search
Back to results

A D1 Agonist For Working Memory

Primary Purpose

Schizotypal Personality Disorder, SPD

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
DAR 0-100A
Placebo
Sponsored by
Antonia New
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Schizotypal Personality Disorder focused on measuring schizotypal personality disorder, cognitive impairment, working memory, Dopamine Agonists, Cognition Disorders, Personality Disorders, Delirium, Dementia, Amnestic, Cognitive Disorders, Mental Disorders, Dihydrexidine, Dopamine A

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • Icahn School of Medicine at Mount Sinai

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

No Intervention

Arm Label

DAR 0-100A then Placebo

Placebo then DAR 0-100A

Healthy Control

Arm Description

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).

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).

patients without diagnosis of SPD

Outcomes

Primary Outcome Measures

The Modified AX-CPT (d')
A cognitive test of working memory

Secondary Outcome Measures

The Modified AX-CPT (d')
A cognitive test of working memory
The Modified AX-CPT (d')
A cognitive test of working memory
The Modified AX-CPT (d')
A cognitive test of working memory

Full Information

First Posted
July 22, 2015
Last Updated
April 5, 2018
Sponsor
Antonia New
Collaborators
New York State Psychiatric Institute, National Institute of Mental Health (NIMH)
search

1. Study Identification

Unique Protocol Identification Number
NCT02507206
Brief Title
A D1 Agonist For Working Memory
Official Title
A D1 Agonist For Working Memory Enhancement In The Schizophrenia Spectrum
Study Type
Interventional

2. Study Status

Record Verification Date
April 2018
Overall Recruitment Status
Completed
Study Start Date
April 2013 (undefined)
Primary Completion Date
January 12, 2018 (Actual)
Study Completion Date
January 12, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Antonia New
Collaborators
New York State Psychiatric Institute, National Institute of Mental Health (NIMH)

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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: 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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare Provider
Allocation
Randomized
Enrollment
120 (Actual)

8. Arms, Groups, and Interventions

Arm Title
DAR 0-100A then Placebo
Arm Type
Experimental
Arm Description
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).
Arm Title
Placebo then DAR 0-100A
Arm Type
Placebo Comparator
Arm Description
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).
Arm Title
Healthy Control
Arm Type
No Intervention
Arm Description
patients without diagnosis of SPD
Intervention Type
Drug
Intervention Name(s)
DAR 0-100A
Other Intervention Name(s)
DHX, dihydrexidine
Intervention Description
15 mg DAR 0100A is dissolved in 150 cc NS administered over 30 minutes intravenously.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
15 mg DAR placebo is dissolved in 150 cc NS administered over 30 minutes intravenously.
Primary Outcome Measure Information:
Title
The Modified AX-CPT (d')
Description
A cognitive test of working memory
Time Frame
Baseline performance
Secondary Outcome Measure Information:
Title
The Modified AX-CPT (d')
Description
A cognitive test of working memory
Time Frame
Day one
Title
The Modified AX-CPT (d')
Description
A cognitive test of working memory
Time Frame
Day three
Title
The Modified AX-CPT (d')
Description
A cognitive test of working memory
Time Frame
One month
Other Pre-specified Outcome Measures:
Title
the N-Back
Description
A cognitive tests of working memory - the N-Back (% correct at the 2-back condition)
Time Frame
Baseline
Title
the N-Back
Description
A cognitive tests of working memory - the N-Back (% correct at the 2-back condition)
Time Frame
Day one
Title
the N-Back
Description
A cognitive tests of working memory - the N-Back (% correct at the 2-back condition)
Time Frame
Day three
Title
the N-Back
Description
A cognitive tests of working memory - the N-Back (% correct at the 2-back condition)
Time Frame
One month
Title
the DOT Task
Description
A cognitive tests of working memory - the DOT Task (distance error at 30 second delay--no delay)
Time Frame
Baseline
Title
the DOT Task
Description
A cognitive tests of working memory - the DOT Task (distance error at 30 second delay--no delay)
Time Frame
Day one
Title
the DOT Task
Description
A cognitive tests of working memory - the DOT Task (distance error at 30 second delay--no delay)
Time Frame
Day three
Title
the DOT Task
Description
A cognitive tests of working memory - the DOT Task (distance error at 30 second delay--no delay)
Time Frame
One month
Title
the Paced Auditory Serial Addition Task (PASAT)
Description
A cognitive tests of working memory - the Paced Auditory Serial Addition Task
Time Frame
Baseline
Title
the Paced Auditory Serial Addition Task (PASAT)
Description
A cognitive tests of working memory - the Paced Auditory Serial Addition Task
Time Frame
Day one
Title
the Paced Auditory Serial Addition Task (PASAT)
Description
A cognitive tests of working memory - the Paced Auditory Serial Addition Task
Time Frame
Day three
Title
the Paced Auditory Serial Addition Task (PASAT)
Description
A cognitive tests of working memory - the Paced Auditory Serial Addition Task
Time Frame
One month

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Antonia S. New, MD
Organizational Affiliation
Icahn School of Medicine at Mount Sinai
Official's Role
Principal Investigator
Facility Information:
Facility Name
Icahn School of Medicine at Mount Sinai
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
7862943
Citation
Arnsten AF, Cai JX, Murphy BL, Goldman-Rakic PS. Dopamine D1 receptor mechanisms in the cognitive performance of young adult and aged monkeys. Psychopharmacology (Berl). 1994 Oct;116(2):143-51. doi: 10.1007/BF02245056.
Results Reference
background
PubMed Identifier
16946930
Citation
Abi-Dargham A. Probing cortical dopamine function in schizophrenia: what can D1 receptors tell us? World Psychiatry. 2003 Oct;2(3):166-71.
Results Reference
background
PubMed Identifier
10720329
Citation
Castner SA, Williams GV, Goldman-Rakic PS. Reversal of antipsychotic-induced working memory deficits by short-term dopamine D1 receptor stimulation. Science. 2000 Mar 17;287(5460):2020-2. doi: 10.1126/science.287.5460.2020.
Results Reference
background
PubMed Identifier
9126882
Citation
Fici GJ, Wu H, VonVoigtlander PF, Sethy VH. D1 dopamine receptor activity of anti-parkinsonian drugs. Life Sci. 1997;60(18):1597-603. doi: 10.1016/s0024-3205(97)00126-4.
Results Reference
background
PubMed Identifier
10633486
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.
Results Reference
background
PubMed Identifier
12823075
Citation
Koenigsberg HW, Reynolds D, Goodman M, New AS, Mitropoulou V, Trestman RL, Silverman J, Siever LJ. Risperidone in the treatment of schizotypal personality disorder. J Clin Psychiatry. 2003 Jun;64(6):628-34. doi: 10.4088/jcp.v64n0602.
Results Reference
background

Learn more about this trial

A D1 Agonist For Working Memory

We'll reach out to this number within 24 hrs