Trial record 1 of 1 for:    NCT00425815
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Org 24448 (Ampakine) for Cognitive Deficits in Schizophrenia

This study has been withdrawn prior to enrollment.
(Study terminated at Sponsor's request.)
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:
NCT00425815
First received: January 22, 2007
Last updated: March 27, 2013
Last verified: March 2013
  Purpose

The TURNS is a National Institute of Mental Health (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 Measurement and Treatment Research to Improve Cognition in Schizophrenia (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
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Placebo-Controlled Trial of Org 24448 (Ampakine) Added to Atypical Antipsychotics in Patients With Schizophrenia

Resource links provided by NLM:


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

Primary Outcome Measures:
  • MCCB: MATRICS Consensus Cognitive Battery [ Time Frame: Baseline, Week 4 and Week 8 ] [ Designated as safety issue: No ]
    The MATRICS Consensus Cognitive Battery assesses cognitive function in the following domains: speed of processing, attention/vigilance, verbal learning, visual learning, reasoning and problem solving, and social cognition.


Secondary Outcome Measures:
  • UPSA: UCSD Performance-Based Skills Assessment [ Time Frame: Baseline, Week 4 and Week 8 ] [ Designated as safety issue: No ]
    The UPSA assesses skills necessary for functioning in the community by asking patients to perform relevant tasks, rating their performance in five areas: household chores, communication, finance, transportation, and planning recreational activities.

  • SCoRS: Schizophrenia Cognition Rating Scale [ Time Frame: Baseline, Week 4 and Week 8 ] [ Designated as safety issue: No ]
    The SCoRS is an assessment of cognitive deficits and the degree to which they affect day-to-day functioning. The items assess the cognitive domains of attention, memory, reasoning and problem solving, working memory, processing speed, language functions, and social cognition.


Enrollment: 0
Study Start Date: April 2009
Study Completion Date: April 2009
Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Org 24448 250 mg
Two capsules (one Org 24448 250 mg capsule and one placebo capsule that is identical to the active treatment) will be ingested orally daily for eight weeks.
Drug: Org 24448
Org 24448 is a moderate-potency selective AMPA positive modulator that enhances the glutamate system in the brain.
Other Name: Ampakine
Experimental: Og 244448 500 mg
Two capsules (two Org 24448 250 mg capsules) will be ingested orally daily for eight weeks.
Drug: Org 24448
Org 24448 is a moderate-potency selective AMPA positive modulator that enhances the glutamate system in the brain.
Other Name: Ampakine
Placebo Comparator: Inactive Capsule
Two capsules (two placebo capsules that are identical to the active treatment) will be ingested orally daily for eight weeks.

  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)
    • Hopkins Verbal Learning Test (HVLT) total (.31) and
    • Continuous Performance Test- Identical Pairs (CPT) d-prime (.3.47)
    • Able to complete the baseline MCCB validly as assessed by Chief Neuropsychologist or neuropsychology 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 sequelae 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 Electroconvulsive therapy (ECT) 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: 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
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, 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

No publications provided

Responsible Party: Stephen R. Marder, Principal Investigator, University of California, Los Angeles
ClinicalTrials.gov Identifier: NCT00425815     History of Changes
Other Study ID Numbers: TURNS01
Study First Received: January 22, 2007
Last Updated: March 27, 2013
Health Authority: United States: Food and Drug Administration

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

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

ClinicalTrials.gov processed this record on September 22, 2014