A D1 Agonist For Working Memory

Schizotypal Personality Disorder Clinical Trial

Official title:

A D1 Agonist For Working Memory Enhancement In The Schizophrenia Spectrum

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02507206
• Other study ID #: GCO 11-1279
• Secondary ID: 5R01MH097799-02
• Status: Completed
• Phase: Phase 2
• First received: July 22, 2015
• Last updated: April 5, 2018
• Start date: April 2013
• Est. completion date: January 12, 2018

Study information

• Verified date: April 2018
• Source: Icahn School of Medicine at Mount Sinai
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: January 12, 2018
• Est. primary completion date: January 12, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Personality Disorders
• Schizotypal Personality Disorder
• SPD

Intervention

Drug:
• DAR 0-100A
15 mg DAR 0100A is dissolved in 150 cc NS administered over 30 minutes intravenously.
• Placebo
15 mg DAR placebo is dissolved in 150 cc NS administered over 30 minutes intravenously.

Locations

Country	Name	City	State
United States	Icahn School of Medicine at Mount Sinai	New York	New York

Sponsors (3)

Lead Sponsor	Collaborator
Antonia New	National Institute of Mental Health (NIMH), New York State Psychiatric Institute

Country where clinical trial is conducted

United States, 

References & Publications (6)

Abi-Dargham A. Probing cortical dopamine function in schizophrenia: what can D1 receptors tell us? World Psychiatry. 2003 Oct;2(3):166-71. — View 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. — View 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. — View Citation

Fici GJ, Wu H, VonVoigtlander PF, Sethy VH. D1 dopamine receptor activity of anti-parkinsonian drugs. Life Sci. 1997;60(18):1597-603. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	the N-Back	A cognitive tests of working memory - the N-Back (% correct at the 2-back condition)	Baseline
Other	the N-Back	A cognitive tests of working memory - the N-Back (% correct at the 2-back condition)	Day one
Other	the N-Back	A cognitive tests of working memory - the N-Back (% correct at the 2-back condition)	Day three
Other	the N-Back	A cognitive tests of working memory - the N-Back (% correct at the 2-back condition)	One month
Other	the DOT Task	A cognitive tests of working memory - the DOT Task (distance error at 30 second delay--no delay)	Baseline
Other	the DOT Task	A cognitive tests of working memory - the DOT Task (distance error at 30 second delay--no delay)	Day one
Other	the DOT Task	A cognitive tests of working memory - the DOT Task (distance error at 30 second delay--no delay)	Day three
Other	the DOT Task	A cognitive tests of working memory - the DOT Task (distance error at 30 second delay--no delay)	One month
Other	the Paced Auditory Serial Addition Task (PASAT)	A cognitive tests of working memory - the Paced Auditory Serial Addition Task	Baseline
Other	the Paced Auditory Serial Addition Task (PASAT)	A cognitive tests of working memory - the Paced Auditory Serial Addition Task	Day one
Other	the Paced Auditory Serial Addition Task (PASAT)	A cognitive tests of working memory - the Paced Auditory Serial Addition Task	Day three
Other	the Paced Auditory Serial Addition Task (PASAT)	A cognitive tests of working memory - the Paced Auditory Serial Addition Task	One month
Primary	The Modified AX-CPT (d')	A cognitive test of working memory	Baseline performance
Secondary	The Modified AX-CPT (d')	A cognitive test of working memory	Day one
Secondary	The Modified AX-CPT (d')	A cognitive test of working memory	Day three
Secondary	The Modified AX-CPT (d')	A cognitive test of working memory	One month