Pharmacologic and Clinical Testing of a D1 Agonist for Cognitive Enhancement in Neuropsychiatric Disorders
Condition: Schizophrenia; Schizoaffective Disorder
MeSH terms: Schizophrenia; Psychotic Disorders
Study type: Interventional
Phase: Early Phase 1

Summary: 
      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.
    

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.
    

Intervention name(s): DAR-100A; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 15mg or 0.5mg of DAR-100A intravenously over 30 minutes for 5 days, 9 days off then again for 5 more days; Placebo
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment