A D1 Agonist For Working Memory

Study Overview
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Brief Summary
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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
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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: 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).

Official Title
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A D1 Agonist For Working Memory Enhancement In The Schizophrenia Spectrum

Conditions
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Schizotypal Personality Disorder, SPD

Intervention / Treatment
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* Drug: DAR 0-100A
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DAR 0-100A then Placebo<br>15 mg is dissolved in 150 cc NS administered over 30 minutes x 3 consecutive days. 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). | Drug: DAR 0-100A<br>* 15 mg DAR 0100A is dissolved in 150 cc NS administered over 30 minutes intravenously.<br>* Other names: dihydrexidine;Drug: Placebo<br>* 15 mg DAR placebo is dissolved in 150 cc NS administered over 30 minutes intravenously.<br>|
| Placebo Comparator: Placebo then DAR 0-100A<br>15 mg dissolved in 150 cc NS saline is administered over 30 minutes x 3 consecutive days. 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). | Drug: DAR 0-100A<br>* 15 mg DAR 0100A is dissolved in 150 cc NS administered over 30 minutes intravenously.<br>* Other names: dihydrexidine;Drug: Placebo<br>* 15 mg DAR placebo is dissolved in 150 cc NS administered over 30 minutes intravenously.<br>|
| No Intervention: Healthy Control<br>patients without diagnosis of SPD | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Modified AX-CPT (d') | A cognitive test of working memory | Baseline performance | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Modified AX-CPT (d') | A cognitive test of working memory | Day one | 
| The Modified AX-CPT (d') | A cognitive test of working memory | Day three | 
| The Modified AX-CPT (d') | A cognitive test of working memory | One month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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schizotypal personality disorder, cognitive impairment, working memory, Dopamine Agonists, Cognition Disorders, Personality Disorders, Delirium, Dementia, Amnestic, Cognitive Disorders, Mental Disorders, Dihydrexidine, Dopamine A