Human Aging and in Vivo Noradrenergic System (NA_PET_MRI)

• ClinicalTrials.gov Identifier: NCT03942289
• Recruitment Status: Unknown
• First Posted: May 8, 2019
• Last Update Posted: June 24, 2019
• Sponsor: Hospices Civils de Lyon
• Information provided by (Responsible Party): Hospices Civils de Lyon

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Parkinson Disease	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)	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 135 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Investigating the Noradrenergic System in the Living Human Brain With Hybrid Molecular Functional Imaging
• Actual Study Start Date: April 29, 2019
• Estimated Primary Completion Date: June 29, 2021
• Estimated Study Completion Date: June 29, 2021

Arms and Interventions

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).

Outcome Measures

Primary Outcome Measures :

1. Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI) measures [ Time Frame: Day 1 -180 minutes ]
   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.

Secondary Outcome Measures :

1. Global Cognitive Assessment [ Time Frame: Day 2 - 10 minutes ]
   Measured with Montreal Cognitive Assessment. Outcome measure is between 0 and 30. A score of 26 or over is considered to be normal.
2. Memory Assessment [ Time Frame: Day 2 - 20 minutes ]
   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.
3. Working Memory Assessment [ Time Frame: Day 2 - 20 minutes ]
   Measured with the Digit Span Memory test. Outcome measure is the total number of items correctly repeated.
4. Executive Functioning [ Time Frame: Day 2 - 20 minutes ]
   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.
5. Planning Functioning [ Time Frame: Day 2 - 20 minutes ]
   Measured with the Tower of London test. Outcome measure is the total correct and total moves score.
6. Visuo-spatial Assessment [ Time Frame: Day 2 - 20 minutes ]
   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)
7. Depression Evaluation [ Time Frame: Day 2 - 10 minutes ]
   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.
8. Anxiety Evaluation [ Time Frame: Day 2 - 10 minutes ]
   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.
9. Praxic Abilities [ Time Frame: Day 2 - 10 minutes ]
   Measured by the Mahieux Praxic test. Outcome measure is between 0 and 23.
10. Day time sleepiness evaluation [ Time Frame: Day 2 - 5 minutes ]
    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.
11. Sleep Quality [ Time Frame: Day 2 - 5 minutes ]
    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.
12. Olfactory assessment : odor detection [ Time Frame: Day 2 - 30 minutes ]
    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.
13. Olfactory assessment: odor discrimination [ Time Frame: Day 2 - 30 minutes ]
    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.
14. Olfactory assessment : odor identification [ Time Frame: Day 2 - 30 minutes ]
    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.

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Contacts

Contact: Chloé Laurencin, MD; 4.72.11.80.22 ext 33; chloe.laurencin@chu-lyon.fr

Contact: Bénédicte BALLANGER; 06.87.90.11.01; benedicte.ballanger@cnrs.fr

Locations

France

Hôpital Neurologique Pierre Wertheimer, Groupement Hospitalier Est; Recruiting

Bron, France

Contact: Bénédicte BALLANGER 06.87.90.11.01 benedicte.ballanger@cnrs.fr

Sponsors and Collaborators

Hospices Civils de Lyon

Investigators

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

More Information

• Responsible Party: Hospices Civils de Lyon
• ClinicalTrials.gov Identifier: NCT03942289
• Other Study ID Numbers: 69HCL18_0409; 2018-003999-13 ( EudraCT Number )
• First Posted: May 8, 2019
• Last Update Posted: June 24, 2019
• Last Verified: June 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Hospices Civils de Lyon:

Human; Aging; Behavior; Noradrenergic system; Positron Emission Tomography; Magnetic Resonance Imaging

Additional relevant MeSH terms:

Parkinson Disease; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Norepinephrine; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Sympathomimetics; Autonomic Agents; Peripheral Nervous System Agents; Vasoconstrictor Agents