Clinical trial NCT02507206: A D1 Agonist For Working Memory
Official title: A D1 Agonist For Working Memory Enhancement In The Schizophrenia Spectrum
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Schizotypal Personality Disorder
SPD
Keywords: schizotypal personality disorder
cognitive impairment
working memory
Dopamine Agonists
Cognition Disorders
Personality Disorders
Delirium
Dementia
Amnestic
Cognitive Disorders
Mental Disorders
Dihydrexidine
Dopamine A
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
Collaborators: name: New York State Psychiatric Institute
name: National Institute of Mental Health (NIMH)
First posted: 2015-07-23
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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).

Eligibility criteria: 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.

Primary outcomes:
measure: The Modified AX-CPT (d')
timeFrame: Baseline performance
Secondary outcomes:
measure: The Modified AX-CPT (d')
timeFrame: Day one
measure: The Modified AX-CPT (d')
timeFrame: Day three
measure: The Modified AX-CPT (d')
timeFrame: One month
Other outcomes:
measure: the N-Back
timeFrame: Baseline
measure: the N-Back
timeFrame: Day one
measure: the N-Back
timeFrame: Day three
measure: the N-Back
timeFrame: One month
measure: the DOT Task
timeFrame: Baseline
measure: the DOT Task
timeFrame: Day one
measure: the DOT Task
timeFrame: Day three
measure: the DOT Task
timeFrame: One month
measure: the Paced Auditory Serial Addition Task (PASAT)
timeFrame: Baseline
measure: the Paced Auditory Serial Addition Task (PASAT)
timeFrame: Day one
measure: the Paced Auditory Serial Addition Task (PASAT)
timeFrame: Day three
measure: the Paced Auditory Serial Addition Task (PASAT)
timeFrame: One month
Locations:
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Antonia S. New, MD
role: PRINCIPAL_INVESTIGATOR
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citation: Kirrane RM, Mitropoulou V, Nunn M, New AS, Harvey PD, Schopick F, Silverman J, Siever LJ. Effects of amphetamine on visuospatial working memory performance in schizophrenia spectrum personality disorder. Neuropsychopharmacology. 2000 Jan;22(1):14-8. doi: 10.1016/S0893-133X(99)00075-5.
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