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Dopamine Turnover Rate as Surrogate Parameter for Diagnosis of Early Parkinson's Disease

Phase 4
Completed
Conditions
Parkinson's Disease
Interventions
Registration Number
NCT00153972
Lead Sponsor
Technische Universität Dresden
Brief 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)

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
39
Inclusion Criteria
  • Early (de novo) Parkinson's disease (Hoen & Yahr I and II), according to the UK brain bank criteria
Exclusion Criteria
  • Current or past dopaminergic treatment
  • Atypical parkinsonian syndromes
  • Treatment with neuroleptics (present and past)
  • Pregnancy

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
LevodopaCabergolineLevodopa 300 mg per day orally.
LevodopaLevodopaLevodopa 300 mg per day orally.
CabergolineCabergolineCabergoline 3 mg per day orally.
CabergolineLevodopaCabergoline 3 mg per day orally.
Primary Outcome Measures
NameTimeMethod
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.
Secondary Outcome Measures
NameTimeMethod
Changes of clinical outcome measured with parkinsonian rating scales (UPDRS, PDQ-39, ESS, olfactory function)

Trial Locations

Locations (2)

Department of Nuclear Medicine at the Technical University of Dresden

🇩🇪

Dresden, Saxony, Germany

Department of Neurology at the Technical University of Dresden

🇩🇪

Dresden, Saxony, Germany

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