Clinical trial NCT00153972: Dopamine Turnover Rate as Surrogate Parameter for Diagnosis of Early Parkinson's Disease
Official title: Dopamine Turnover Rate Measured With F-Dopa-PET as Surrogate Parameter for Diagnosis and Progression Analysis of Early Parkinson's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Parkinson's Disease
Keywords: Parkinson's disease
Fluoro-Dopa-PET
Dopamine agonists
Cabergoline
Surrogate marker
Dopamine turnover
Lead sponsor: Technische Universität Dresden
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2005-09-12
Enrollment: 39
Sex: ALL
Minimum age (years): 40
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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)

Eligibility criteria: 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

Primary outcomes:
measure: 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 outcomes:
measure: Changes of clinical outcome measured with parkinsonian rating scales (UPDRS, PDQ-39, ESS, olfactory function)
Other outcomes:
Locations:
city: Dresden
country: Germany
facility: Department of Neurology at the Technical University of Dresden
state: Saxony
city: Dresden
country: Germany
facility: Department of Nuclear Medicine at the Technical University of Dresden
state: Saxony
Study officials:
affiliation: Technical University of Dresden
name: Heinz Reichmann, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Oehme L, Perick M, Beuthien-Baumann B, Wolz M, Storch A, Lohle M, Herting B, Langner J, van den Hoff J, Reichmann H, Kotzerke J. Comparison of dopamine turnover, dopamine influx constant and activity ratio of striatum and occipital brain with (1)(8)F-dopa brain PET in normal controls and patients with Parkinson's disease. Eur J Nucl Med Mol Imaging. 2011 Aug;38(8):1550-9. doi: 10.1007/s00259-011-1819-8. Epub 2011 May 7.