Clinical Trial: Clinical Testing of a D1 Agonist for Cognitive Enhancement in Schizotypal Personality Disorder

Study Status: Completed
Recruit Status: Unknown status
Study Type: Interventional

Official Title: Clinical Testing of a D1 Agonist for Cognitive Enhancement in Schizotypal Personality Disorder

Brief Summary:

Currently, no study to date has directly tested a selective D1R agonist in relation to the cognitive impairment of Schizophrenia without the confound of neuroleptics. The investigators propose to examine the efficacy of DAR-0100A, a highly selective, full D1R agonist supported by pre-clinical and preliminary pilot clinical data, in ameliorating the cognitive deficits in Schizotypal Personality Disordered subjects receiving no medications including antipsychotics.

The investigators hypothesize that 1) Baseline primary outcome measures will be impaired in Schizotypal personality disorder (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, and 3) SPD patients will show significant improvements on primary outcome variables on drug compared to placebo.


Detailed Summary:

Working memory deficits are central to the cognitive impairment of schizophrenia and other psychiatric disorders. The D1 receptor (D1R) is probably the best established mediator of working memory in neuroscience studies for over three decades and represents a highly promising therapeutic target for enhancing working memory in these disorders, yet this mechanism has never been tested in humans. Schizotypal personality disorder (SPD) patients who evidence moderate, focal impairments in working memory represent a unique population to test the effect of a D1 agonist on working memory impairment in humans. Cognitive impairment is the most salient predictor of functional outcome in schizophrenia (SCZ) and is essentially refractory to conventional treatments. Identifying pharmacologic agents that target the cognitive deficits of SCZ is thus the top priority in SCZ research, but so far, clinical trials of a number of drugs with preclinical promise have yielded disappointing results. Currently, no study to date has directly tested a selective D1R agonist in relation to the cognitive impairment of SCZ without the confound of neuroleptics. The investigators propose to examine the efficacy of DAR-0100A, a highly selective, full D1R agonist supported by pre-clinical and preliminary pilot clinical data, in ameliorating the cognitive deficits in SPD subjects receiving no medications including antipsychotics. SPD will be classified as a schizophrenic disorder in DSM-5 and ICD-10. The investigators have characterized the cognitive deficits of SPD and demonstrated that, as with chronic SCZ, a core component consists of impairments in working memory. Studies of SPD obviate confounds associated with SCZ, such as the effects of overt psychotic episodes, medication history, severe, persistent functional impairment and multiple treatments. Furthermore, the cognitive deficits of SPD are less global and more readily reversible than those of chro
Sponsor: Larry J. Siever

Current Primary Outcome:

  • Efficacy of a D1 Agonist for Cognitive Enhancement of Working Memory in Schizotypal Personality Disorder [ Time Frame: Baseline performance ]
    The cognitive tests of working memory serving as primary outcome measures will include the modified AX-CPT (d'), the N-Back (% correct at the 2-back condition), the DOT Task (distance error at 30 second delay--no delay), and the Paced Auditory Serial Addition Task (PASAT)(correct responses).
  • Efficacy of a D1 Agonist for Cognitive Enhancement of Working Memory in Schizotypal Personality Disorder [ Time Frame: day one of drug administration ]
    The cognitive tests of working memory serving as primary outcome measures will include the modified AX-CPT (d'), the N-Back (% correct at the 2-back condition), the DOT Task (distance error at 30 second delay--no delay), and the Paced Auditory Serial Addition Task (PASAT)(correct responses).
  • Efficacy of a D1 Agonist for Cognitive Enhancement of Working Memory in Schizotypal Personality Disorder [ Time Frame: after three days of drug administration ]
    The cognitive tests of working memory serving as primary outcome measures will include the modified AX-CPT (d'), the N-Back (% correct at the 2-back condition), the DOT Task (distance error at 30 second delay--no delay), and the Paced Auditory Serial Addition Task (PASAT)(correct responses).
  • Efficacy of a D1 Agonist for Cognitive Enhancement of Working Memory in Schizotypal Personality Disorder [ Time Frame: one month after drug administration ]
    The cognitive tests of working memory servin

    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    Original Secondary Outcome:

    Information By: Icahn School of Medicine at Mount Sinai

    Dates:
    Date Received: October 27, 2011
    Date Started: January 2011
    Date Completion: January 2013
    Last Updated: July 19, 2012
    Last Verified: July 2012