PET Imaging of Cannabinoid CB1 Receptors Using [18F]FMPEP-d2

This study has been completed.

Sponsor:

Information provided by:

National Institutes of Health Clinical Center (CC)

ClinicalTrials.gov Identifier:

NCT00598286

First received: January 10, 2008

Last updated: May 9, 2012

Last verified: May 2012

History of Changes

Tracking Information
First Received Date ^ICMJE	January 10, 2008
Last Updated Date	May 9, 2012
Start Date ^ICMJE	January 2008
Primary Completion Date	October 2009 (final data collection date for primary outcome measure)
Current Primary Outcome Measures ^ICMJE (submitted: March 27, 2008)	Efficacy of novel PET tracer for CB1 in brain imaging.
Original Primary Outcome Measures ^ICMJE (submitted: January 10, 2008)	Efficacy of novel PET tracer for CB1 in brain imaging
Change History	Complete list of historical versions of study NCT00598286 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ^ICMJE (submitted: March 27, 2008)	Distribution and variance of CB1 receptors in the brain of healthy controls.
Original Secondary Outcome Measures ^ICMJE (submitted: January 10, 2008)	Distribution and variance of CB1 receptors in the brain of healthy controls
Current Other Outcome Measures ^ICMJE	Not Provided
Original Other Outcome Measures ^ICMJE	Not Provided

Descriptive Information
Brief Title ^ICMJE	PET Imaging of Cannabinoid CB1 Receptors Using [18F]FMPEP-d2
Official Title ^ICMJE	Imaging of Cannabinoid CB1 Receptors Using [18F]FMPEP-d2
Brief Summary	The purpose of this protocol is to measure brain CB1 receptors in the hope to better understand how they work, so that one day we can understand how the CB1 receptors are involved in psychiatric, neurological, and behavioral disorders.
Detailed Description	BRAIN IMAGING Objective The central cannabinoid receptor (CB1) is one of the most abundant neuromodulatory receptors in the brain. It is found on glutamatergic, dopaminergic and GABA-ergic synaptic terminals and belongs to G-protein coupled receptor family. The CB1 is a target for drug therapy, including the use of an antagonist as an appetite suppressant. The central cannabinoid receptor CB1 has never been visualized in humans. In collaboration with Eli Lilly, we developed a promising PET ligand for the CB1 receptor: [18F]FMPEP-d2 ((3R,5R)-5-(3-(fluoromethoxy)phenyl)-3-((R)-1-phenylethylamino)-1-(4-(trifluoromethyl)phenyl)pyrrolidin-2-one). Study Population In the current protocol, we wish to evaluate [18F]FMPEP-d2 in approximately 10 healthy subjects. Design Brain imaging studies will consist of subject evaluation followed by PET and MRI scans. Outcome Measures We intend to determine the kinetics of brain uptake and washout, clearance in the plasma, and the distribution volume of [18F]FMPEP-d2 calculated with compartmental modeling. Distribution volume is proportional to the density of receptors and is equal to the ratio at equilibrium of uptake in brain to the concentration of parent radiotracer in plasma. WHOLE BODY DOSIMETRY Objective Should the brain imaging studies prove to be successful, we will continue with whole body dosimetry studies. Preliminary dosimetry studies with [18F]d2-FMPEP have been performed in nonhuman primates; however, these need to be continued in humans before further investigation of this novel tracer can continue. Study Population In the current protocol, we wish to evaluate [18F]FMPEP-d2 in approximately 10 additional healthy subjects. Design The whole body dosimetry studies will consist of subject evaluation followed by a PET scan. Outcome Measures We intend to determine the whole body distribution of activity and thereby calculate radiation exposure to organs of the body. BRAIN IMAGING WITH TEST/RE-TEST Objective Should the brain imaging and dosimetry studies prove to be successful, we will continue with test/retest brain imaging studies. Test/retest studies with [18F]FMPEP-d2 will provide evidence of reproducibility and strengthen the assurance that this radioligand can be used to assess pathology. Previous investigations in developing a CB1 receptor PET tracer have demonstrated the need to test reproducibility (Terry, In Writing; Burns et al 2007). Study Population In the current protocol, we wish to evaluate [18F]FMPEP-d2 in approximately 10 additional healthy subjects. Design The brain imaging test/retest studies will consist of subject evaluation followed by one MRI and two PET scans. Outcome Measures We intend to determine the reproducibility of the outcome measures from the brain imaging, namely, distribution volume.
Study Type ^ICMJE	Interventional
Study Phase	Phase 1
Study Design ^ICMJE	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Diagnostic
Condition ^ICMJE	CB1 Cannabinoid PET [18F]FMPEP-d2 Brain Imaging
Intervention ^ICMJE	Drug: [18F]FMPEP-d2 N/A
Study Arm (s)	Not Provided
Publications *	Abi-Dargham A, Gandelman M, Zoghbi SS, Laruelle M, Baldwin RM, Randall P, Zea-Ponce Y, Charney DS, Hoffer PB, Innis RB. Reproducibility of SPECT measurement of benzodiazepine receptors in human brain with iodine-123-iomazenil. J Nucl Med. 1995 Feb;36(2):167-75. Burger C, Buck A. Requirements and implementation of a flexible kinetic modeling tool. J Nucl Med. 1997 Nov;38(11):1818-23. Burns HD, Van Laere K, Sanabria-Bohórquez S, Hamill TG, Bormans G, Eng WS, Gibson R, Ryan C, Connolly B, Patel S, Krause S, Vanko A, Van Hecken A, Dupont P, De Lepeleire I, Rothenberg P, Stoch SA, Cote J, Hagmann WK, Jewell JP, Lin LS, Liu P, Goulet MT, Gottesdiener K, Wagner JA, de Hoon J, Mortelmans L, Fong TM, Hargreaves RJ. [18F]MK-9470, a positron emission tomography (PET) tracer for in vivo human PET brain imaging of the cannabinoid-1 receptor. Proc Natl Acad Sci U S A. 2007 Jun 5;104(23):9800-5. Epub 2007 May 29.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information
Recruitment Status ^ICMJE	Completed
Enrollment ^ICMJE	18
Completion Date	October 2009
Primary Completion Date	October 2009 (final data collection date for primary outcome measure)
Eligibility Criteria ^ICMJE	INCLUSION CRITERIA: All subjects must be healthy and aged 18-65 years, with history/physical exam, ECG, and laboratory tests within one year of the PET scan. The volunteer must sign an informed consent form. EXCLUSION CRITERIA: Current psychiatric illness, substance abuse including marijuana use, or severe systemic disease based on history and physical exam. Laboratory tests with clinically significant abnormalities or positive urine toxicology screen. Prior participation in other research protocols in the last year such that radiation exposure would exceed the annual limits. Pregnancy and breast feeding. Claustrophobia. Presence of ferromagnetic metal in the body or heart pacemaker. Positive HIV test. Employee of the investigative site or an immediate family member of an employee of the investigative site. Immediate family member is defined as a spouse, parent, child, or sibling, whether biological or legally adopted. Employee of Eli Lilly and Company.
Gender	Both
Ages	18 Years to 65 Years
Accepts Healthy Volunteers	Yes
Contacts ^ICMJE	Contact information is only displayed when the study is recruiting subjects
Location Countries ^ICMJE	United States

Administrative Information
NCT Number ^ICMJE	NCT00598286
Other Study ID Numbers ^ICMJE	080049, 08-M-0049
Has Data Monitoring Committee	Not Provided
Responsible Party	Robert B. Innis, M.D./National Institute of Mental Health, National Institutes of Health
Study Sponsor ^ICMJE	National Institute of Mental Health (NIMH)
Collaborators ^ICMJE	Not Provided
Investigators ^ICMJE	Not Provided
Information Provided By	National Institutes of Health Clinical Center (CC)
Verification Date	May 2012
^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

To Top