Treatment Study for Cognitive Deficits in Schizophrenia (TURNS)
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||MK-0777 for the Treatment of Cognitive Impairments in Patients With Schizophrenia|
- Composite MATRICS Consensus Cognitive Battery Score [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]The primary outcome measure is the composite score on the Matrics Consensus Cognitive Battery (MCCB). The MCCB composite score is a standardized mean of the seven domain scores. T-scores are standardized to normative data, and have an estimated mean of 50 and SD of 10 in the general healthy population. Data reduction for analysis of neurocognitive testing used the following steps: i) individual neurocognitive test scores at baseline and follow-up were converted to t-scores; ii) t-scores within the pre-specified cognitive domains measured by more than one test were averaged to obtain a domain-specific t-score; and iii) domain-specific t-scores were averaged to create the MCCB composite score.
- UPSA(UCSD Performance-Based Skills Assessment) Summary Score [ Time Frame: Baseline and end of treatment, a total of four weeks. ] [ Designated as safety issue: No ]The UCSD Performance-Based Skills Assessment assessed functional capacity. The UPSA Summary Score has a range from 0 to 120. A higher score indicates less impairment.
- Schizophrenia Cognition Rating Scale (SCoRS) Score [ Time Frame: 4 Weeks (Baseline to End of Treatment) ] [ Designated as safety issue: No ]The Schizophrenia Cognition Rating Scale (SCoRS) assessed functional capacity. The SCoRS Interviewer Global Rating of function has a range 1 to 10. Higher ratings indicate greater impairment.
|Study Start Date:||July 2007|
|Study Completion Date:||September 2009|
|Primary Completion Date:||September 2009 (Final data collection date for primary outcome measure)|
Experimental: MK-0777 8 mg
MK-0777 8 mg tablet by mouth twice daily for 4 weeks
MK-0777 GEM, 8 mg BID
Experimental: MK-0777 3 mg
MK-0777 3 mg tablet by mouth twice daily for 4 weeks
MK-0777 GEM, 3 mg BID
Placebo Comparator: Placebo
Placebo tablet by mouth twice daily for 4 weeks
2 tablets placebo BID
Show Detailed Description
Please refer to this study by its ClinicalTrials.gov identifier: NCT00505076
|United States, California|
|Los Angeles, California, United States, 90073|
|United States, Maryland|
|Maryland Psychiatric Research Center|
|Catonsville, Maryland, United States, 21228|
|United States, Massachusetts|
|Harvard Medical School|
|Boston, Massachusetts, United States, 02115|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02114|
|United States, Missouri|
|Washington University School of Medicine|
|St. Louis, Missouri, United States, 63110|
|United States, New York|
|Columbia University Medical Center|
|New York, New York, United States, 10032|
|Nathan Kline Institute|
|Orangeburg, New York, United States, 10962|
|United States, North Carolina|
|Duke University Medical Center|
|Durham, North Carolina, United States, 27509|
|Principal Investigator:||Robert W Buchanan, M.D.||University of Maryland|