Back to resultsGamma-Amino Butyric Acid (GABA)-A Alpha2/3 Study
Primary Purpose
Schizophrenia
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Merck L-830982
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Schizophrenia focused on measuring schizophrenia
Eligibility 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
Sites / Locations
- University of Pittsburgh
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Merck L-830982
Sugar pill
Arm Description
Outcomes
Primary Outcome Measures
N-back Task - Reaction Time
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
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
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
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
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
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
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
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).
Full Information
NCT ID
NCT00129441
First Posted
August 10, 2005
Last Updated
October 14, 2011
Sponsor
University of Pittsburgh
Collaborators
Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT00129441
Brief Title
Gamma-Amino Butyric Acid (GABA)-A Alpha2/3 Study
Official Title
Treatment of Cognitive Disability in Schizophrenia With a GABA-A Alpha2/3 Receptor Agonist
Study Type
Interventional
2. Study Status
Record Verification Date
October 2011
Overall Recruitment Status
Completed
Study Start Date
August 2005 (undefined)
Primary Completion Date
January 2008 (Actual)
Study Completion Date
January 2008 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Pittsburgh
Collaborators
Merck Sharp & Dohme LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia
Keywords
schizophrenia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
16 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Merck L-830982
Arm Type
Experimental
Arm Title
Sugar pill
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Merck L-830982
Other Intervention Name(s)
MK-0777
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Medications were dispensed weekly in blister packs by the hospital pharmacy, using the same number of pills as those on active drug.
Primary Outcome Measure Information:
Title
N-back Task - Reaction Time
Description
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.
Time Frame
Week 4
Title
N-back Task - Error Rate
Description
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.
Time Frame
Week 4
Title
AX Continuous Performance Test Task D-prime
Description
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.
Time Frame
Week 4
Title
Preparing to Overcome Prepotency (POP) Task - Reaction Time
Description
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.
Time Frame
Week 4
Title
Preparing to Overcome Prepotency Task - Error Rate
Description
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.
Time Frame
Week 4
Secondary Outcome Measure Information:
Title
Brief Psychiatric Rating Scale Total Score
Description
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).
Time Frame
Week 4
Title
Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Total Score
Description
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).
Time Frame
Week 4
Title
Repeatable Battery for the Assessment of Neuropsychological Status - Delayed Memory Subindex
Description
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).
Time Frame
Week 4
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David A Lewis, MD
Organizational Affiliation
University of Pittsburgh
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
15803162
Citation
Lewis DA, Hashimoto T, Volk DW. Cortical inhibitory neurons and schizophrenia. Nat Rev Neurosci. 2005 Apr;6(4):312-24. doi: 10.1038/nrn1648.
Results Reference
background
PubMed Identifier
15205885
Citation
Lewis DA, Volk DW, Hashimoto T. Selective alterations in prefrontal cortical GABA neurotransmission in schizophrenia: a novel target for the treatment of working memory dysfunction. Psychopharmacology (Berl). 2004 Jun;174(1):143-50. doi: 10.1007/s00213-003-1673-x. Epub 2003 Dec 9.
Results Reference
background
PubMed Identifier
18923067
Citation
Lewis DA, Cho RY, Carter CS, Eklund K, Forster S, Kelly MA, Montrose D. Subunit-selective modulation of GABA type A receptor neurotransmission and cognition in schizophrenia. Am J Psychiatry. 2008 Dec;165(12):1585-93. doi: 10.1176/appi.ajp.2008.08030395. Epub 2008 Oct 15. Erratum In: Am J Psychiatry. 2009 Jan;166(1):120.
Results Reference
result
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Gamma-Amino Butyric Acid (GABA)-A Alpha2/3 Study
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