PET Brain and Whole Body Distribution Studies for Nociceptin/Orphanin FQ Peptide (NOP) Receptor Using [11C]NOP-1A

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT01198197
First received: September 8, 2010
Last updated: September 6, 2014
Last verified: September 2014
  Purpose

Background:

- A small brain protein called nociceptin/orphanin FQ peptide (NOP) receptor may be involved in several brain diseases such as anxiety, depression, drug abuse, and seizures. Researchers are interested in testing a new radioactive chemical that will help locate NOP receptors in the brain during imaging studies such as positron emission tomography (PET) scans. Because this chemical has not yet been approved by the Food and Drug Administration, it is considered to be an experimental drug.

Objectives:

- To investigate the effectiveness of the experimental chemical [11C]NOP-1A in imaging studies of the nociceptin/orphanin FQ peptide (NOP) receptor.

Eligibility:

- Healthy volunteers between 18 and 50 years of age who are able to have imaging studies.

Design:

  • This study will involve three or four outpatient visits to the National Institutes of Health Clinical Center. All participants will be screened with a full physical examination, medical history, blood and urine tests, and electrocardiogram.
  • Participants will be involved in one or more parts of this three-part study as directed by study researchers. Part 1 consists of brain imaging to study how the brain responds to the chemical. Part 2 is a whole body imaging study to evaluate how the chemical is distributed throughout the body after being administered. Part 3 is a set of testing and retesting scans to determine how precise the drug is in locating the NOP receptors in the brain.
  • Part 1: Participants will have a brain magnetic resonance imaging (MRI) scan. Then the study drug will be administered and participants will have a brain PET scan. Blood samples will be taken during the PET scan, and urine samples will be taken after the scan. These tests will take up to 3 hours to perform.
  • Part 2: Participants will have a whole body PET scan that will last a maximum of 3 hours.
  • Part 3: Participants will receive the study drug and have two additional PET scans. Blood samples will also be taken during this part.

Condition Intervention Phase
Pain
Anxiety
Depression
Drug: NOP-1A
Phase 0

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: PET Brain and Whole Body Distribution Studies for Nociceptin/Orphanin FQ Peptide (NOP) Receptor Using [(11)C]NOP-1A

Resource links provided by NLM:


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

Primary Outcome Measures:
  • For the PET scans, we will measure the regional densities of NOP receptors as distribution volume (VT). Distribution volume is the ratio at equilibrium of brain uptake to the concentration of parent radioligand in plasma. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Enrollment: 41
Study Start Date: September 2010
Study Completion Date: February 2014
Intervention Details:
    Drug: NOP-1A
    N/A
Detailed Description:

Nociceptin/orphanin FQ peptide (NOP) receptor is a new class of opioid receptor cloned in 1994 before identifying the endogenous ligand. Within a year, endogenous ligand was identified and soon many ligands were developed and evaluated in vitro and in vivo for NOP receptor distribution and activity. NOP receptor is widely distributed in brain, spinal cord and in peripheral organs such as heart, lungs, kidney, intestine and liver. Being a G-protein coupled receptor, its activation leads to changes in intracellular signal transduction mediated by adenylyl cyclase, Ca(2+) and K(+) ion channels, mitogen-activated kinase and phospholipase C. Based on preclinical studies, NOP receptor is implicated in regulation of pain, anxiety and depression, drug abuse, feeding, learning/memory, and motor activity.

Since the time of cloning the receptor and identification of endogenous ligand, numerous compounds have been designed targeting this receptor. However, there are no PET radioligands currently available to study NOP distribution and activity in humans. We wish to test a newly developed PET radioligand, [(11)C]NOP-1A to study the role of NOP receptors in humans.

The purpose of this protocol is (1) to perform brain imaging using [(11)C]NOP-1A in healthy volunteers to characterize the brain uptake and distribution (2) to perform whole body PET studies in healthy volunteers in order to estimate radiation absorbed doses for [(11)C]NOP-1A, (3) to perform brain test-retest studies in healthy volunteers in order to further examine the precision of the measurement of receptor binding and to determine optimal parameters for future experiments using [(11)C]NOP-1A, and, (4) to compare [(11)C]NOP-1A concentrations in artery and vein of healthy volunteers to assess the feasibility of replacing the arterial line with a less invasive venous line for brain scans.

Successful development of a PET radioligand to image NOP receptor will have a strong impact on further understanding and clinical management of neuropsychiatric disorders that are mediated by opioid receptor system. Future experiments will include studies on any relevant neuropsychiatric disorder.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

Healthy Volunteers:

Subjects must be adults between 18-50 years old.

Subjects must be able and willing to give written informed consent.

EXCLUSION CRITERIA:

Current psychiatric illness or severe systemic disease based on history and physical exam.

If women, pregnancy or breast feeding (betaHCG will be measured in all female patients within 24 hours of scan and must be negative)

Clinically significant laboratory abnormalities.

Serious medical problems including but not limited to chronic neurological disease such as multiple sclerosis, autoimmune diseases or any cardiopulmonary disease.

Head trauma resulting in a period of unconsciousness lasting longer than 10 minutes.

Recent exposure to radiation (i.e., PET from other research) which when combined with this study would be above the allowable limits.

Positive urine drug screen at screening.

Inability to lie flat on camera bed for about 2.5 hours

Subjects who have metallic foreign bodies that would be affected by the MRI magnet, or fear of enclosed spaces likely to make the subject unable to undergo an MRI scan.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01198197

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Investigators
Principal Investigator: Masahiro Fujita, M.D. National Institute of Mental Health (NIMH)
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT01198197     History of Changes
Other Study ID Numbers: 100204, 10-M-0204
Study First Received: September 8, 2010
Last Updated: September 6, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Nociceptin/Orphanin FQ Peptide (NOP)
PET Imaging
Brain Imaging
Healthy Volunteer
HV

Additional relevant MeSH terms:
Anxiety Disorders
Depression
Depressive Disorder
Mental Disorders
Behavioral Symptoms
Mood Disorders
Nociceptin
Vasodilator Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 14, 2014