A Multicenter Study of NAP (AL-108) in Schizophrenia

• Status: Completed
• Trial end date: 2009-04-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

One approach to improve the community functioning of patients with schizophrenia is to develop new agents that treat the cognitive deficits of the illness. A promising agent is called AL-108. This drug is administered as a nasal spray. Studies in animals suggest that this drug may protect neurons and may improve cognition in schizophrenia. The current study is a twelve-week multicenter, double-blind, randomized clinical trial of two doses of AL-108 (5 and 30 mg/day intranasally) versus placebo in the treatment of persistent cognitive dysfunction in schizophrenia. The study medication will be added to patients' current atypical antipsychotic medication or to their current injectable first-generation antipsychotic medication. The primary outcome measure will consist of the composite score of the MATRICS neuropsychological battery. Secondary outcome measures will include scores on symptoms, functional outcome, and safety measures. Sixty clinically stable patients with schizophrenia, drawn from eight sites, will participate in the study. Twenty-five patients will be enrolled at UCLA.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of California, Los Angeles
• Collaborators: Beth Israel Deaconess Medical Center; Columbia University; Duke University; Massachusetts General Hospital; Nathan Kline Institute for Psychiatric Research; University of Maryland; University of Maryland, College Park; Washington University School of Medicine

Criteria

Inclusion Criteria:

• DSM IV/DSM IV TR diagnosis of schizophrenia

• Capable of providing informed consent

• Males and Females

• Age: 18 and 60

• Caucasian or Non Caucasian

• Subjects will be treated with one of the following second generation antipsychotics:

risperidone, olanzapine, quetiapine, ziprasidone, or aripiprazole for the previous two months, with no change in dose in the last month, and/or with injectable depot antipsychotics (fluphenazine or haloperidol decanoate) with no change in last 3 months.

• Subjects will meet the following symptom criteria:

• Average Brief Psychiatric Rating Scale (BPRS) item score >3 (mild)

• Simpson-Angus Scale total score less than or equal to 6

• Calgary Depression Scale total score less than or equal to 10

• Subjects will meet the following cognitive performance criteria:

• 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:

• Current treatment with oral conventional antipsychotics (e.g. fluphenazine, haloperidol) or clozapine.

• Subjects with a 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 (other than nicotine) within the last 6 months

• Subjects with a history of significant head injury/trauma, as defined by one or more of the following:

• 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

• Subjects with a clinically significant neurological, metabolic, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, and/or urological disorder (e.g. unstable angina, decompensated congestive heart failure, CNS infection or history of HIV seropositivity), which would pose a risk to the patient if they were to participate in the study or that might confound the results of the study.

• Clinically significant abnormalities in physical examination, ECG, or laboratory assessments.

• Clinically significant renal disease.

• Women who are pregnant or of child-bearing potential, either not surgically-sterile nor using appropriate methods of birth control

• Women who are breast-feeding

• Prior participation in a clinical trial of investigational medication within 60 days.