Idiopathic Parkinson's Progression and Dopamine Transporter SPECT
Condition: Parkinson Disease
MeSH terms: Parkinson Disease
Study type: Observational

Summary: 
      DaTscanTM Ioflupane I123, a radiopharmaceutical will be used as an adjunct diagnostic tool in
      combination with single photon emission computed tomography (SPECT) to evaluate striatal
      dopamine transporter (DAT) distribution in patients with idiopathic Parkinson's disease.
      Patients will be monitored twice - once at baseline, and again after 1 year - to identify
      potential biomarkers for progression of Parkinson's disease.
    

Detailed description: 
      Background: Idiopathic Parkinson's disease (PD) is a neurodegenerative disorder involving
      loss of dopaminergic neurons in the substantia nigra and subsequent dysfunction in the
      striatum. The diagnosis of PD remains a clinical diagnosis based on patient history and
      physical exam findings. In 2011 the FDA approved the use of DaTscanTM Ioflupane I123, a
      radiopharmaceutical to be used as an adjunct diagnostic tool in combination with single
      photon emission computed tomography (SPECT) to evaluate striatal dopamine transporter (DAT)
      distribution in patients with an unclear diagnosis of parkinsonism vs essential tremor (Bajaj
      et al., 2013). Because the loss of DAT binding in the striatum reflects the loss of
      dopaminergic neurons in parkinsonism, DAT SPECT is considered a highly sensitive test for
      these disorders (Ba and Martin, 2015). The major clinical uncertainty with DAT SPECT imaging
      is whether or not quantitative analysis can be utilized to determine progressive degeneration
      over time and serve as a quantitative biomarker for changes in striatal dopaminergic
      integrity in correlation with clinical worsening in patients with idiopathic PD. In 3 small
      studies using two other ligands, 18F-dopa and I123β-CIT, striatal uptake declined annually by
      12.5-13%, and 2.4% - 7.1%, respectively (Morrish et al., 1996; Nurmi et al., 2000; Pirker et
      al., 2012). Current analytical methodologies have focused on establishing differences between
      the PD and control groups, but have not explored the technology for tracking disease
      progression with Ioflupane I123, using the patient as their own control. The goal of this
      proposed study is to evaluate the validity of quantitative measurements in DAT SPECT scans in
      determining disease progression in subjects with idiopathic PD. Data from this pilot study
      would contribute significantly to future applications for investigating translational
      research strategies to restore dopaminergic cell function in PD. More specifically, the
      ability of autologous peripheral nerve grafts, acting as a source of neuroregenerative growth
      factors, is being investigated in PD subjects undergoing deep brain stimulation (Craig van
      Horne, PI). As there are no current biomarkers for PD progression, it is critical to evaluate
      the potential for DAT SPECT to serve as an analytical tool for the quantification of
      dopaminergic functional integrity. This study is designed to test the ability of DAT SPECT to
      be used as an effective methodology for tracking disease progression where patients serve as
      their own control.

      Objectives: The specific aim is to evaluate the ability of DAT SPECT quantification to track
      disease progression in subjects with idiopathic Parkinson's disease by comparing baseline
      scans to those obtained 12 months later. The quantified DAT SPECT data will be clinically
      correlated to the Movement Disorder Society Unified Parkinson's Disease Rating Scale
      (MDS-UPDRS) motor scores and Hoehn and Yahr stage obtained at baseline and at 12 months.

      Study Design: This will be an initial phase of a prospective study evaluating DAT SPECT
      quantification in subjects with idiopathic Parkinson's disease. The clinical severity of PD
      will be measured by MDS-UPDRS motor scores and the Hoehn and Yahr scale. Data will be
      acquired at baseline, and 12 months. The subject will serve as their own control.
    

Intervention name(s): Ioflupane I 123
Intervention type(s): Drug
Intervention description(s): Ioflupane I 123 will be administered IV push prior to SPECT imaging
Other intervention name(s): DaTscan
Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Subjects to be recruited during office visits at the University of Kentucky.
      
Keywords: dopamine transporter binding