PET Whole Body Biodistribution and Test Retest Bain Imaging Studies Using a Phosphodiesterase 4 Inhibitor (R)-[11C]Rolipram - Full Text View

Sponsored by:	National Institute of Mental Health (NIMH)
Information provided by:	National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:	NCT00250172

Purpose

The purpose of this study is to measure a particular protein in the brain called the phosphodiesterase by using the imaging techniques of positron emission tomography (PET) and magnetic resonance imaging (MRI).

Condition	Intervention	Phase
Dosimetry Healthy	Drug: [C-11](R)-rolipram	Phase I

Study Type:	Interventional
Study Design:	Treatment
Official Title:	PET Whole Body Biodistribution and Test Retest Brain Imaging Studies Using a Phosphodiesterase 4 Inhibitor (R)-[11C]Rolipram

Resource links provided by NLM:

Drug Information available for: Rolipram

U.S. FDA Resources

Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment:	35
Study Start Date:	October 2005
Study Completion Date:	February 2009
Primary Completion Date:	February 2009 (Final data collection date for primary outcome measure)

Intervention Details:

N/A

Detailed Description:

Both basic and clinical studies have indicated that the 3', 5'-cyclic adenosine monophosphate (cAMP) system plays critical roles in several brain diseases, particularly in mood disorders and drug addiction. cAMP is synthesized from adenosine 5'-triphosphate (ATP) by adenylyl cyclase and metabolized by cyclic nucleotide phosphodiesterases (PDEs). Among components of the cAMP pathway, PDE4 appears to be critical for antidepressant effects.

4-[3-(cyclopentoxyl)-4-methoxyphenyl]-2-pyrrolidone (rolipram) is an inhibitor of PDE4. As a positron emission tomography (PET) brain imaging agent, rolipram has good properties such as high affinity of 1-2 nM and appropriate lipophilicity (Log P) of ~3. A rat study gave an estimation of low radiation absorbed doses of the active enantiomer (R)-[11C]rolipram. ciociWEge quality. Therefore, R-[11C]rolipram is a promising PET ligand.

However, radiation absorbed doses have not been estimated from human whole body imaging studies and a method to measure binding of (R)-[11C]rolipram in human brain has not been established.

The purposes of this protocol are to estimate radiation absorbed doses of (R)-[11C]rolipram by performing whole body imaging studies on healthy human subjects and also to establish an accurate method to measure PDE4 levels in brain by performing test retest brain imaging studies. The results of this overall study are required to apply this PET ligand in various neurological and psychiatric disorders in the future.

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

INCLUSION CRITERIA:

All subjects must be healthy and aged 18-65 years.

EXCLUSION CRITERIA:

PART 1 (WHOLE BODY IMAGING STUDIES):

Current psychiatric disease, substance abuse or severe systemic disease based on history and physical exam, poor vision or hearing.
Laboratory tests with clinically significant abnormalities.
Prior participation in other research protocols or clinical care in the last year such that radiation exposure including that from this protocol would exceed a half of the annual limits. Because human dosimetry of (R)-[(11)C]rolipram has been estimated using rhesus monkeys, the total exposure including that from the (R)-[(11)C]rolipram whole body imaging study will be limited to a half of the RSC guidelines.
Pregnancy and breast feeding.
Positive HIV test.
Positive urine drug screen.

PART 2 (TEST RETEST BRAIN IMAGING STUDIES):

Current psychiatric disease, substance abuse or severe systemic disease based on history and physical exam, poor vision or hearing.
Laboratory tests with clinically significant abnormalities.
Prior participation in other research protocols or clinical care in the last year such that radiation exposure would exceed the annual limits. Results of part 1 will be used to calculate total radiation exposure within a year.
Pregnancy and breast feeding.
Claustrophobia.
Presence of ferromagnetic metal in the body or heart pacemaker.
Positive HIV test.
A history of brain disease.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00250172

Locations

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892

Sponsors and Collaborators

National Institute of Mental Health (NIMH)

More Information

Additional Information:

NIH Clinical Center Detailed Web Page This link exits the ClinicalTrials.gov site

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.

Cloutier RJ, Smith SA, Watson EE, Snyder WS, Warner GG. Dose to the fetus from radionuclides in the bladder. Health Phys. 1973 Aug;25(2):147-61. No abstract available.

Conti M, Nemoz G, Sette C, Vicini E. Recent progress in understanding the hormonal regulation of phosphodiesterases. Endocr Rev. 1995 Jun;16(3):370-89. Review. No abstract available.

Study ID Numbers:	060002, 06-M-0002
Study First Received:	November 5, 2005
Last Updated:	August 24, 2009
ClinicalTrials.gov Identifier:	NCT00250172 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):

Dosimetry
Pharmacokinetics
Compartment Analysis

Reproducibility
Healthy Volunteer
HV

Study placed in the following topic categories:

Rolipram
Phosphodiesterase Inhibitors
Psychotropic Drugs
Healthy
Antidepressive Agents

Additional relevant MeSH terms:

Rolipram
Phosphodiesterase Inhibitors
Molecular Mechanisms of Pharmacological Action
Therapeutic Uses
Psychotropic Drugs

Enzyme Inhibitors
Central Nervous System Agents
Pharmacologic Actions
Antidepressive Agents

ClinicalTrials.gov processed this record on September 10, 2009