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Completed

NCT Number: NCT00129441

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

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.

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Key information

Age range

18 year–50 year

Sex eligibility

Male

Study type

Interventional

Phase

Phase 2

Primary location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Merck L-830982

Drug

The initial dose of L-830982 was 3.0 mg twice daily (b.i.d.) the dosage increased to 5.0 mg b.i.d. at the end of week 1 and 8.0 mg b.i.d. at the end of week 2, which was continued for the remaining 2 weeks of the trial. Medications were dispensed weekly in blister packs by the hospital pharmacy.

Other names: MK-0777

Placebo

Drug

Medications were dispensed weekly in blister packs by the hospital pharmacy, using the same number of pills as those on active drug.

Primary outcomes

  1. N-back Task - Reaction Time

    Time frame: 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.

  2. N-back Task - Error Rate

    Time frame: 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.

  3. AX Continuous Performance Test Task D-prime

    Time frame: 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.

  4. Preparing to Overcome Prepotency (POP) Task - Reaction Time

    Time frame: 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.

  5. Preparing to Overcome Prepotency Task - Error Rate

    Time frame: 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 outcomes

  1. Brief Psychiatric Rating Scale Total Score

    Time frame: 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).

  2. Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Total Score

    Time frame: 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).

  3. Repeatable Battery for the Assessment of Neuropsychological Status - Delayed Memory Subindex

    Time frame: 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).

Sponsors and collaborators

Lead sponsor

University of Pittsburgh

Other

Collaborators

  • Merck Sharp & Dohme LLC

Registry information

Official study title

Treatment of Cognitive Disability in Schizophrenia With a GABA-A Alpha2/3 Receptor Agonist

Important dates

Study start
2005
Primary completion
2008
Study completion
2008
First posted
Aug 11, 2005
Registry last updated
Oct 17, 2011

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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