Exploratory Study of the Expression of the Serotonergic 5-HT4 Receptor in Parkinson's Disease

Study Overview
=================
Brief Summary
-----------------
The research aim to study in detail the motor, cognitive and affective modifications of Parkinsonian patients (compared to control subjects) at a moderate stage of the disease and to analyze by positron emission tomography (PET) imaging with the specific radioligand [11C]SB207145 the expression levels of this 5-HT4 receptor. At the same time, the study will monitor the impact of the 5-HTTLPR polymorphisms of Serotonin Transporter (SERT) and Brain-derived neurotrophic factor (BDNF) Val66Met on the expression of the 5-HT4 receptor in subjects.

Official Title
-----------------
Exploratory Study of the Expression of the Serotonergic 5-HT4 Receptor in Parkinson's

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

Intervention / Treatment
-----------------
* Other: neuropsychological assessment
* Other: biological sample
* Procedure: medical imagery


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Man or woman : Age between ≥ 50 and ≤ 85 years old For women: postmenopausal Affiliated to a social security scheme or similar; Having given written consent to participate in the free and informed study. Level of study: ≥ 6 years of schooling only for healthy volunteer : No history of neurological or psychiatric disease Only for patient : Having a clinically established or probable diagnosis of Parkinson's disease according to the criteria defined by the Movement Disorder Society at a Hoehn and Yahr stage ≤ 3 (in on dopa conditions) and a duration of evolution of the disease between 2 and 8 years. Only for patient : Having a MoCA (Montreal Cognitive Assessment) ≥ 20/30. Exclusion Criteria: Diagnosis other than Parkinson's disease ( for patient only) Treated with specific serotonin inhibitors (SSRIs), specific noradrenaline inhibitors (SNRIs), tricyclic antidepressants, monoamine oxidase inhibitors (MAOIs) and neuroleptics in the last 3 months Use of recreational drugs interfering with the serotonergic system (ecstasy, MDMA) or opioids (cannabis, opiates) in the last 3 months or chronic use Contraindication to magnetic resonance imaging (MRI) or positron emission tomography (PET) Participation in the last year to a study using ionizing radiation or concomitant participation in another research project involving the human being that may interfere with the results or the conclusions of this study Exceeding the annual amount of compensation authorized for participation in research protocols Deprivation of liberty by judicial or administrative decision, person subject to a legal protection measure BMI ≥ 35kg/m2 Presence of depression (BDI-2 score ≥21), anxiety (Parkinson Anxiety Scale (PAS) score ≥14) or apathy (STARKSTEIN score ≥14) - (for healthy volunteers only) Cognitive impairment (MOCA score ≤26) (for healthy volunteers only) Current or past neurological or psychiatric pathology (for healthy volunteers only) Serious and progressive medical pathology Current or past dependence on any addictive substance according to DSM-V (The Diagnostic and Statistical Manual of Mental Disorders) criteria (alcohol, cannabis, hallucinogens, inhalants, opiates, sedatives, stimulants), except tobacco and caffeine. (for healthy volunteers only)

Ages Eligible for Study
-----------------
Minimum Age: 50 Years
Maximum Age: 85 Years

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

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

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

Design Details

Primary Purpose: Health Services Research
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pet scan with the specific radioligand [11C]SB207145<br>The following examen are added by the study : neuropsychologic consultation PET scan MRI biological sample Questionnaires | Other: neuropsychological assessment<br>* a consultation to assess cognitive and psycho-behavioral functions with questionnaires<br>Other: biological sample<br>* 10 mL intravenous whole blood collection in EDTA tube<br>Procedure: medical imagery<br>* Pet scan with the specific radioligand [11C]SB207145 and MRI<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of the expression of the 5-HT4 receptor between patients with mild to moderate Parkinson's disease to age-matched healthy controls | difference in the tracer [11C]SB207145 's binding, the specific binding of the tracer will be calculated for each voxel with respect to a reference zone (the white matter of the cerebellum). | During MRI procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Description of 5-HT4 alterations related to motor symptoms | Relationship between the level of expression of the tracer and the clinical scores on the motor questionnaires | During MRI procedure | 
| Description of 5-HT4 alterations related to non-motor symptoms | Relationship between the level of expression of the tracer and the clinical scores on the non-motor questionnaires | During MRI procedure | 
| Description of 5-HT4 alterations related to cognitive symptoms | Relationship between the level of expression of the tracer and the clinical scores on the cognitive questionnaires | During MRI procedure | 
| Description of 5-HT4 alterations related to psychobehavioral symptoms | Relationship between the level of expression of the tracer and the clinical scores on the psychobehavioral questionnaires | During MRI procedure | 
| Description of 5-HT4 alterations related to SERT polymorphism data | Relationship between the level of expression of the tracer and SERT polymorphism data (5-HTTLPR polymorphism, evaluated as presence/absence) | During MRI procedure | 
| Description of 5-HT4 alterations related to BDNF polymorphism data | Relationship between the level of expression of the tracer and BDNF polymorphism data (Val66Met rs6265 polymorphism, evaluated as presence/absence) | During MRI procedure | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
serotonergic 5-HT4 receptor, radiotracer