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| ID | Type | Description | Link |
|---|---|---|---|
| 2025-524602-15-00 | EU Trial (CTIS) Number |
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The main goal of this research proposal is to provide, for the first time in humans, a wider understanding of the role of the noradrenergic system both in health and illness (here Parkinson's disease) through the use of a newly developed radiotracer visualizing alpha2C-ARs ([11C]ORM-13070) combined with a cutting-edge technology, the hybrid PET/MRI scanner. The secondary aim will be to determine whether the expected age- and PD-related changes in the noradrenergic system are paralleled by changes in neuropsychological performances (i.e. cognitive, motor and/or olfactory abilities).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Healthy controls | Other | 120 healthy participants (balanced for sex) ranging from 20 to 80 years old will be included. |
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| Parkinson's disease | Experimental | 45 parkinsonian patients with an akineto-rigid phenotype will be included. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PET/MRI scanning session | Other | Each participant will undergo 45 min of PET/MRI recording that will begin immediately after an intravenous bolus injection of [11C]ORM-13070 (350 MBq ± 10%) and will last for 45 minutes in a resting state. During this time, MRI acquisition will include several MRI sequences: 1) One sagittal MP-RAGE sequence of high-resolution anatomical 3D T1-weighted images (5 min); 2) One 3D T2 FLAIR sequence (5 min); (3) One turbo spin-echo (TSE) neuromelanin-sensitive sequence (7 min, Garcia-Lorenzo et al., 2013); 3) One echo-planar imaging (EPI) sequence in the axial plane (15 min duration) to acquire diffusion images; and 4) One 13-min resting-state fMRI run using high resolution T2* weighted gradient-echo EPI sequences covering the entire brain and including the lower brainstem. |
| Measure | Description | Time Frame |
|---|---|---|
| PET measures | Derived from the PET data, the binding potential (BPND) parametric maps will be calculated using compartmental modelling techniques. | Day 1 |
| IRM measure | Derived from the MRI data, the LC will be defined with a semi-automatic method from the MRI sequence sensitive to neuromelanin, and its signal intensity will be calculated for each participant as previously described (Laurencin et al., 2024a) | Day 1 |
| Measure | Description | Time Frame |
|---|---|---|
| Global Cognitive Assessment | Measured with Montreal Cognitive Assessment. Outcome measure is between 0 and 30. A score of 26 or over is considered to be normal. | Day 2 |
| Memory Assessment | Measured with the 16-item Free and Cued Recall test. Outcome measure is the total immediate recall which is the sum of free and cued recall. |
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Inclusion Criteria for the healthy controls:
Inclusion Criteria for the patients with Parkinson's disease:
Exclusion Criteria for all participants :
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Chloé Laurencin, MD / PhD | Contact | 472118022 | +33 | chloe.laurencin@chu-lyon.fr |
| Bénédicte Ballanger, PhD | Contact | 472138978 | +33 | benedicte.ballanger@cnrs.fr |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hôpital Neurologique Pierre Wertheimer - Service de Neurologie | Recruiting | Bron | 69500 | France |
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| ID | Term |
|---|---|
| D010300 | Parkinson Disease |
| D001519 | Behavior |
| ID | Term |
|---|---|
| D020734 | Parkinsonian Disorders |
| D001480 | Basal Ganglia Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| ID | Term |
|---|---|
| D009483 | Neuropsychological Tests |
| ID | Term |
|---|---|
| D011581 | Psychological Tests |
| D004191 | Behavioral Disciplines and Activities |
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| Neuropsychological examination | Behavioral | A battery of neuropsychological tests will assess cognitive, emotional, and sensory domains linked to noradrenaline function. Participants will complete the Montreal Cognitive Assessment for global cognitive function, the Digit Span and Free Recall tests for memory, the Trail Making, Tower of London and Stroop tests for executive functioning, Beck Depression Inventory for mood, State-Trait Anxiety Inventory for anxiety, the Epworth and RBD screening questionnaire for sleep, the visual analog and Kings PD scales for pain, the Lille Apathy Rating Scale for apathy, the VOSP for visuo-spatial capacity, the PDFS-16 for fatigue, the UPPS for impulsivity, and the SCOPA-AUT for autonomic assessment. |
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| Olfactory screening | Behavioral | An olfactory screening (30-40 min) using the extended ODOFIN (BURGHART) Sniffin' Sticks Test battery (Burghart Messtechnik Denmark). This battery consists of 3 tests: The threshold (T) test has 48 Sniffin' Sticks (32 blanks and 16 dilutions with 2-Phenylethanol) and is used to ascertain the participant's olfactory threshold. The discrimination (D) test consists of 48 Sniffin' Sticks (16 triplets of odorants) where the participant must tell the odd one out in the triplet. The identification (I) test consists of 16 Sniffin' Sticks with everyday smells which the participant has to name using a selection card containing four choices. Together, these make up the TDI score. |
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| Day 2 |
| Working memory Assessment | Measured with the Digit Span Memory test. Outcome measure is the total number of items correctly repeated. | Day 2 |
| Executive Functioning | Measured with the Trail Making test. Unit of measure is first seconds to perform the test, which will be converted in a percentile score and then number of errors made during the test. | Day 2 |
| Planning Functioning | Measured with the Tower of London test. Outcome measure is the total correct and total moves score. | Day 2 |
| Verbal fluencies | Measured with both the category (semantic fluency) and letter (phonemic fluency) test. Outcome measure is the total number of words generated within 60 sec excluding repetitions | Day 2 |
| Visuo-spatial Assessment | Measured by the Visual Object and Space Perception Battery. The study will use a selection of theses tests : incomplete letters (outcome measure is between 0 and 20; cut-off score = 16) and number position discrimination (outcome measure is between 0 and 10; cut-off score = 7) | Day 2 |
| Depression Evaluation | Measured by the Beck Depression Inventory-II Questionnaire. Outcome measure is between 0 and 20 with a cut-off score = 13. A score higher than 14 indicates the presence of depression | Day 1 |
| Anxiety Evaluation | Measured by the State-Trait Anxiety Inventory (STAI) form Y questionnaire. Outcome measure is between 20 and 80, with higher scores correlating with greater anxiety | Day 1 |
| Day time sleepiness evaluation | Measured by the Epworth Sleepiness Scale Questionnaire. Outcome measure is between 0 and 24 with a score between 0-8 indicating normal Daytime sleepiness, a score between 9-14 indicating mild sleep deficiency and a score above 15 an excessive daytime sleepiness. | Day 2 |
| Sleep Quality | Measured by the Pittsburgh Sleep Quality Index (PSQI). Outcome measure is between 0 and 21 with 0 indicating no sleep problem and 21 major sleep disorder. | Day 2 |
| Rapid Eye Movement Behavior disorder | Measured by the RBDSQ. Outcome measure is between 0 and 10 with 0 indicating no RBD problem and 10 major RBD disorder. | Day 2 |
| Pain Assessment | Measured by the Visual Analog Pain Scale. Outcome measure is between 0 and 10 with 0 indicating no pain problem and a score higher than 7 an extreme pain. | Day 1 |
| Apathy Assessment | Measured by the Lille Apathy rating scale. Outcome measure is between -36 to 36 with -36 indicating absence of apathy and 36 severe apathy | Day 2 |
| Fatigue Assessment | Measured by the Parkinson's disease fatigue Scale (PDFS-16).Outcome measure is between 0 and 80,higher score indicating extreme fatigue. | Day 2 |
| Impulsivity assessment | Measured by the UPPS Impulsive Behavior Scale. Outcome measure is between 0 and 80, higher score indicating severe impulsivity. | Day 2 |
| Autonomic function | Measured by the Scales for Outcomes in Parkinson's disease (SCOPA-AUT). Outcome measure is between 0 and 69,higher score indicating presence of autonomic dysfunctions. | Day 2 |
| Olfactory assessment: odor threshold | Outcome measure is between 0 and 16,higher score indicating better performance. | Day 2 |
| Olfactory assessment: odor discrimination | Outcome measure is between 0 and 16 with higher score indicating better performance. | Day 2 |
| Olfactory assessment: odor identification | Outcome measure is between 0 and 16 with higher score indicating better performance. | Day 2 |
| D009422 | Nervous System Diseases |
| D009069 | Movement Disorders |
| D000080874 | Synucleinopathies |
| D019636 | Neurodegenerative Diseases |