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

Early Phase 1

Completed

• Conditions: Pain; Anxiety; Depression

• Registration Number: NCT01198197
• Lead Sponsor: National Institute of Mental Health (NIMH)

Brief Summary

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.

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.

Study Timeline

• Study Start: 2010-09-03
• Study First Submitted: 2010-09-08
• Study First Submitted QC: 2010-09-08
• Study First Posted: 2010-09-09
• Study Completion: 2014-02-28
• Status Verified: 2014-09-05
• Last Update Submitted: 2019-12-14
• Last Update Posted: 2019-12-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 41

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
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.	2 years

Trial Locations

Locations (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike; 🇺🇸 Bethesda, Maryland, United States