A Pilot Trial of Acute N-Acetylcysteine Effects on Working Memory and Other Cognitive Functions in Schizophrenia
- Conditions
- Schizophrenia
- Interventions
- Dietary Supplement: N-AcetylcysteineDrug: Placebo
- Registration Number
- NCT01232790
- Lead Sponsor
- Yale University
- Brief Summary
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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 28
- Subjects will be between 18-60
- Meet Diagnostic and Statistical Manual-IV (DSM) 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Group A: Intervention/Placebo N-Acetylcysteine 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). Group B: Placebo/Intervention Placebo Group B first receives the placebo and then receives a commercially available sustained release form of N-Acetylcysteine. 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).
- Primary Outcome Measures
Name Time Method BACS Composite RAW Score Follow Up 2nd Leg of Crossover (5 Days) 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
Name Time Method Letter/Number Sequencing Task Tests for Attention, Concentration & Mental Control (LNS) RAW SCORE. Follow Up 2nd Leg of Crossover (5 Days) 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. Follow Up 2nd Leg of Crossover (5 Days) 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 Change from PreScreening at End of Trial 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.
Trial Locations
- Locations (1)
Connecticut Mental Health Center
🇺🇸New Haven, Connecticut, United States