Human Aging and in Vivo Noradrenergic System (NA_PET_MRI)

Investigating the Noradrenergic System in the Living Human Brain With Hybrid Molecular Functional Imaging

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 (Parkinson's disease) through the use of a newly developed radiotracer (11Carbon [11C]Yohimbine) visualizing alpha-2 (α2) adrenergic receptors (AR) combined with cutting-edge technology, the hybrid positron emission tomography (PET)/magnetic resonance imaging (MRI) scanner. The secondary aim of this study will be to determine whether the expected age- and Parkinson's disease (PD)-related changes in the noradrenergic system are paralleled by changes in neuropsychological performances (such as cognitive, motor and/or olfactory abilities).

Study Overview

• Status: Unknown
• Conditions: Parkinson Disease
• Intervention / Treatment: Other: The role of the noradrenergic system across the life span (Healthy Subjects); Other: The role of the noradrenergic system across the life span (Parkinson's Disease Subjects)

• Study Type: Interventional
• Enrollment (Anticipated): 135
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Chloé Laurencin, MD; Phone Number: 33 4.72.11.80.22; Email: chloe.laurencin@chu-lyon.fr
• Study Contact Backup: Name: Bénédicte BALLANGER; Phone Number: 06.87.90.11.01; Email: benedicte.ballanger@cnrs.fr

Study Locations

• France
  • Bron, France
    • Recruiting
    • Hôpital Neurologique Pierre Wertheimer, Groupement Hospitalier Est
    • Contact: Bénédicte BALLANGER; Phone Number: 06.87.90.11.01; Email: benedicte.ballanger@cnrs.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria for the healthy controls:

• Age between 20 years and 80 years
• Weight between 40 kilograms (kg) and 95kg
• Without neurologic or psychiatric history
• Without head trauma history including loss of consciousness superior to 30 minutes.
• Affiliated to a social security or similar scheme
• Not subject to any legal protection measures
• Participant must have signed an informed consent document indicating that they understand the purpose of, and procedures required for, the study and are willing to participate in the study and comply with the study procedures and restrictions

Inclusion Criteria for the patients with Parkinson's disease:

• Age between 40 and 80 years old
• Weight between 40 kilograms (kg) and 95kg
• With an idiopathic Parkinson's disease (Dopa-sensitive)
• Without head trauma history including loss of consciousness superior to 30 minutes.
• Affiliated to a social security or similar scheme
• Not subject to any legal protection measures
• Participant must have signed an informed consent document indicating that they understand the purpose of, and procedures required for, the study and are willing to participate in the study and comply with the study procedures and restrictions

Exclusion Criteria:

• Subject with alcohol or substance abuse history
• Subject with somatic drug therapies
• Magnetic Resonance Imaging (MRI) contraindications (implanted or embedded metal objects in the head or body)
• Positron Emission Tomography (PET) contraindications
• Exposed to 1 millisievert or more of ionizing radiation in the year before the start of this study
• Subject unable to sign written consent for participation in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Healthy controls	Other: The role of the noradrenergic system across the life span (Healthy Subjects); A sample (n=90) of balanced distribution of healthy males and females within a continuous segment of the adult life span from 20 to 80 years old will be recruited, with approximately 7 males and 7 females subjects for each decade of age. Each participant will undergo 1) a neuropsychological examination, 2) an olfactory screening and 3) a 90 min 11C-Yohimbine positron emission tomography (PET)/magnetic resonance imaging (MRI) scan in a resting state.
EXPERIMENTAL: Parkinson disease	Other: The role of the noradrenergic system across the life span (Parkinson's Disease Subjects); Three groups of Parkinson Disease (PD) patients (each of them n=15) will be studied according to the duration and stage of the disease: early stage (the same group in Task 2); mid stage (5-7 years of disease duration; Hoehn and Yahr in Off 2-3); late stage (7-10 years of disease duration; Hoehn and Yahr in Off 3-4).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI) measures	Derived from the Positron Emission Tomography (PET) data, the binding potentials will be calculated using compartmental modelling techniques. Derived from the Magnetic Resonance Imaging (MRI) data.	Day 1 -180 minutes

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 - 10 minutes
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 - 20 minutes
Working Memory Assessment	Measured with the Digit Span Memory test. Outcome measure is the total number of items correctly repeated.	Day 2 - 20 minutes
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 - 20 minutes
Planning Functioning	Measured with the Tower of London test. Outcome measure is the total correct and total moves score.	Day 2 - 20 minutes
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 position discrimination (outcome measure is between 0 and 10; cut-off score = 7)	Day 2 - 20 minutes
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 2 - 10 minutes
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 2 - 10 minutes
Praxic Abilities	Measured by the Mahieux Praxic test. Outcome measure is between 0 and 23.	Day 2 - 10 minutes
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 - 5 minutes
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 - 5 minutes
Olfactory assessment : odor detection	The odor detection capability will be evaluated using a phenyl-ethyl alcohol (PEA) test. In this experiment, the detection threshold is obtained using a "staircase" procedure. Outcome measure is between 0 and 16 with higher score indicating better performance.	Day 2 - 30 minutes
Olfactory assessment: odor discrimination	Odor discrimination capacity will be assessed by asking the participant to smell three bottles (two bottles contain the same odor, and the third contains a different smell). The test includes 16 triplets of odorous substances. Outcome measure is between 0 and 16 with higher score indicating better performance.	Day 2 - 30 minutes
Olfactory assessment : odor identification	The odor identification capacity will be estimated by the European test of olfactory capacities (ETOC), a test based on 16 identifications. Outcome measure is between 0 and 16 with higher score indicating better performance.	Day 2 - 30 minutes

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon
• Investigators: Principal Investigator: Chloé Laurencin, MD, Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 29, 2019
• Primary Completion (ANTICIPATED): June 29, 2021
• Study Completion (ANTICIPATED): June 29, 2021

Study Registration Dates

• First Submitted: April 11, 2019
• First Submitted That Met QC Criteria: May 6, 2019
• First Posted (ACTUAL): May 8, 2019

Study Record Updates

• Last Update Posted (ACTUAL): June 24, 2019
• Last Update Submitted That Met QC Criteria: June 21, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: Positron Emission Tomography; Behavior; Magnetic Resonance Imaging; Aging; Human; Noradrenergic system
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Sympathomimetics; Vasoconstrictor Agents; Norepinephrine
• Other Study ID Numbers: 69HCL18_0409; 2018-003999-13 (EUDRACT_NUMBER)

Drug and device information, study documents

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