Synaptic Density and Progression of Parkinson's Disease.

Study Overview
=================
Brief Summary
-----------------
AIM: To assess synaptic density and to investigate the potential relationship of regional synaptic loss with motor and non-motor symptoms and with disease progression in the human brain in vivo in patients with PD. DESIGN: We will include 30 PD patients and 20 healthy controls. All subjects will undergo a clinical examination, with comprehensive assessment of motor and non-motor symptoms, and imaging evaluation consisting of 11C-UCB-J PET-CT and 18F-FE-PE2I PET-MR at baseline and after 2 years.

Official Title
-----------------
Longitudinal Measurement of Synaptic Density to Monitor Progression of Parkinson's Disease.

Conditions
-----------------
Parkinson Disease

Intervention / Treatment
-----------------
* Other: 11C-UCB-J PET-CT
* Other: 18F-PE2I PET-MR


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: PD diagnosis based on MDS clinical diagnostic criteria for Parkinson's disease Less than 5 years disease duration since motor symptom onset according to the patient Hoehn-Yahr stage 1 or 2 in medication ON state Capacity to understand the informed consent form Exclusion Criteria: Neuropsychiatric diseases other than PD Major internal medical diseases Relevant abnormalities on MR brain History of alcohol or drug abuse Contraindications for MR Pregnancy Previous participation in other research studies involving ionizing radiation with > 1 mSv over past 12 months.

Ages Eligible for Study
-----------------
Minimum Age: 30 Years
Maximum Age: 80 Years

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

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

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

Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: Longitudinal study design (2 years follow up) where results of SV2A PET/CT, PE2I PET/MR and clinical rating scales are compared between PD patients and healthy controls.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PD patients<br>At baseline and 2-year follow-up | Other: 11C-UCB-J PET-CT<br>* Positron Emission Tomography (PET) of synaptic vesicle protein 2A (SV2A) using the radioligand 11C-UCB-J.<br>Other: 18F-PE2I PET-MR<br>* Positron Emission Tomography (PET) of dopamine transporter (DAT) using the radioligand 18F-FE-PE2I, and brain MRI performed simultaneously.<br>|
| Active Comparator: Healthy controls<br>At baseline and 2-year follow-up | Other: 11C-UCB-J PET-CT<br>* Positron Emission Tomography (PET) of synaptic vesicle protein 2A (SV2A) using the radioligand 11C-UCB-J.<br>Other: 18F-PE2I PET-MR<br>* Positron Emission Tomography (PET) of dopamine transporter (DAT) using the radioligand 18F-FE-PE2I, and brain MRI performed simultaneously.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline differences in synaptic density. | Baseline differences (%) in synaptic density between patients and controls. | Data analysis wel be done when all subjects have undergone the baseline evaluation. | 
| Correlations between clinical scores and synaptic density. | Correlations between clinical scores and synaptic density in the patient group. | Data analysis wel be done when all subjects have undergone the 2-year follow-up evaluation. | 
| Differences in the rate of decline of synaptic density. | Differences (%) in the rate of decline of synaptic density between patients and controls. | Data analysis wel be done when all subjects have undergone the 2-year follow-up evaluation. | 
| Correlations between progression of the clinical scores and decline of synaptic density. | Correlations between progression of the clinical scores and decline of synaptic density in the patient group. | Data analysis wel be done when all subjects have undergone the 2-year follow-up evaluation. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline differences in DAT levels. | Baseline differences (%) in DAT levels between patients and controls. | Data analysis wel be done when all subjects have undergone the baseline evaluation. | 
| Correlations between clinical scores and DAT levels. | Correlations between clinical scores and DAT levels in the patient group. | Data analysis wel be done when all subjects have undergone the 2-year follow-up evaluation. | 
| Differences in the rate of decline of global and DAT levels. | Differences (%) in the rate of decline of global and DAT levels between patients and controls. | Data analysis wel be done when all subjects have undergone the 2-year follow-up evaluation. | 
| Correlations between progression of the clinical scores and decline of DAT levels. | Correlations between progression of the clinical scores and decline of DAT levels in the patient group. | Data analysis wel be done when all subjects have undergone the 2-year follow-up evaluation. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
PET, Parkinson Disease, UCB-J, PE2I