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

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).

Study Overview

• Status: Not yet recruiting
• Conditions: Healthy Aging and Parkinson's Disease
• Intervention / Treatment: Other: PET/MRI scanning session; Behavioral: Neuropsychological examination; Behavioral: Olfactory screening

• Study Type: Interventional
• Enrollment (Estimated): 165
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Chloé Laurencin, MD / PhD; Phone Number: +33 472118022; Email: chloe.laurencin@chu-lyon.fr
• Study Contact Backup: Name: Bénédicte Ballanger, PhD; Phone Number: +33 472138978; Email: benedicte.ballanger@cnrs.fr

Study Locations

• France
  • Bron, France, 69500
    • Hôpital Neurologique Pierre Wertheimer - Service de Neurologie
    • Contact: Chloé Laurencin, MD, PhD; Phone Number: +33 472118022; Email: chloe.laurencin@chu-lyon.fr
    • Principal Investigator: Chloé Laurencin, MD/PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Healthy controls; 120 healthy participants (balanced for sex) ranging from 20 to 80 years old will be included.	Other: 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.; Behavioral: 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.; Behavioral: 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.
Experimental: Parkinson's disease; 45 parkinsonian patients with an akineto-rigid phenotype will be included.	Other: 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.; Behavioral: 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.; Behavioral: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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.	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

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): October 1, 2029
• Study Completion (Estimated): October 1, 2029

Study Registration Dates

• First Submitted: April 28, 2026
• First Submitted That Met QC Criteria: April 28, 2026
• First Posted (Actual): May 6, 2026

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: MRI; PET; Behavior; Aging; Parkinson's disease; Noradrenaline; Locus Coeruleus; alpha2C
• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Parkinson Disease; Behavior; Behavioral Disciplines and Activities; Psychological Tests; Neuropsychological Tests
• Other Study ID Numbers: 69HCL24_1120; 2025-524602-15-00 (Ctis)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No