Dopamine Turnover Rate as Surrogate Parameter for Diagnosis of Early Parkinson's Disease
Condition: Parkinson's Disease
MeSH terms: Parkinson Disease
Study type: Interventional
Phase: Phase 4

Summary: 
      The study is designed to measure the difference of dopamine turnover rate measured by
      Fluoro-Dopa-PET in the putamen between patients with Parkinson's disease treated with
      cabergoline and levodopa for 3 months.

      The study protocol includes an initial Fluoro-Dopa-PET scan before treatment and after three
      months double-blind treatment with cabergoline or levodopa.

      The hypothesis for this study is that the dopamine turnover rate is a more sensitive marker
      for the early diagnosis of Parkinson's disease compared to the standard Fluoro-Dopa-PET
      measuring only the Fluoro-Dopa uptake into the striatum.

      For the interventional part of the study, the hypothesis is that levodopa has larger effects
      on striatal dopamine turnover compared to dopamine agonists by providing more dopamine
      precursor. Enhancement of compensatory mechanisms for dopamine loss in early PD such as
      increased dopamine turnover could have several beneficial implications such as improvement or
      prolongation of symptomatic treatment responses, but might also produce therapeutic problems
      such as the development of levodopa-induced motor complications.
    

Detailed description: 
      The study is designed to measure the difference of dopamine turnover rate measured by
      Fluoro-Dopa-PET in the putamen between patients with Parkinson's disease treated with
      cabergoline and levodopa for 3 months.

      The hypothesis for this study is that the dopamine turnover rate is a more sensitive marker
      for the early diagnosis of Parkinson's disease compared to the standard Fluoro-Dopa-PET
      measuring only the Fluoro-Dopa uptake into the striatum. The specific aim of the study was to
      estimate normal ranges and test-retest measures for various parameters characterising
      dopamine metabolism from a prolonged 18F-dopa positron emission tomography (PET) measurement
      using a reference tissue model and compare their value for the detection of early PD.

      For the interventional part of the study, the hypothesis is that levodopa has larger effects
      on striatal dopamine turnover compared to dopamine agonists by providing more dopamine
      precursor. Enhancement of compensatory mechanisms for dopamine loss in early PD such as
      increased dopamine turnover could have several beneficial implications such as improvement or
      prolongation of symptomatic treatment responses, but might also produce therapeutic problems
      such as the development of levodopa-induced motor complications. The specific aim is to
      evaluate the effects of levodopa and the dopamine D2 agonist cabergoline on striatal dopamine
      turnover estimated as the inverse of the effective dopamine distribution volume ratio (EDVR)
      measured by 18F-dopa PET in de-novo PD.

      The study protocol includes an initial Fluoro-Dopa-PET scan before treatment and after three
      months double-blind treatment with cabergoline or levodopa. This study is an
      investigator-blinded, randomized mono-center controlled phase IV study.

      The main inclusion criteria are:

      - Early (de novo) Parkinson's disease (Hoen & Yahr I and II), according to the UK brain bank
      criteria

      The main exclusion criteria are:

        -  Current or past dopaminergic treatment

        -  Atypical parkinsonian syndromes

        -  Treatment with neuroleptics (present and past)

      Methods:

        -  Fluoro-dopa-PET for measuring the dopamine turnover rate

        -  clinical investigations including parkinsonian rating scales (e.g. UPDRS, PDQ-39, etc.)

        -  olfactory tests

      Study medication:

        -  Cabergoline (1 to 3 mg once per day)

        -  Levodopa/carbidopa (50 until 300 mg levodopa per day in one to three dosages)
    

Intervention name(s): Cabergoline; Levodopa
Intervention type(s): Drug; Drug
Intervention MeSH terms: Levodopa; Cabergoline
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Investigator)
Primary purpose: Treatment
Keywords: Parkinson's disease; Fluoro-Dopa-PET; Dopamine agonists; Cabergoline; Surrogate marker; Dopamine turnover