A D1 Agonist For Working Memory
Condition: Schizotypal Personality Disorder; SPD
MeSH terms: Personality Disorders; Schizotypal Personality Disorder
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of the study is to examine the effects of the administration of a drug called
      DAR-0100A on attention and memory in persons with schizotypal personality disorder (SPD).
      DAR-0100A has not been FDA approved, however in recent studies has been used to treat
      cognitive deficits, meaning problems in the way you organize your thinking, in people
      diagnosed with schizophrenia.

      Many people who carry a diagnosis of schizotypal personality disorder have trouble with
      attention and memory. Increasing the presence of a brain chemical called dopamine has been
      found to help people with schizophrenia with their attention and memory problems. This study
      will investigate whether the same is true for people with schizotypal personality disorder by
      using DAR-0100A, a drug that has been shown to help with the cognitive deficits of people
      with Parkinson's disease by increasing dopamine effects. Information collected in this
      experiment may lead to a better understanding of the brain mechanisms involved in schizotypal
      personality disorder and improve treatments for the psychological problems associated with
      this condition.
    

Detailed description: 
      Primary Aims:

        1. To perform a 5-year study in which three consecutive days of DAR-0100A at a dose of 15
           mg or placebo are administered intravenously over 30 minutes to 60 patients with SPD
           (12/yr) in a between-groups, randomized, double-blind design. Cognitive testing will be
           performed at baseline (Visit 1) and on the third day of drug/placebo administration
           (Visit 4). Subjects will return a minimum of two weeks later for Visit 5 to receive drug
           (if randomized initially to placebo) or placebo (if randomized to drug) in a double
           blind fashion in an identical protocol. This allows all patients to receive drug for
           Secondary Aim 1 while maintaining the blind. Baseline (Visit 1) and repeat cognitive
           testing (Visit 4) is also administered to 60 healthy controls per year (12/yr). The
           cognitive tests of working memory serving as primary outcome measures will include the
           modified AX-CPT (accuracy scores for AX, AY and BX and ANOVA), the N-back (delta
           difference 0-back-2-back), and the Paced Auditory Serial Addition Task (PASAT) (%
           correct and ANOVA). Other tests included are tests of working and verbal memory,
           executive function, and verbal learning for secondary outcome measures as well as
           comparison tests not hypothesized to change with drug.

        2. To compare changes on the primary outcome measures from baseline to Visit 4 testing
           between drug and placebo administration in SPD subjects.

        3. To compare primary outcome variables from baseline to Visit 4 between patients groups
           and healthy controls.

        4. To obtain plasma DAR-0100A concentrations on Visit 4 to evaluate plasma concentrations
           in relation to cognitive changes as a potential covariate.

      Secondary Aims:

        1. To evaluate the change between baseline and Visit 4 cognitive testing in all SPD
           patients receiving drug in the first or second phase.

        2. To evaluate secondary outcome and comparison variables between SPD patients on placebo
           and drug.

      Primary Hypotheses:

      1. Baseline primary outcome measures will be impaired in SPD subjects compared to controls.
      2. SPD subjects on DAR-0100A will show improvement on primary measures greater than healthy
      controls and SPD patients randomized to placebo between baseline and Visit 4.

      3. SPD patients will show significant improvements on primary outcome variables on drug
      compared to placebo but not on comparis-on perceptual (JLOT) and processing speed/attentional
      tasks (Trails A).
    

Intervention name(s): DAR 0-100A; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 15 mg DAR 0100A is dissolved in 150 cc NS administered over 30 minutes intravenously.; 15 mg DAR placebo is dissolved in 150 cc NS administered over 30 minutes intravenously.
Other intervention name(s): DHX; dihydrexidine
Intervention MeSH terms: Dihydrexidine
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Care Provider)
Primary purpose: Treatment
Keywords: schizotypal personality disorder; cognitive impairment; working memory; Dopamine Agonists; Cognition Disorders; Personality Disorders; Delirium; Dementia; Amnestic; Cognitive Disorders; Mental Disorders; Dihydrexidine; Dopamine A