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Org 24448 (Ampakine) for Cognitive Deficits in Schizophrenia

This study has been terminated.
( Study terminated at Sponsor's request. )

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
Information provided by: University of California, Los Angeles
ClinicalTrials.gov Identifier: NCT00425815
  Purpose

The TURNS is a NIMH-funded contract for the evaluation of new compounds for the treatment of cognitive impairments in schizophrenia (HHSN 27820044 1003C; P.I.: Steve Marder, M.D.). Despite advances in the safety, tolerability, and effectiveness of antipsychotic medications for the treatment of schizophrenia, many patients continue to be plagued by impairments in social and work functioning. Persons with schizophrenia commonly show deficits in a number of areas of cognition that include impairments in attention, memory, and executive functioning (the ability and organize one’s behavior). Importantly, a large body of literature now shows a link between cognition and community functioning in schizophrenia. It is believed that treatments that improve cognitive deficits may lead to improvements in work and social functioning.

A promising approach to improve the community functioning of patients with schizophrenia is to develop new agents that treat the cognitive deficits of the illness. One type of pharmacological compound that has shown promise at improving cognition is a group of drugs called ampakines. These drugs are believed to improve the activity of a neurotransmitter system in the brain called the glutamate system. Increased activity of this system has been linked to improvements in cognitive functioning. The current study is an eight-week trial comparing two doses of the ampakine drug, Org 24448, that will be added to patients’ current atypical antipsychotic medication. One hundred thirty-five patients with schizophrenia, drawn from seven sites, will participate in the study. Cognition will be measured using a variety of paper-and-pencil and computerized measures from the consensus-derived NIMH-MATRICS cognitive battery. Psychiatric symptoms and the ability to perform community-based tasks of daily living will also be measured. Because previous trials with this drug and other similar drugs have detected lasting cognitive benefits, this trial will also repeat clinical assessments four weeks after completion of the study medication.


Condition Intervention Phase
Schizophrenia
Drug: Org 24448 (Ampakine)
Phase II

MedlinePlus related topics:   Schizophrenia   

U.S. FDA Resources

Study Type:   Interventional
Study Design:   Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:   A Placebo-Controlled Trial of Org 24448 (Ampakine) Added to Atypical Antipsychotics in Patients With Schizophrenia

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

Primary Outcome Measures:
  • MCCB: MATRICS Consensus Cognitive Battery

Secondary Outcome Measures:
  • UPSA: UCSD Performance-Based Skills Assessment
  • SCoRS: Schizophrenia Cognition Rating Scale

Estimated Enrollment:   135

Show detailed description  Show Detailed Description

  Eligibility
Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Criteria

Inclusion Criteria:

  1. Diagnosis: schizophrenia, any subtype (DSM-IV/DSM-IV-TR)
  2. Age: 18-55 years
  3. Gender: male or female
  4. Capable of providing informed consent
  5. Antipsychotic: aripiprazole, olanzapine, quetiapine, risperidone or ziprasidone.
  6. Subjects must have been maintained on current psychotropic medications for 8 weeks and on current doses for 4 weeks.
  7. Subjects must be clinically stable and in the residual (non-acute) phase of their illness for at least 12 weeks.
  8. Symptom Ratings:

    • No more than a “moderate” severity rating on hallucinations and delusions (i.e., Brief Psychiatric Rating Scale (BPRS) Hallucinatory Behavior or Unusual Thought Content item score  4)
    • No more than a “moderate” severity rating on positive formal thought disorder (i.e., BPRS Conceptual Disorganization item score  4)
    • No more than “moderate” severity rating on negative symptoms (i.e., all Scale for the Assessment of Negative Symptoms global items  3)
    • A minimal level of extrapyramidal symptoms (i.e., Simpson-Angus Scale total score  6)
    • A minimal level of depressive symptoms (i.e., Calgary Depression Scale total score  10).
  9. Cognitive Status:

    • Performance less than the maximum cutoff (in parentheses) for ONE of the following MCCB tests:

      • Letter-number span (20);
      • HVLT total (31); and
      • CPT d-prime (3.47)
    • Able to complete the baseline MCCB validly as assessed by Chief Neuropsychologist or NP tester
    • Raw score of 6 or greater on the WTAR

Exclusion Criteria:

  1. Concomitant medications are allowed except for:

    • Conventional antipsychotics and clozapine
    • Antipsychotic polypharmacy
    • Anticholinergic agents (including anticholinergic antidepressants)
    • Carbamazepine, phenytoin and lamotrigine
  2. DSM-IV/DSM-IV-TR diagnosis of alcohol or substance abuse (other than nicotine) within the last 3 months or a DSM-IV/DSM-IV-TR diagnosis of alcohol or substance dependence (other than nicotine) within the last 6 months
  3. A history of significant head injury/trauma, as defined by:

    • Loss of consciousness (LOC) for more than 1 hour
    • Recurring seizures resulting from the head injury
    • Clear cognitive sequellae of the injury
    • Cognitive rehabilitation following the injury
  4. History of seizures or abnormal EEG
  5. Epileptogenic abnormalities on screening EEG
  6. A baseline white blood count (WBC) less than 3500/mm3 or absolute neutrophil count (ANC) less than 2000/mm3
  7. Serious medical or neurological illness (unstable cardiac disease, AIDS, malignancy, liver or renal impairment) or treatment for a medical disorder that could interfere with study participation.
  8. History of transient ischemic attack (TIA) or cerebral vascular accident (CVA)
  9. History of neutropenia or medication-induced blood dyscrasia
  10. Clinically-significant abnormalities on screening laboratory or EKG.
  11. Untreated hyper- or hypothyroidism
  12. Pregnancy, nursing, or if female and fertile, unwilling to use appropriate birth control measures during study participation
  13. Unable to complete neuropsychological tests
  14. Serious suicidal or homicidal risk within the past six months
  15. Participation in a trial of another investigational agent within 2 months
  16. Treatment with ECT within 2 months
  Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00425815

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
Massachusetts General Hospital    
      Boston, Massachusetts, United States, 02114
Harvard Medical School    
      Boston, Massachusetts, United States, 02215
United States, Missouri
Washington University School of Medicine    
      St. Louis, Missouri, United States, 63110
United States, New York
Nathan Kline Institute    
      Orangeburg, New York, United States, 10962
Columbia University Medical Center    
      New York, New York, United States, 10032
United States, North Carolina
Duke University Medical Center    
      Durham, North Carolina, United States, 27710

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:     Don C Goff, MD     Harvard University    
  More Information


Study ID Numbers:   TURNS01
First Received:   January 22, 2007
Last Updated:   July 18, 2007
ClinicalTrials.gov Identifier:   NCT00425815
Health Authority:   United States: Food and Drug Administration

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

Study placed in the following topic categories:
Schizophrenia
Mental Disorders
Psychotic Disorders
Schizophrenia and Disorders with Psychotic Features

ClinicalTrials.gov processed this record on October 03, 2008




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