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

Study Overview
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Brief Summary
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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
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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)

Official Title
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Dopamine Turnover Rate Measured With F-Dopa-PET as Surrogate Parameter for Diagnosis and Progression Analysis of Early Parkinson's Disease

Conditions
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Parkinson's Disease

Intervention / Treatment
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* Drug: Cabergoline
* Drug: Levodopa


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Levodopa<br>Levodopa 300 mg per day orally. | Drug: Cabergoline<br> <br> Drug: Levodopa<br> <br> |
| Active Comparator: Cabergoline<br>Cabergoline 3 mg per day orally. | Drug: Cabergoline<br> <br> Drug: Levodopa<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of clinical outcome measured with parkinsonian rating scales (UPDRS, PDQ-39, ESS, olfactory function) |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parkinson's disease, Fluoro-Dopa-PET, Dopamine agonists, Cabergoline, Surrogate marker, Dopamine turnover