Common Noradrenergic Mechanisms in Parkinson´s Disease and L-DOPA Induced Dyskinesia

• Status: Unknown status
• Trial end date: 2016-01-01
• Target enrollment: 0
• Participant gender: All

Summary

The aims of this proposal include tests of hypotheses of the pathogenetic mechanisms of noradrenergic neurotransmission in Parkinson's disease in vivo, using positron emission tomography of patients with early and advanced Parkinson's disease with or without 3,4 L-dihydroxyphenylalanine (L-DOPA) - induced dyskinesia or co-morbid depression, and evaluation of whether these mechanisms can be influenced therapeutically.

Hypotheses:

1. The investigators argue that release in human cortical and subcortical brain regions of norepinephrine (NE) derived from metabolism of exogenousL-DOPA is greater in Parkinson's disease patients with L-DOPA- induced dyskinesia than in patients without this complication. This hypothesis will be tested by measuring antagonist [11C]yohimbine binding to alpha-2 adrenoceptors before and after L-DOPA challenge.

2. If so, it is argued that the greater rise of norepinephrine, measured as [11C]yohimbine displacement after L-DOPA challenge, is the result of down-regulation or loss of norepinephrine transporters. This hypothesis will be tested by measuring the binding of [11C]MeNER, a tracer of norepinephrine transporters.

3. If so, the investigators argue that the greater decline of [11C]MeNER binding is significantly correlated to the symptoms of Parkinson's disease, as proof that patients with more severe loss of noradrenergic terminals exhibit more severe motor deficits.

• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Aarhus University Hospital
• Collaborator: University of Copenhagen
• Treatments: Carbidopa, levodopa drug combination; Levodopa; Yohimbine

Criteria

Inclusion Criteria:

• 15 patients with PD in the age between 50 og 80, Hoehn og Yahr stage 2-3, never L-DOPA induced dyskinesia.

• 15 patients with PD in the age between 50 og 80 år, Hoehn og Yahr stage 2-3, with established L-DOPA induced dyskinesia.

• 15 age matched healthy controls.

Exclusion Criteria:

• Psychiatric or neurological disease, not related to Parkinson´s disease.

• Cancer and malignant disease.

• Liver or kidney disease.

• Alcohol or substance abuse.

• Cardiac disease.

• Treatment with antipsychotics or antiepileptics or other medications that affect the noradrenergic system. Medicines to treat Parkinson´s disease are allowed.

• Patients treated with deep brain stimulation.