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

This study has been completed.
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Alexander Storch, Dresden University of Technology
ClinicalTrials.gov Identifier:
NCT00153972
First received: September 7, 2005
Last updated: December 17, 2012
Last verified: December 2012
  Purpose

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.


Condition Intervention Phase
Parkinson's Disease
Drug: Cabergoline
Drug: Levodopa
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Investigator)
Primary Purpose: Treatment
Official Title: Dopamine Turnover Rate Measured With F-Dopa-PET as Surrogate Parameter for Diagnosis and Progression Analysis of Early Parkinson's Disease

Resource links provided by NLM:


Further study details as provided by Technische Universität Dresden:

Primary Outcome Measures:
  • 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:
  • Changes of clinical outcome measured with parkinsonian rating scales (UPDRS, PDQ-39, ESS, olfactory function)

Enrollment: 39
Study Start Date: February 2005
Study Completion Date: January 2009
Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Levodopa
Levodopa 300 mg per day orally.
Drug: Cabergoline Drug: Levodopa
Active Comparator: Cabergoline
Cabergoline 3 mg per day orally.
Drug: Cabergoline Drug: Levodopa

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

Ages Eligible for Study:   40 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00153972

Locations
Germany
Department of Neurology at the Technical University of Dresden
Dresden, Saxony, Germany, 01307
Department of Nuclear Medicine at the Technical University of Dresden
Dresden, Saxony, Germany, 01307
Sponsors and Collaborators
Technische Universität Dresden
Pfizer
Investigators
Principal Investigator: Heinz Reichmann, MD Technical University of Dresden
  More Information

Additional Information:
Publications:
Responsible Party: Alexander Storch, Professor, Dresden University of Technology
ClinicalTrials.gov Identifier: NCT00153972     History of Changes
Other Study ID Numbers: 91052003
Study First Received: September 7, 2005
Last Updated: December 17, 2012
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Technische Universität Dresden:
Parkinson's disease
Fluoro-Dopa-PET
Dopamine agonists
Cabergoline
Surrogate marker
Dopamine turnover

Additional relevant MeSH terms:
Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Dopamine
Dopamine Agents
Levodopa
Cabergoline
Cardiotonic Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Protective Agents
Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents
Antineoplastic Agents
Dopamine Agonists

ClinicalTrials.gov processed this record on August 26, 2014