Phosphorylation of ERK1/2 in Patients With Parkinson's Disease (BIODYS (1))

A Descriptive Study of Lymphocytic Phosphorylation of ERK1/2 in Patients With Parkinson's Disease With Dyskinesias and in Controls

Levodopa-induced dyskinesia severely limits the use of levodopa in Parkinson's disease and constitutes a debilitating complication of dopaminergic treatment in late stage. Among several neurobiological mechanisms identified so far, the investigators have established in experimental models the key role of D1 receptor hypersensitivity and a"Ras-ERK" signalling pathway. As the very same dopamine receptor machinery and the Ras-ERK pathway are present in blood lymphocytes, the investigators wish to test the hypothesis that the level of ERK phosphorylation in lymphocytes is a biomarker of levodopa-induced dyskinesia in Parkinson's Disease.

The study will be performed in dyskinetic levodopa-treated patients and non-Parkinson's Disease controls. Blood sampling "off" and "on" levodopa treatment (1 hour post-dose), as well as clinical data collection will be done during a scheduled pre-op work-up (deep brain stimulation). Subsequently, suspended lymphocytes from blood samples will be immunolabelled using an anti-pERK antibody and mean fluorescence intensity and percent of labelled lymphocytes will be assessed by flow cytometry. Additionally, plasma and urine samples will be collected "on" et "off" for dosage of dopamine. The motor effect of levodopa will be assessed through UPRSIII rating scale and eye movement (saccades) speed by non-invasive oculometric recordings.

Study Overview

• Status: Completed
• Conditions: Parkinson Disease
• Intervention / Treatment: Other: Clinical variables; Other: Clinical variables; Other: Clinical variables

• Study Type: Observational
• Enrollment (Actual): 30

Contacts and Locations

Study Locations

• France
  • Pessac, France, 33604
    • CHU de Bordeaux Hopital Haut leveque

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Consecutive eligible PD in- and outpatients selected at the university hospital of bordeaux and subjects without known neurological disorder in a community sample.

Description

Inclusion Criteria:

• Consecutive eligible PD in- and outpatients selected at the university hospital of Bordeaux.
• Non-demented patients (DSM IV) who are able to give their informed consent and who are affiliated to the social security.
• Controls: Subjects without known neurological disorder, non-demented, able to give their informed consent and affiliated to the social security.

Exclusion Criteria:

• Patients: Atypical or secondary parkinson disease.
• Previous or current cancer or malignant haemopathy.
• Known auto-immune disease.
• Anti-neoplastic or immuno-modulator treatment (particularly corticosteroids). Immuno-deficient subjects.
• Acute viral infection (within 2 weeks after resolving). Statin drug intake. Demented subject (DSMIV).
• Controls: Same criteria as above plus any neurological disease.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Parkinson's Disease patient; levodopa-treated parkinson's disease (PD) patients	Other: Clinical variables; Demography, disease duration, treatment duration, current treatment, daily intake of levodopa, Disease stage (Hoehn and Yahr, HY), motor score (UPDRS III) and dyskinesia severity (UPDRS IV). Biological variables.; Other: Clinical variables; Demography, Biological variables.; Other: Clinical variables; Eye movement recordings : non-invasive infra-red camera oculometry (EyeBrain) before and after (only parkinson's disease group) levodopa(10 to 15 minute/recording)
Non Parkinson's disease controls	Other: Clinical variables; Demography, disease duration, treatment duration, current treatment, daily intake of levodopa, Disease stage (Hoehn and Yahr, HY), motor score (UPDRS III) and dyskinesia severity (UPDRS IV). Biological variables.; Other: Clinical variables; Demography, Biological variables.; Other: Clinical variables; Eye movement recordings : non-invasive infra-red camera oculometry (EyeBrain) before and after (only parkinson's disease group) levodopa(10 to 15 minute/recording)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ERK phosphorylation	Distribution of variables and difference in the state of ERK phosphorylation in two contrasted groups : the dyskinetic levodopa-treated PD group and control group.	Day 1

Secondary Outcome Measures

Outcome Measure	Time Frame
plasma and urinary dopamine in "on" and "off" state	Day 1
measure derivatives of morphine	Day 1

Collaborators and Investigators

• Sponsor: University Hospital, Bordeaux
• Collaborators: Université Victor Segalen Bordeaux 2
• Investigators: Principal Investigator: Nathalie DAMON-PERRIERE, Dr., University Hospital, Bordeaux; Study Chair: Genevieve Chene, Pr, University Hospital, Bordeaux

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Actual): July 1, 2012
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: June 1, 2010
• First Submitted That Met QC Criteria: June 10, 2010
• First Posted (Estimate): June 11, 2010

Study Record Updates

• Last Update Posted (Estimate): July 31, 2012
• Last Update Submitted That Met QC Criteria: July 30, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: CHUBX 2009/20

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No