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In Vivo Noradrenergic System and Aging (NA2C-PET-MRI)

7 juillet 2026 mis à jour par: Hospices Civils de Lyon

Diving Into the in Vivo Noradrenergic System : Role of the alpha2C-adrenergic Receptors

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).

Aperçu de l'étude

Statut

Recrutement

Les conditions

Intervention / Traitement

Type d'étude

Interventionnel

Inscription (Estimé)

165

Phase

  • N'est pas applicable

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Coordonnées de l'étude

Sauvegarde des contacts de l'étude

Lieux d'étude

  • France
      • Bron, France, 69500
        • Recrutement
        • Hôpital Neurologique Pierre Wertheimer - Service de Neurologie
        • Contact:
        • Chercheur principal:
          • Chloé Laurencin, MD/PhD

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

  • Adulte
  • Adulte plus âgé

Accepte les volontaires sains

Oui

La description

Inclusion Criteria for the healthy controls:

  • Age between 20 years and 80 years
  • Weight between 40kg and 100kg
  • Without neurologic or psychiatric history
  • Without head trauma history including loss of consciousness superior to 30 minutes.
  • With highly effective contraception for women of childbearing age
  • Affiliated to a social security or similar scheme
  • Not subject to any legal protection measures
  • Participant must have signed an informed consent document

Inclusion Criteria for the patients with Parkinson's disease:

  • Age between 40 years and 80 years
  • Weight between 40kg and 100kg
  • With an idiopathic Parkinson's disease (Dopa-sensitive)
  • Without head trauma history including loss of consciousness superior to 30 minutes.
  • Without associated neurological pathology
  • With highly effective contraception for women of childbearing age
  • Affiliated to a social security or similar scheme
  • Not subject to any legal protection measures
  • Participant must have signed an informed consent document

Exclusion Criteria for all participants :

  • Subject receiving (or having received in the last month) somatic medication with cerebral or psychological effects (e.g., antihistamines), see list in Appendix1
  • Subjects with a current or past dependence on alcohol or any other addictive substance according to DSM-IV-TR criteria, with the exception of nicotine and caffeine; -
  • Subjects already participating in another biomedical research project or who have participated in a study using ionizing radiation within the past year;
  • Pregnant woman parturient or breastfeeding
  • MRI contraindications (: people using pacemaker or insulin pumps, with implanted or embedded metal objects in the head or body, claustrophobic, with neurosensory stimulators or implantable defibrillators, with cochlear implants, with ferromagnetic foreign bodies in the eye or brain close to nerve structures, agitation of the subject (uncooperative or agitated subjects), ventriculoperitoneal neurosurgical shunt valves, dental appliances)
  • Subject with a contraindication to PET scans at the ORM: hypersensitivity to the active substance or to any of the excipients (sodium chloride)
  • Subjects who are unable to understand or complete the study (language barrier, obvious lack of motivation, etc.) as judged by the investigator.
  • Subjects who do not agree to be informed in the event of an incidental finding of an abnormality on MRI or during neuropsychological assessment.
  • Persons deprived of their liberty by judicial or administrative decision.
  • Persons receiving psychiatric care.
  • Persons admitted to a health or social care facility for purposes other than research.

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Science basique
  • Répartition: Non randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Autre: Healthy controls
120 healthy participants (balanced for sex) ranging from 20 to 80 years old will be included.
Autre: PET/MRI scanning session
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.
Comportemental: Neuropsychological examination
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.
Comportemental: Olfactory screening
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.
Expérimental: Parkinson's disease
45 parkinsonian patients with an akineto-rigid phenotype will be included.
Autre: PET/MRI scanning session
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.
Comportemental: Neuropsychological examination
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.
Comportemental: Olfactory screening
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.

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
PET measures
Délai: Day 1
Derived from the PET data, the binding potential (BPND) parametric maps will be calculated using compartmental modelling techniques.
Day 1
IRM measure
Délai: Day 1
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

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Global Cognitive Assessment
Délai: Day 2
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
Délai: Day 2
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.
Day 2
Working memory Assessment
Délai: Day 2
Measured with the Digit Span Memory test. Outcome measure is the total number of items correctly repeated.
Day 2
Executive Functioning
Délai: Day 2
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
Délai: Day 2
Measured with the Tower of London test. Outcome measure is the total correct and total moves score.
Day 2
Verbal fluencies
Délai: Day 2
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
Délai: Day 2
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
Délai: Day 1
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
Délai: Day 1
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
Délai: Day 2
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
Délai: Day 2
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
Délai: Day 2
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
Délai: Day 1
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
Délai: Day 2
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
Délai: Day 2
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
Délai: Day 2
Measured by the UPPS Impulsive Behavior Scale. Outcome measure is between 0 and 80, higher score indicating severe impulsivity.
Day 2
Autonomic function
Délai: Day 2
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
Délai: Day 2
Outcome measure is between 0 and 16,higher score indicating better performance.
Day 2
Olfactory assessment: odor discrimination
Délai: Day 2
Outcome measure is between 0 and 16 with higher score indicating better performance.
Day 2
Olfactory assessment: odor identification
Délai: Day 2
Outcome measure is between 0 and 16 with higher score indicating better performance.
Day 2

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Hospices Civils de Lyon

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

29 juin 2026

Achèvement primaire (Estimé)

1 septembre 2029

Achèvement de l'étude (Estimé)

1 septembre 2029

Dates d'inscription aux études

Première soumission

28 avril 2026

Première soumission répondant aux critères de contrôle qualité

28 avril 2026

Première publication (Réel)

6 mai 2026

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

9 juillet 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

7 juillet 2026

Dernière vérification

1 juillet 2026

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • 69HCL24_1120
  • 2025-524602-15-00 (Ctis)

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Non

Étudie un produit d'appareil réglementé par la FDA américaine

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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