Pharmacologic and Clinical Testing of a D1 Agonist for Cognitive Enhancement in Neuropsychiatric Disorders

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
New York State Psychiatric Institute
ClinicalTrials.gov Identifier:
NCT01519557
First received: January 13, 2012
Last updated: December 19, 2013
Last verified: December 2013
  Purpose

The investigators propose to recruit individuals with schizophrenia who are symptomatically stable and already taking medications to participate in this study. The investigators will recruit 90 individuals with schizophrenia and randomize them to low and high doses of DAR-0100A, as well as to placebo. The investigators will have them stay in the hospital for several weeks and receive up to 10 doses of DAR-0100A. The investigators will also test their cognition before and after receiving DAR-0100A to see if DAR-0100A is helpful and perform MRI scans before and after taking the medication to see which areas of the brain are activated when DAR-0100A is administered. These tests will be very important because they will help the investigators determine whether the D1 receptor is a good treatment target for schizophrenia and whether more research and resources should be devoted to finding medications that target this system.

Patients with schizophrenia will be free of other medical, psychiatric and neurological disorders including alcohol and substance dependence, and will be able to understand the nature of the study and to provide informed consent.


Condition Intervention Phase
Schizophrenia
Schizoaffective Disorder
Drug: DAR-100A
Drug: Placebo
Phase 0

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Pharmacologic and Clinical Testing of a D1 Agonist for Cognitive Enhancement in Neuropsychiatric Disorders

Resource links provided by NLM:


Further study details as provided by New York State Psychiatric Institute:

Primary Outcome Measures:
  • Change from Baseline in resting blood flow and neural activity during working memory tasks in the dorsolateral prefrontal cortex (DLPFC)after 5 days study drug administration. [ Time Frame: Day 0 (baseline) and Day 5 ] [ Designated as safety issue: No ]
    The investigators will measure neural activity during working memory (WM) tasks using blood-oxygen-level-dependent (BOLD)contrast function magnetic resonance imaging (fMRI) and the n-back task and self-ordered object working memory task (SOWMT), prior to (day 0, baseline) and after receiving sub-acute (day 5) treatment with DAR-0100A (15mg or 0.5mg) or placebo.

  • Change from Baseline in resting blood flow and neural activity during working memory tasks in the dorsolateral prefrontal cortex (DLPFC)after 5 days study drug administration. [ Time Frame: Day 0 (baseline) and Day 5 ] [ Designated as safety issue: No ]
    The investigators will measure neural activity during working memory (WM) tasks using blood-oxygen-level-dependent (BOLD)contrast function magnetic resonance imaging(fMRI) and the n-back task and self-ordered object working memory task (SOWMT), prior to (day 0, baseline) and after receiving sub-acute (day 5) treatment with DAR-0100A (15mg or 0.5mg) or placebo.


Secondary Outcome Measures:
  • Change from Baseline in cognitive performance after 5 days study drug administration. [ Time Frame: Patients will be tested at baseline and after repeated administration of DAR-0100A or placebo, and 3 months after the cessation of treatment with the D1 agonist ] [ Designated as safety issue: No ]
    The main outcome measures will be the change in composite score on the MATRICS Consensus Cognitive Battery (MCCB) and CogState Schizophrenia Test batteries from baseline(Day 0) and after repeated administration of DAR-0100A or placebo (Day 5). These batteries are also designed to be repeatable (insensitive to practice effects)and to allow for measurements of changes in performance (no floor or ceiling effects).


Enrollment: 68
Study Start Date: April 2011
Estimated Study Completion Date: December 2014
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: DAR-100A
DAR-0100A is a dopamine D1 full agonist, the active component of the racemic mixture DAR-0100
Drug: DAR-100A
15mg or 0.5mg of DAR-100A intravenously over 30 minutes for 5 days, 9 days off then again for 5 more days
Placebo Comparator: Placebo
Intravenously over 30 minutes for 5 days, 9 days off then again for 5 more days
Drug: Placebo
Placebo

Detailed Description:

Schizophrenia (SCZ) manifests as positive symptoms, negative symptoms and cognitive disturbances. To date, all of the available medications to treat schizophrenia bind primarily to the dopamine-2 (D2) receptor in the brain, and are only effective at treating the positive symptoms of schizophrenia. This is unfortunate given that negative and cognitive symptoms account for most of the disability in schizophrenia.

Emerging research over the past several decades has suggested a potential role for the dopamine-1 (D1) receptor in schizophrenia, as well as a role for D1 receptor stimulation in improving cognitive deficits. DAR-0100A is a new medication that binds selectively to the D1 receptor. It has been found to be safe when given to individuals with schizophrenia, and preliminary data suggests that it may be able to help with cognitive deficits.

The investigators propose to recruit individuals with schizophrenia who are symptomatically stable and already taking medications to participate in this study. The investigators will recruit 90 individuals with schizophrenia and randomize them to low and high doses of DAR-0100A, as well as to placebo. Patients will stay in the hospital for several weeks and receive up to 10 doses of DAR-0100A. The investigators will also test their cognition before and after receiving DAR-0100A to see if DAR-0100A is helpful and perform MRI scans before and after taking the medication to see which areas of the brain are activated when DAR-0100A is administered. These tests will be very important because they will help the investigators determine whether the D1 receptor is a good treatment target for schizophrenia and whether more research and resources should be devoted to finding medications that target this system.

Patients with schizophrenia will be free of other medical, psychiatric and neurological disorders including alcohol and substance dependence, and will be able to understand the nature of the study and to provide informed consent.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Males or females between 18 and 55 years old
  • Fulfill Diagnostic and Statistical Manual, version 4 (DSM-IV) criteria schizophrenic illness, schizophreniform or schizoaffective disorder
  • A negative urine toxicology
  • Capacity to understand the study and to give written informed consent
  • Must be on a stable dose of risperidone, aripiprazole, lurasidone, iloperidone, paliperidone, or haloperidol for at least 4 weeks if oral adn 2 cycles if depot. Absence of any antipsychotic medications other than risperidone, aripiprazole, or haloperidol for at least 4 weeks if oral or 2 cycles if depot prior to the study. Mood stabilizers, benzodiazepines and antidepressants are allowed as long as the drugs have not been changed for 4 weeks.
  • Psychiatrically stable

Exclusion Criteria:

  • Pregnancy or lactation, lack of effective birth control during the 15 days before the initial day of the study and for the duration of the drug trial
  • Presence or positive history of severe medical or neurological illness, or any cardiovascular or liver disease
  • Any current use of amphetamines, opiates, cocaine, sedative-hypnotics, cannabis, or other psychoactive drugs (other than nicotine)
  • Metal implants or paramagnetic objects contained within the body which may interfere with MRI scan
  • A history of substance dependence (other than nicotine or cannabis) or substance abuse within the previous 6 months (other than nicotine)
  • Any current use of anticholinergic or anticoagulant medications. Any current use of any medications that can affect cognition or clotting other than occasional nonsteroidal antiinflammatory drug (NSAID)
  • Impaired intellectual functioning
  • Orthostatic hypotension
  • BP systolic BP <90 or > 140 or diastolic BP < 60 or > 90
  • Antipsychotic polypharmacy within the previous four weeks.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01519557

Locations
United States, New York
New York State Psychiatric Institute
New York, New York, United States, 10032
Sponsors and Collaborators
New York State Psychiatric Institute
Investigators
Principal Investigator: Jeffrey A Lieberman, M.D. New York State Psychiatric Institute
  More Information

No publications provided

Responsible Party: New York State Psychiatric Institute
ClinicalTrials.gov Identifier: NCT01519557     History of Changes
Other Study ID Numbers: #6329, UO1MH76544-03
Study First Received: January 13, 2012
Last Updated: December 19, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Psychotic Disorders
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders

ClinicalTrials.gov processed this record on August 20, 2014