Clinical trial NCT00129441: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Schizophrenia
Keywords: schizophrenia
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2005-08-11
Enrollment: 16
Sex: MALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: N-back Task - Reaction Time
timeFrame: Week 4
measure: N-back Task - Error Rate
timeFrame: Week 4
measure: AX Continuous Performance Test Task D-prime
timeFrame: Week 4
measure: Preparing to Overcome Prepotency (POP) Task - Reaction Time
timeFrame: Week 4
measure: Preparing to Overcome Prepotency Task - Error Rate
timeFrame: Week 4
Secondary outcomes:
measure: Brief Psychiatric Rating Scale Total Score
timeFrame: Week 4
measure: Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Total Score
timeFrame: Week 4
measure: Repeatable Battery for the Assessment of Neuropsychological Status - Delayed Memory Subindex
timeFrame: Week 4
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: David A Lewis, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.