Clinical trial NCT01142739: Phosphorylation of ERK1/2 in Patients With Parkinson's Disease
Official title: A Descriptive Study of Lymphocytic Phosphorylation of ERK1/2 in Patients With Parkinson's Disease With Dyskinesias and in Controls
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Parkinson Disease
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
Collaborators: name: Université Victor Segalen Bordeaux 2
First posted: 2010-06-11
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
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.

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: ERK phosphorylation
timeFrame: Day 1
Secondary outcomes:
measure: plasma and urinary dopamine in "on" and "off" state
timeFrame: Day 1
measure: measure derivatives of morphine
timeFrame: Day 1
Other outcomes:
Locations:
city: Pessac
country: France
facility: CHU de Bordeaux Hôpital Haut Lévêque
Study officials:
affiliation: University Hospital, Bordeaux
name: Nathalie DAMON-PERRIERE, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital, Bordeaux
name: Geneviève CHENE, Pr
role: STUDY_CHAIR
References: