A Multicenter Study of NAP (AL-108) in Schizophrenia
Condition: Schizophrenia
MeSH terms: Schizophrenia
Intervention: AL-108; AL-108; Placebo; Placebo
Intervention description: AL-108, 5 mg/day- one spray in each nostril once per day; AL-108, 30 mg/day- 3 sprays in each nostril, twice per day; Placebo- 3 sprays in each nostril, twice per day; Placebo- one spray in each nostril, once per day
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 63.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No
Keywords: Cognition; Schizophrenia

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.
    

Eligibility 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.