Dopamine Transporter Neuroimaging as an Enrichment Biomarker in Early Parkinson's Disease Clinical Trials: A Disease Progression Modeling Analysis

Clin Transl Sci. 2018 Jan;11(1):63-70. doi: 10.1111/cts.12492. Epub 2017 Jul 27.


Given the recognition that disease-modifying therapies should focus on earlier Parkinson's disease stages, trial enrollment based purely on clinical criteria poses significant challenges. The goal herein was to determine the utility of dopamine transporter neuroimaging as an enrichment biomarker in early motor Parkinson's disease clinical trials. Patient-level longitudinal data of 672 subjects with early-stage Parkinson's disease in the Parkinson's Progression Markers Initiative (PPMI) observational study and the Parkinson Research Examination of CEP-1347 Trial (PRECEPT) clinical trial were utilized in a linear mixed-effects model analysis. The rate of worsening in the motor scores between subjects with or without a scan without evidence of dopamine transporter deficit was different both statistically and clinically. The average difference in the change from baseline of motor scores at 24 months between biomarker statuses was -3.16 (90% confidence interval [CI] = -0.96 to -5.42) points. Dopamine transporter imaging could identify subjects with a steeper worsening of the motor scores, allowing trial enrichment and 24% reduction of sample size.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / analysis
  • Brain / diagnostic imaging
  • Brain / metabolism
  • Disease Progression
  • Dopamine Plasma Membrane Transport Proteins / analysis*
  • Dopamine Plasma Membrane Transport Proteins / metabolism
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Models, Biological*
  • Molecular Imaging / methods*
  • Monte Carlo Method
  • Motor Activity / physiology
  • Neuroimaging / methods*
  • Parkinson Disease / diagnostic imaging*
  • Parkinson Disease / physiopathology
  • Patient Dropouts
  • Randomized Controlled Trials as Topic
  • Tomography, Emission-Computed, Single-Photon / methods


  • Biomarkers
  • Dopamine Plasma Membrane Transport Proteins