Treatment Study for Cognitive Deficits in Schizophrenia
Summary
Patients with schizophrenia are characterized by a broad range of neurocognitive abnormalities. These include impairments in attention, including abnormalities in sensory gating; executive function; visual and verbal learning and memory; working memory; processing speed; and social cognition (Nuechterlein et al, 2004). These impairments are major determinants of poor functional outcome in patients with schizophrenia (Green, 1996; Green et al, 2004). Conventional antipsychotics have limited effects on these impairments. Second generation antipsychotics may have modest benefits for cognitive function, but whether this represents a direct cognitive enhancing effect has not been established. Regardless, patients continue to exhibit pronounced cognitive impairments despite adequate second generation antipsychotic treatment. Adjunctive pharmacotherapy may offer a viable approach for the treatment of cognitive impairments. Adjunctive agents can be used to modulate specific neurotransmitter systems that are hypothesized to be involved in the pharmacology of cognitive functions. The standard of care for schizophrenia is antipsychotic medications to treat psychotic symptoms. However, cognitive impairments remain and these impairments have been found to be significantly associated with the poor psychosocial function observed in patients with schizophrenia. There is a considerable preclinical rationale for the use of drugs that act at the Gamma-amino-buyric acid (GABA) α2 subunit as adjunctive treatments to target cognitive impairments. MK-0777 GEM (Merck-0777 Gel Extrusion Module) formulation provides an opportunity to directly test this mechanism. The purpose of the proposed study is to examine the efficacy and safety of two doses of MK (Merck) -0777 GEM, 3 mg BID (twice daily) and 8 mg BID (twice daily), in the treatment of cognitive impairments in patients with schizophrenia. Secondary goals are to determine whether MK-0777 has beneficial effects on measures of functional capacity and patient self-report of cognitive function.
Timeline
- Start
- 2007-07
- Primary completion
- 2009-09
- Completion
- 2009-09
Outcome
Missed primary endpoint
registry analysis (superiority or other test); MK-077 8 mg BID vs MK-0777 3 mg BID vs Placebo BID; p = 0.21; ANCOVA NCT00505076 ↗
paper There were no significant group differences on the primary outcome measure, the MATRICS Consensus Cognitive Battery composite score. PMID 21145041 ↗
Publications
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Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | MK0777 | Small molecule | 3 mg | Oral |
| Subject | MK0777 | Small molecule | 8 mg | Oral |