[11C]Yohimbine PET Study of alpha2-AR ([11C]Yohimbine)

Positron Emission Tomography Study of alpha2-adrenergic Receptors With [11C]Yohimbine

The main purpose of this study is to model tissue specific kinetics of [11C]Yohimbine in healthy male participants by positron emission tomography (PET) and the appropriate arterial input function (part A) ; to determine the reproducibility of measures (classical test-retest study, part B1) and to measure the blocking of [11C]Yohimbine uptake in the brain following single oral dose administration of clonidine (part B2).

Study Overview

• Status: Completed
• Conditions: Healthy Controls
• Intervention / Treatment: Drug: [11C]Yohimbine; Drug: [11C]Yohimbine (Part B1) and [11C]Yohimbine + clonidine (Part B2)

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Bron, France, 69500
    • Service de Neurologie C - Hôpital Neurologique et Neurochirurgical Pierre Wertheimer, GHE

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 35 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy male volunteers
• Age between 20 years and 35 years
• Weight between 50kg and 90kg
• 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

Exclusion Criteria:

• Allen test (assessing the arterial blood flow to the hand) indicating abnormal blood supply to the hand
• Subject with orthostatic hypotension
• Subject with alcohol or substance abuses history
• Subject with somatic drug therapies
• MRI contraindications (implanted or embedded metal objects in the head or body)
• PET contraindications
• Clonidine 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: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A : Imput function; Compartmental model of the volume of distribution of [11C]Yohimbine in Brain by PET	Drug: [11C]Yohimbine; Each subject will receive an intravenous (IV) bolus injection of [11C]Yohimbine at a dose of 370 MegaBecquerel (MBq) ± 10% with concomitant arterial blood sampling. The distribution of [11C]Yohimbine in brain will be measured by dynamic PET scans obtained from the time of injection for up to 90 minutes along with measurement of the tracer input function with arterial samples for intact tracer and metabolites to establish the total and regional compartmental kinetics of [11C]Yohimbine.
Experimental: Part B : validity of the measure; Part B1 : Test Retest Variability in the distribution of [11C]Yohimbine Part B2 : Percentage of alpha2-adrenergic receptor occupancy	Drug: [11C]Yohimbine (Part B1) and [11C]Yohimbine + clonidine (Part B2); Part B1 : Test Retest Variability will be assessed on percent difference in the binding potential following [11C]Yohimbine PET scan (IV bolus injection of [11C]Yohimbine at a dose of 370 MBq ± 10%) obtained at least 1 week after [11C]Yohimbine PET scan of part A. Part B2 : Occupancy of alpha2-adrenergic receptors in brain by clonidine will be evaluated by comparing the binding potential of [11C]Yohimbine (IV bolus injection of [11C]Yohimbine at a dose of 370 MBq ± 10%) after single oral dose of clonidine (0,15mg) to the binding potential of [11C]Yohimbine obtained at baseline (part A).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Binding potentials	Binding potentials are calculated using compartmental modelling techniques	180 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events as a measure of safety and tolerability	An adverse effect is any untoward medical events that occur in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product	Up to 7 days after part B

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon
• Investigators: Principal Investigator: Chloe LAURENCIN, MD, Service de neurologie C

Study record dates

Study Major Dates

• Study Start (Actual): May 21, 2018
• Primary Completion (Actual): July 21, 2018
• Study Completion (Actual): January 21, 2019

Study Registration Dates

• First Submitted: April 26, 2018
• First Submitted That Met QC Criteria: May 8, 2018
• First Posted (Actual): May 9, 2018

Study Record Updates

• Last Update Posted (Actual): February 6, 2020
• Last Update Submitted That Met QC Criteria: February 4, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: PET imaging; Radiotracer; Noradrenaline
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Autonomic Agents; Peripheral Nervous System Agents; Urological Agents; Analgesics; Sensory System Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Sympatholytics; Adrenergic alpha-Antagonists; Mydriatics; Adrenergic alpha-2 Receptor Antagonists; Clonidine; Yohimbine
• Other Study ID Numbers: 69HCL17_0196; 2018-000380-82 (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