Evaluation of [11C]ZTP-1 to Image PDE4B

Phase 1RecruitingNCT07625345

National Institute of Mental Health (NIMH)40 enrolled

Overview

Background: PDE4B is a protein in cells that helps turn off certain chemical signals after they ve done their job. It controls inflammation, immune responses, and some brain signaling. Measuring PDE4B levels in the body can help doctors manage a disease or know if a treatment is working. Researchers want to find out if a new tracer (a radioactive substance injected during imaging scans) can help them measure PDE4B in people more effectively. Objective: To test a new tracer (\[11C\]ZTP-1) during imaging scans of the brain and body in healthy people. Eligibility: Healthy people aged 18 and older. They must have been screened under protocols 01M-0254 or 17M0181. Design: Participants will have either 1 or 2 clinic visits. During their first visit, all participants will have a positron emission tomography (PET)/computed tomography (CT) scan. Prior to the scan, they will have blood and urine tests and a test of their heart function. The study tracer will be given through a tube attached to a needle inserted into a vein in the arm. They will lie on a padded bed that fits inside a doughnut-shaped machine; the machine uses x-rays to create images of the inside of the body. Some participants will have a PET/CT scan of their whole body. They will need only 1 visit. The visit will last up to about 8 hours. Some participants will have a PET/CT scan of only their brain. They will also have a magnetic resonance imaging (MRI) scan of the brain. They may need to return for a second visit for the MRI scan. Participants will receive a follow-up call to check on their well-being after their PET/CT scans.

Study Description: This study is intended to provide information on the novel \[11C\]ZTP-1 radioligand and its ability to localize and measure PDE4B in the brain and body of healthy volunteers. Objectives: Primary Objective: To study the brain uptake of \[11C\]ZTP-1 and perform kinetic modeling of \[11C\]ZTP-1 in healthy volunteers. Secondary Objective: To study brain retest variability and reliability, biodistribution, and dosimetry of \[11C\]ZTP-1 in healthy volunteers. Endpoint: Primary Endpoint: PDE4B density measured as distribution volume (VT), derived from kinetic modeling of \[11C\]ZTP-1 in the brain. Secondary Endpoint: PDE4B density measured as distribution volume (VT) , evaluated in terms of test retest variability (absolute variability) and reliability (intraclass correlation coefficient \[ICC\]). Whole-body biodistribution and radiation burden, measured as Effective Dose (ED).)

Study Type

INTERVENTIONAL

Eligibility

Sex: ALLMin age: 18 YearsMax age: 101 YearsHealthy volunteers:

Medical Language ↔ Plain English

* INCLUSION CRITERIA: To be eligible to participate in this study, an individual must meet the following criteria: * Aged 18 years or older. * Must have undergone a screening assessment under protocol 01M-0254, "The Evaluation of Patients with Mood and Anxiety Disorders and Healthy Participants or protocol 17M0181 Recruitment and Characterization of Healthy Research Volunteers for NIMH Intramural Studies." * Be healthy based on medical history, physical examination, and laboratory testing. * Able to provide informed consent. * Willingness to complete all study procedures including MRI tests. * Have had their radial artery pulse checked for the presence of adequate ulnar collateral flow and the absence of any metal or foreign objects in both wrists. * Agree to adhere to the lifestyle considerations EXCLUSION CRITERIA: An individual who meets any of the following criteria will be excluded from participation in this study: * Clinically significant abnormalities on EKG or laboratory testing. This includes CBC and acute care panel (Na, K, Cl, CO2, creatinine, glucose, urea nitrogen). * History of neurologic illness or injury with the potential to affect study data interpretation. * History of seizures, other than in childhood and related to fever. * Recent exposure to radiation (i.e., PET from other research) that, when combined with this study, would be above the allowable limits. * Inability to lie flat on camera bed for at least two hours, including claustrophobia and weight greater than the maximum for the scanner (500 lbs). * HIV infection. * Pregnancy or breastfeeding. * Must not have substance use disorder or alcohol use disorder. * Unable to travel to the NIH. * Unable to have an MRI scan (e.g., because of pacemakers or other implanted electrical devices, brain stimulators, dental implants, aneurysm clips (metal clips on the wall of a large artery), metallic prostheses (including metal pins and rods, heart valves, and cochlear implants), permanent eyeliner, implanted delivery pumps, shrapnel fragments, or metal fragments in the eye. * Known hypersensitivity to phosphodiesterase-4 (PDE-4) inhibitors (e.g. apremilast, roflumilast, nerandomilast, crisborole). * Taking CYP3A4 inhibitors (e.g. grapefruit juice, clarithromycin, erythromycin, ritonavir); CYP3A4 inducers (e.g. phenobarbital St. John's Wort, rifampicin) or oral contraceptives containing gestodene and ethinyl estradiol. EXCLUSION OF CHILDREN: Inclusion of children is not appropriate, because this protocol has more than minimal risk from radiation exposure without the possibility of direct benefit. EXCLUSION OF PREGNANT OR BREASTFEEDING WOMEN: Pregnant women will be excluded because this protocol involves exposure to ionizing radiation. Lactating women will be excluded because radioisotopes may be excreted in milk. We will perform a pregnancy test at screening and prior to all procedures to ensure participants are not pregnant. The test must be negative in order to continue on the study. In addition to completing a negative urine pregnancy test, on the day of PET scanning prior to PET scan procedures, participants of childbearing potential will undergo a clinical pregnancy screening interview with a licensed independent practitioner to confirm lack of pregnancy. EXCLUSION OF PARTICIPANTS WHO ARE HIV POSITIVE: Persons with HIV infection are excluded because HIV infection itself may change cAMP signaling.

Evaluation of [11C]ZTP-1 to Image PDE4B

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts