Treatment Study for Cognitive Deficits in Schizophrenia (TURNS)

This study has been completed.
Sponsor:
Collaborators:
University of Maryland
Washington University School of Medicine
Massachusetts General Hospital
Nathan Kline Institute for Psychiatric Research
Columbia University
Duke University
Beth Israel Deaconess Medical Center
Information provided by (Responsible Party):
Stephen R. Marder, University of California, Los Angeles
ClinicalTrials.gov Identifier:
NCT00505076
First received: July 19, 2007
Last updated: October 30, 2014
Last verified: October 2014
  Purpose

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.


Condition Intervention Phase
Schizophrenia
Drug: MK-0777
Drug: placebo
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by University of California, Los Angeles:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 63
Study Start Date: July 2007
Study Completion Date: September 2009
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MK-0777 8 mg
MK-0777 8 mg tablet by mouth twice daily for 4 weeks
Drug: MK-0777
MK-0777 GEM, 8 mg BID
Experimental: MK-0777 3 mg
MK-0777 3 mg tablet by mouth twice daily for 4 weeks
Drug: MK-0777
MK-0777 GEM, 3 mg BID
Placebo Comparator: Placebo
Placebo tablet by mouth twice daily for 4 weeks
Drug: placebo
2 tablets placebo BID

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis: DSM IV/DSM IV TR schizophrenia (including disorganized, paranoid, undifferentiated, and catatonic subtypes)
  • Capable of providing informed consent
  • Duration of illness equal to or greater than one year
  • Treated with one or two of the following second generation antipsychotics: risperidone, paliperidone, olanzapine, quetiapine, ziprasidone, or aripiprazole for the previous two months, with no change in dose in the last month.
  • Meet the following symptom criteria:

    • Brief Psychiatric Rating Scale (BPRS) Hallucinatory Behavior, Unusual Thought Content or Conceptual Disorganization item score ≤ 4
    • All Scale for the Assessment of Negative Symptoms global items ≤ 3
    • Simpson-Angus Scale total score ≤ 6
    • Calgary Depression Scale total score ≤ 10
  • Meet the following cognitive performance criteria:

    • Performance less than the maximum cutoff (in parentheses) for ONE of the following MCCB tests: i.) Letter-number span (20); ii.) HVLT total (31); and iii.) CPT d-prime (3.47)
    • Able to complete the baseline MCCB validly
    • Raw score ≥6 on the WTAR

Exclusion Criteria:

  • Current treatment (within 4 weeks) with conventional antipsychotics (e.g. fluphenazine, haloperidol) or clozapine
  • Current treatment with psychotropic agents known to act at the GABAA receptor, including benzodiazepines; sedative-hypnotics other than trazadone and chloral hydrate; carbamazepine, gabapentin, lamotrigine, and valproic acid
  • Current treatment with a drug that inhibits CYP3A4, including: cimetidine; cyclosporine; erythromycin or erythromycin-like drugs (e.g., azithromycin, clarithromycin); diltiazem; fluoxetine, fluovoxamine; itraconazole, ketoconazole or other systemic antifungal agents in the azole class; nefazodone; or induce CYP3A4, including: carbamazepine, modafinil; phenobarbital; phenytoin; rifampin; St. Johns wort; and troglitazone.
  • Current treatment with psychotropic agents known to effect cognition: amphetamine; barbiturates; lithium; MAOIs; methylphenidate
  • Current treatment with herbal preparations with possible psychotropic effects (e.g., St. Johns wort, kava-kava, Valerian, S-Adenosyl Methionine [SAMe])
  • Current treatment with systemic steroids
  • DSM-IV diagnosis of alcohol or substance abuse (other than nicotine) within the last month or a DSM-IV diagnosis of alcohol or substance dependence within the last 6 months
  • Presence of PI or greater posterior subcapsular cataracts
  • Uveitis with 1+ or greater flare or cells
  • Nuclear or cortical cataracts
  • History of significant head injury/trauma, as defined by one or more of the following: loss of consciousness (LOC) for more than 1 hour, seizures from the head injury, clear cognitive sequellae of the injury, or cognitive rehabilitation following the injury
  • History of clinically significant neurological, metabolic, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, and/or urological disorders.
  • Clinically significant abnormalities in physical examination, ECG, or laboratory assessments
  • A positive test for Hepatitis C antibody with concurrent evidence of impaired hepatic function (increased AST or ALT greater than 2 times the upper limit of normal) or positive tests for Hepatitis A antibody IgM fraction or Hepatitis B surface antigen, irrespective of the AST or ALT values.
  • Pregnant women or women of child-bearing potential, either not surgically-sterile or using appropriate methods of birth control
  • Women who are breast-feeding
  • History of severe symptoms of benzodiazepine withdrawal (e.g., history of seizures or delirium associated with withdrawal)
  • Received ECT treatment within the last 3 months
  • Participated in a clinical trial of any other psychotropic medication within 2 months
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00505076

Locations
United States, California
UCLA
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
Sponsors and Collaborators
University of California, Los Angeles
University of Maryland
Washington University School of Medicine
Massachusetts General Hospital
Nathan Kline Institute for Psychiatric Research
Columbia University
Duke University
Beth Israel Deaconess Medical Center
Investigators
Principal Investigator: Robert W Buchanan, M.D. University of Maryland
  More Information

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Stephen R. Marder, Principal Investigator, University of California, Los Angeles
ClinicalTrials.gov Identifier: NCT00505076     History of Changes
Other Study ID Numbers: TURNS02, HHSN278200441003C
Study First Received: July 19, 2007
Results First Received: April 27, 2011
Last Updated: October 30, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of California, Los Angeles:
Cognition
Schizophrenia

Additional relevant MeSH terms:
Schizophrenia
Mental Disorders
Schizophrenia and Disorders with Psychotic Features

ClinicalTrials.gov processed this record on July 30, 2015