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.

Conditions

• Schizophrenia

Interventions

DRUG

MK-0777

MK-0777 GEM, 8 mg BID

DRUG

MK-0777

MK-0777 GEM, 3 mg BID

DRUG

placebo

2 tablets placebo BID

Sponsors & Collaborators

• University of Maryland

  collaborator OTHER

• Washington University School of Medicine

  collaborator OTHER

• Massachusetts General Hospital

  collaborator OTHER

• Nathan Kline Institute for Psychiatric Research

  collaborator OTHER

• Columbia University

  collaborator OTHER

• Duke University

  collaborator OTHER

• Beth Israel Deaconess Medical Center

  collaborator OTHER

• University of California, Los Angeles

  lead OTHER

Principal Investigators

• Robert W Buchanan, M.D. · Maryland Psychiatric Research Center

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

60 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2007-07-31

Primary Completion

2009-09-30

Completion

2009-09-30

Countries

• United States

Study Locations