Gamma-Amino Butyric Acid (GABA)-A Alpha2/3 Study

Phase 2

Completed

Conditions: Schizophrenia

Interventions: Drug: Placebo
Drug: Merck L-830982

Registration Number: NCT00129441

Lead Sponsor: University of Pittsburgh

Brief Summary: The purpose of this research study is to determine whether a short-term administration of an investigational study drug may provide evidence of improvement in cognitive functioning in a group of stable male subjects with schizophrenia.

Detailed Description: The goal of this study is to determine whether the short-term (4 week), double-blind administration of Merck L-830982 provides evidence of improvement in cognitive functioning in stable male subjects with schizophrenia. This initial, small sample size study (n=9 on L-830982 and n=6 on placebo) is restricted to males in order to reduce the variance that might be attributable to the well-documented sex differences in the clinical features of schizophrenia.

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 16

Inclusion Criteria

Male participants
Between the ages of 18 and 50
Meet diagnostic criteria for schizophrenia or schizoaffective disorder
Are clinically stable for a minimum of 3 months on current dose of medication
Are unemployed (i.e., work less than 20 hours per week at competitive employment)

Exclusion Criteria

Psychoactive substance dependence within the past 6 months or substance abuse within the past month
History of head trauma or other neurological disorder
Medical illness or medications, such as benzodiazepine treatment or HIV medications, that may be affected by study participation (the study doctor will discuss this with potential subjects)
Mental retardation
Seizure disorder
History of a heart attack, arrhythmia, or other heart disease

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sugar pill	Placebo	-
Merck L-830982	Merck L-830982	-

Primary Outcome Measures

Name	Time	Method
N-back Task - Reaction Time	Week 4	The N-back task is a sequential-letter memory task for which working memory load is varied, as the respondent must indicate when the current stimulus matches the one from 'n' steps earlier in the sequence. The dependent measure for the N-back task was performance in the 2-back condition, which provides the best index of performance and dorsolateral prefrontal cortex disturbances in subjects with schizophrenia.
N-back Task - Error Rate	Week 4	The N-back task is a sequential-letter memory task for which working memory load is varied, as the respondent must indicate when the current stimulus matches the one from 'n' steps earlier in the sequence. The dependent measure for the N-back task was performance in the 2-back condition, which provides the best index of performance and dorsolateral prefrontal cortex disturbances in subjects with schizophrenia.
AX Continuous Performance Test Task D-prime	Week 4	For the AX Continuous Performance Test, subjects are required to maintain an attentional set across a delay interval in order to overcome a prepotent response tendency (target responses are required when an X is presented but only in the context of a preceding A; non-target conditions are AY, BX and BY). The dependent measure was d-prime at the long delay (calculated as AX hits minus BX false alarms, which is particularly sensitive to context processing impairments in individuals with schizophrenia.
Preparing to Overcome Prepotency (POP) Task - Reaction Time	Week 4	The POP task is a cued stimulus-response reversal paradigm that, similar to the AX Continuous Performance Test, requires increases in cognitive control through the maintenance and use of context information to overcome prepotent response tendencies.
Preparing to Overcome Prepotency Task - Error Rate	Week 4	The POP task is a cued stimulus-response reversal paradigm that, similar to the AX Continuous Performance Test, requires increases in cognitive control through the maintenance and use of context information to overcome prepotent response tendencies.

Secondary Outcome Measures

Name	Time	Method
Brief Psychiatric Rating Scale Total Score	Week 4	The Brief Psychiatric Rating Scale-anchored (BPRS; Overall and Gorham, 1962; Woerner, Mannuzza, Kane, 1988) is an 18-item scale that is among the most widely used measure of psychopathology. Scores range from 1-7, with higher scores reflecting greater pathology. A total score is derived from the sum of all 18 items (possible scores range from 18-126). It relies on clinical judgment in the assessment of key areas of psychopathology (depression, anxiety, psychosis).
Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Total Score	Week 4	Five index scores are computed from the RBANS (immediate memory, language, visuospatial, attention, delayed memory) that are combined to provide the Total Score. The Total Score is expressed as a standardized score normalized to a population mean of 100, with a standard deviation of 15 (possible scores 40-135). Higher scores reflect better performance. All subjects received the "A" form at baseline and the wk-4 visit and the "B" form at the wk-2 visit (the A/B forms are equivalent alternate forms, which allow for retesting patients without the confound of practice effects).
Repeatable Battery for the Assessment of Neuropsychological Status - Delayed Memory Subindex	Week 4	The Delayed Memory Index consists of verbal and nonverbal recall tasks (words, drawings) that the subject views early in the evaluation and without warning, is asked to recall \~1/2 hr later. Scores are expressed as standardized scores normalized to a population mean of 100, with a standard deviation of 15 (possible scores between 40-135). Higher scores reflect better performance. Subjects received the "A" form at baseline and wk-4 visit and the "B" form at the wk-2 visit (A/B forms are equivalent alternate forms, which allow for retesting patients without the confound of practice effects).