Compensatory Mechanisms in Parkinson Disease (PD)

Study Overview
=================
Brief Summary
-----------------
Parkinson's disease is characterized by a large number of non motor, especially neuropsychiatric, signs. Their pathophysiology is complex but the role of dopaminergic and serotoninergic systems dysfunction is suggested by several studies. In addition, the serotoninergic system is involved in the pathophysiology of dyskinesias. Very few studies have analyzed the abnormalities of these two neurotransmission systems at disease onset, in de novo PD patients. Furthermore, the parallel evolution of the degeneration of the dopaminergic and serotoninergic systems with disease progression remains unknown. Thus the present study aims at determining, by using PET and 11C-PE2I and 11C-DASB the respective role of the serotoninergic and dopaminergic systems dysfunction in motor and non motor manifestations in PD, at different evolution stages.

Official Title
-----------------
Pathophysiology of Non Motor Signs and Compensatory Mechanisms in Parkinson's Disease: Role of the Serotoninergic and Dopaminergic Lesions Studied by PET

Conditions
-----------------
Parkinson's Disease

Intervention / Treatment
-----------------
* Device: PET


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients Patients presenting doparesponsive Parkinson's disease Patient's age between 40 and 70 years old Absence of other neurological or psychiatric disease Absence of cognitive decline ( MATTIS > 130) For women of childbearing age a pregnancy test and a contraceptive method will be required Informed consent sign Healthy subjects subject's age between 40 and 70 years old Absence of neurological or psychiatric disease Absence of cognitive decline ( MATTIS > 130) For women of childbearing age a pregnancy test and a contraceptive method will be required Informed consent sign Exclusion Criteria: Patients patient's age < 40 years old or > 70 years old Other neurological or psychiatric disease Cognitive decline (MATTIS < 130). Having participated to a PET or SPECT study in the last 12 months Pregnancy Severe concomitant disease Healthy subjects subject's age < 40 years old or > 70 years old Neurological or psychiatric disease Cognitive decline (MATTIS < 130). Having participated to a PET or SPECT study in the last 12 months Pregnancy Severe concomitant disease

Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PET<br> | Device: PET<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Respective progression of both dopaminergic and serotoninergic lesions in Parkinson's disease | Dopaminergic lesions will be determined by positron emission tomography (PET) using 11C-PE2I in 3 groups of PD patients (de novo; mid-stage (4-7 years of evolution); late-stage (8-10 years of evolution). Serotoninergic lesions will be assessed by positron emission tomography (PET) using 11C-DASB in the same 3 groups of PD patients. In addition a control group will be included. | This will be achieved at the end of the inclusion period, thus 24 to 36 months after study onset (January 2014). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlations between neuropsychiatric observed in Parkinson's disease at different stages of evolution | Dopaminergic lesions will be determined by positron emission tomography (PET) using 11C-PE2I in 3 groups of PD patients (de novo; mid-stage (4-7 years of evolution); late-stage (8-10 years of evolution). Serotoninergic lesions will be assessed by positron emission tomography (PET) using 11C-DASB in the same 3 groups of PD patients. In addition a control group will be included. The neuropsychiatric manifestations studied are : hypo and hyperdopaminergic signs : ECMP scale Apathy using LARS scale Anxiety using BAI scale Depression using BDI scale (Beck Depression Inventory) Affective well-being and asthenia using visual analogic scales of Norris MATHYS scale Global cognitive scale : MATTIS Food behavior using TFEQ scale Personality : TCI-R scale Impulsivity by UPPS scale | These correlations will be determined at the end of the inclusion period, thus 24 to 36 months after study onset (January 2014). | 
| Role of dopaminergic and serotoninergic lesions in fatigue | : Dopaminergic lesions will be determined by positron emission tomography (PET) using 11C-PE2I in 3 groups of PD patients (de novo; mid-stage (4-7 years of evolution); late-stage (8-10 years of evolution). Serotoninergic lesions will be assessed by positron emission tomography (PET) using 11C-DASB in the same 3 groups of PD patients. In addition a control group will be included. Fatigue will be assessed using the PDFS-16 scale | This will be determined at the end of the inclusion period, thus 24 to 36 months after study onset (January 2014). | 
| Relationship between the severity of dopaminergic and serotoninergic lesions and the quality of life | Dopaminergic lesions will be determined by positron emission tomography (PET) using 11C-PE2I in 3 groups of PD patients (de novo; mid-stage (4-7 years of evolution); late-stage (8-10 years of evolution). Serotoninergic lesions will be assessed by positron emission tomography (PET) using 11C-DASB in the same 3 groups of PD patients. In addition a control group will be included. Fatigue will be assessed using the PDQ39 (Parkinson's Disease Questionnaire) scale | These correlations will be determined at the end of the inclusion period, thus 24 to 36 months after study onset (January 2014). | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Parkinson, serotonin, dopamine, non motor, progression, PET