A D1 Agonist For Working Memory

Sponsor

Antonia New (Other)

Overall Status

Completed

CT.gov ID

NCT02507206

Collaborator

New York State Psychiatric Institute (Other), National Institute of Mental Health (NIMH) (NIH)

120

Enrollment

Location

Arms

57.4

Duration (Months)

2.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Schizotypal Personality Disorder SPD	Drug: DAR 0-100A Drug: Placebo	Phase 2

Detailed Description

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.
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).

Study Design

Study Type:

Interventional

Actual Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Double (Participant, Care Provider)

Primary Purpose:

Treatment

Official Title:

A D1 Agonist For Working Memory Enhancement In The Schizophrenia Spectrum

Study Start Date :

Apr 1, 2013

Actual Primary Completion Date :

Jan 12, 2018

Actual Study Completion Date :

Jan 12, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: DAR 0-100A then Placebo 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 15 mg DAR 0100A is dissolved in 150 cc NS administered over 30 minutes intravenously. Other Names: DHX dihydrexidine Drug: Placebo 15 mg DAR placebo is dissolved in 150 cc NS administered over 30 minutes intravenously.
Placebo Comparator: Placebo then DAR 0-100A 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 15 mg DAR 0100A is dissolved in 150 cc NS administered over 30 minutes intravenously. Other Names: DHX dihydrexidine Drug: Placebo 15 mg DAR placebo is dissolved in 150 cc NS administered over 30 minutes intravenously.
No Intervention: Healthy Control patients without diagnosis of SPD

Arm

Intervention/Treatment

Experimental: DAR 0-100A then Placebo

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

15 mg DAR 0100A is dissolved in 150 cc NS administered over 30 minutes intravenously.

Other Names:

DHX

dihydrexidine

Drug: Placebo

15 mg DAR placebo is dissolved in 150 cc NS administered over 30 minutes intravenously.

Placebo Comparator: Placebo then DAR 0-100A

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

15 mg DAR 0100A is dissolved in 150 cc NS administered over 30 minutes intravenously.

Other Names:

DHX

dihydrexidine

Drug: Placebo

15 mg DAR placebo is dissolved in 150 cc NS administered over 30 minutes intravenously.

No Intervention: Healthy Control

patients without diagnosis of SPD

Outcome Measures

Primary Outcome Measures

The Modified AX-CPT (d') [Baseline performance]
A cognitive test of working memory

Secondary Outcome Measures

The Modified AX-CPT (d') [Day one]
A cognitive test of working memory
The Modified AX-CPT (d') [Day three]
A cognitive test of working memory
The Modified AX-CPT (d') [One month]
A cognitive test of working memory

Other Outcome Measures

the N-Back [Baseline]
A cognitive tests of working memory - the N-Back (% correct at the 2-back condition)
the N-Back [Day one]
A cognitive tests of working memory - the N-Back (% correct at the 2-back condition)
the N-Back [Day three]
A cognitive tests of working memory - the N-Back (% correct at the 2-back condition)
the N-Back [One month]
A cognitive tests of working memory - the N-Back (% correct at the 2-back condition)
the DOT Task [Baseline]
A cognitive tests of working memory - the DOT Task (distance error at 30 second delay--no delay)
the DOT Task [Day one]
A cognitive tests of working memory - the DOT Task (distance error at 30 second delay--no delay)
the DOT Task [Day three]
A cognitive tests of working memory - the DOT Task (distance error at 30 second delay--no delay)
the DOT Task [One month]
A cognitive tests of working memory - the DOT Task (distance error at 30 second delay--no delay)
the Paced Auditory Serial Addition Task (PASAT) [Baseline]
A cognitive tests of working memory - the Paced Auditory Serial Addition Task
the Paced Auditory Serial Addition Task (PASAT) [Day one]
A cognitive tests of working memory - the Paced Auditory Serial Addition Task
the Paced Auditory Serial Addition Task (PASAT) [Day three]
A cognitive tests of working memory - the Paced Auditory Serial Addition Task
the Paced Auditory Serial Addition Task (PASAT) [One month]
A cognitive tests of working memory - the Paced Auditory Serial Addition Task

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.