Org 24448 (Ampakine) for Cognitive Deficits in Schizophrenia

NCT00425815 | Withdrawn Phase 2

• 1 other identifier: TURNS01
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 8

Brief Summary

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.

Conditions

Schizophrenia

Keywords

Cognition; Ampakines; Schizophrenia

Outcome Measures

Primary Outcomes (1)

• MCCB: MATRICS Consensus Cognitive Battery

  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.

  Baseline, Week 4 and Week 8

Secondary Outcomes (2)

• UPSA: UCSD Performance-Based Skills Assessment

  Baseline, Week 4 and Week 8

• SCoRS: Schizophrenia Cognition Rating Scale

  Baseline, Week 4 and Week 8

Study Arms (3)

Org 24448 250 mg

EXPERIMENTAL

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

Og 244448 500 mg

EXPERIMENTAL

Two capsules (two Org 24448 250 mg capsules) will be ingested orally daily for eight weeks.

Drug: Org 24448

Inactive Capsule

PLACEBO COMPARATOR

Two capsules (two placebo capsules that are identical to the active treatment) will be ingested orally daily for eight weeks.

Other: Placebo

Interventions

Org 24448 DRUG

Org 24448 is a moderate-potency selective AMPA positive modulator that enhances the glutamate system in the brain.

Also known as: Ampakine

Og 244448 500 mg; Org 24448 250 mg

Placebo OTHER

Placebo comparison

Inactive Capsule

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Diagnosis: schizophrenia, any subtype (DSM-IV/DSM-IV-TR)
• Age: 18-55 years
• Gender: male or female
• Capable of providing informed consent
• Antipsychotic: aripiprazole, olanzapine, quetiapine, risperidone or ziprasidone.
• Subjects must have been maintained on current psychotropic medications for 8 weeks and on current doses for 4 weeks.
• Subjects must be clinically stable and in the residual (non-acute) phase of their illness for at least 12 weeks.
• 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).
• Cognitive Status:
• Performance less than the maximum cutoff (in parentheses) for ONE of the following MCCB tests:

You may not qualify if:

• Concomitant medications are allowed except for:
• Conventional antipsychotics and clozapine
• Antipsychotic polypharmacy
• Anticholinergic agents (including anticholinergic antidepressants)
• Carbamazepine, phenytoin and lamotrigine
• 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
• 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
• History of seizures or abnormal EEG
• Epileptogenic abnormalities on screening EEG
• A baseline white blood count (WBC) less than 3500/mm3 or absolute neutrophil count (ANC) less than 2000/mm3
• 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.

Sponsors & Collaborators

• University of California, Los Angeles: lead
• University of Maryland: collaborator
• Washington University School of Medicine: collaborator
• Massachusetts General Hospital: collaborator
• Nathan Kline Institute for Psychiatric Research: collaborator
• Columbia University: collaborator
• Duke University: collaborator
• Beth Israel Deaconess Medical Center: collaborator

Study Sites (8)

UCLA

Los Angeles, California, 90073, United States

Location

Maryland Psychiatric Research Center

Catonsville, Maryland, 21228, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Harvard Medical School

Boston, Massachusetts, 02215, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Nathan Kline Institute

Orangeburg, New York, 10962, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Schizophrenia

Interventions

1-(benzofurazan-5-ylcarbonyl)piperidine

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Study Officials

• Don C Goff, MD

  Harvard University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 22, 2007
• First Posted: January 23, 2007
• Study Start: April 1, 2009
• Primary Completion: April 1, 2009
• Study Completion: April 1, 2009
• Last Updated: February 9, 2016

Record last verified: 2016-02

Locations

US (8)