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

This study has been completed.
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT00129441
First received: August 10, 2005
Last updated: October 14, 2011
Last verified: October 2011
  Purpose

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.


Condition Intervention Phase
Schizophrenia
Drug: Merck L-830982
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Treatment of Cognitive Disability in Schizophrenia With a GABA-A Alpha2/3 Receptor Agonist

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • N-back Task - Reaction Time [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
    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:
  • Brief Psychiatric Rating Scale Total Score [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
    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).


Enrollment: 16
Study Start Date: August 2005
Study Completion Date: January 2008
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Merck L-830982 Drug: Merck L-830982
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 Name: MK-0777
Placebo Comparator: Sugar pill Drug: Placebo
Medications were dispensed weekly in blister packs by the hospital pharmacy, using the same number of pills as those on active drug.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00129441

Locations
United States, Pennsylvania
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
Sponsors and Collaborators
University of Pittsburgh
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: David A Lewis, MD University of Pittsburgh
  More Information

Publications:
Responsible Party: University of Pittsburgh
ClinicalTrials.gov Identifier: NCT00129441     History of Changes
Other Study ID Numbers: 0502027
Study First Received: August 10, 2005
Results First Received: May 25, 2011
Last Updated: October 14, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Pittsburgh:
schizophrenia

Additional relevant MeSH terms:
Schizophrenia
Mental Disorders
Schizophrenia and Disorders with Psychotic Features
Gamma-Aminobutyric Acid
GABA Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 23, 2014