A D1 Agonist For Working Memory

Primary Aims:

• 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.
• To compare changes on the primary outcome measures from baseline to Visit 4 testing between drug and placebo administration in SPD subjects.
• To compare primary outcome variables from baseline to Visit 4 between patients groups and healthy controls.
• To obtain plasma DAR-0100A concentrations on Visit 4 to evaluate plasma concentrations in relation to cognitive changes as a potential covariate.

Secondary Aims:

• To evaluate the change between baseline and Visit 4 cognitive testing in all SPD patients receiving drug in the first or second phase.
• To evaluate secondary outcome and comparison variables between SPD patients on placebo and drug.

Primary Hypotheses:

• 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.

• 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).

Inclusion criteria

• Currently meeting DSM-IV-TR criteria for Schizotypal
• Personality Disorder
• Males and Females 18 ≤ age ≤ 65
• Medically and neurologically healthy
• Willing and having capacity to provide informed consent

Exclusion criteria

• Currently bipolar I disorder, schizophrenia or current psychosis
• Clinically significant cardiovascular or neurological conditions, uncontrolled hypertension, clinically significant EKG abnormalities, or serious general medical illness
• Clinical evidence of dehydration or significant hypotension
• Currently meeting DSM-IV-TR criteria for Major Depressive Disorder
• Current substance abuse or past dependence within the last six months (other than nicotine)
• Currently taking psychotropic medications
• Currently pregnant or lactating
• Non-English speaking
• Socio-economically disadvantaged people will be included in our research study.