated as safety issue: No ]
    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.

  • Brief Psychiatric Rating Scale (BPRS)Total Score [ Time Frame: Pre Screening ] [ Designated as safety issue: Yes ]

    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.


  • Brief Psychiatric Rating Scale (BPRS)Total Score [ Time Frame: End of Trial ] [ Designated as safety issue: Yes ]

    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.


  • Brief Psychiatric Rating Scale (BPRS)Total Score [ Time Frame: Change from PreScreening at End of Trial ] [ Designated as safety issue: Yes ]

    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.



Enrollment: 28
Study Start Date: February 2010
Study Completion Date: November 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group A: Intervention/Placebo
Group A first receives the commercially available sustained release form of N-acetylcysteine, 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).
Dietary Supplement: N-Acetylcysteine
N-acetylcysteine 1200mg bid for 3 days
Placebo Comparator: Group B: Placebo/Intervention
Group B first receives the placebo and then receives a commercially available sustained release form of N-Aceytylcysteine. In each arm, the capsules are 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).

Detailed Description:

Working memory impairment in Schizophrenia is produced by deficiencies of feedback inhibition of glutamate release, due to low cysteine-glutamate antiporter activity. Because of this mechanism, we are interested in whether acute administration of N-Acetylcysteine will improve performance of patients with schizophrenia on a battery of cognitive tasks utilized to test working memory and other cognitive domains, versus placebo. This pilot study will utilize a randomized, double blind, placebo controlled, crossover design.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects will be between 18-60
  • Meet DSM-IV criteria for schizophrenia
  • Be on a stable dose of antipsychotic medication for at least 1 month
  • Be deemed clinically stable for 3 months by the regular clinical staff

Exclusion Criteria:

  • Current substance or alcohol abuse
  • Pregnancy
  • Clozapine treatment
  • Known sensitivity to sulphur containing compounds
  • Previous diagnosis of mental retardation
  • Nitroglycerin use
  • Asthma diagnosis, verified and treated by a primary care doctor
  • Use of any other medication that may interact with the study medication
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01232790

Locations
United States, Connecticut
Connecticut Mental Health Center
New Haven, Connecticut, United States, 06519
Sponsors and Collaborators
Yale University
National Alliance for Research on Schizophrenia and Depression
Investigators
Principal Investigator: Cenk Tek, MD Yale University
  More Information

No publications provided

Responsible Party: Cenk Tek, Associate Professor, Yale University
ClinicalTrials.gov Identifier: NCT01232790     History of Changes
Other Study ID Numbers: 0904005039, M131976
Study First Received: February 25, 2010
Results First Received: January 24, 2013
Last Updated: March 10, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Yale University:
Schizophrenia
working memory
N-Acetylcysteine

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Acetylcysteine
N-monoacetylcystine
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Expectorants
Respiratory System Agents
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Antidotes

ClinicalTrials.gov processed this record on September 18, 2014