First-in-Human Evaluation of [11C]JMJ-129-d2 for PDE-4D Imaging in Healthy Volunteers

NCT07853781 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 10002720002720-M
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Background: PDE-4D is a protein found in the brain. It helps control chemical signals that affect mood, memory, and thinking. Problems with PDE-4D may play a role in depression and Alzheimer disease. Being able to measure PDE-4D levels in the body would help doctors identify and manage these diseases. Researchers want to find out if a new tracer (a radioactive substance injected during imaging scans) can help them see PDE-4D in people more effectively. Objective: To test a new tracer (\[11C\]JMJ-129-d2) during imaging scans of the brain and body in healthy people. Eligibility: Healthy people aged 18 years and older. They must have been screened under protocols 01M0254 or 17M0181. Design: All participants will give samples of blood and urine. They will have a test of their heart function. A plastic tube will be inserted into a vein in their arm; the new tracer will be given through this tube. Some participants will have 1 positron emission tomography (PET)/computed tomography (CT scan of their whole body. They will lie on a padded bed that slides into a doughnut-shaped machine; the machine uses x-rays to create images of the inside of the body. Some participants will have 1 or 2 PET/CT scans of their brain only. Their head will be supported to keep it still during the scan. They will also have a magnetic resonance imaging (MRI) scan of the brain. MRI uses magnetic fields to capture images of the inside of the body. The MRI scan may require a second visit. All participants will receive a follow-up call to check on their well-being 2 or 3 days after their scans.

Conditions

Healthy

Keywords

Kinetic Modeling; Dosimetry; Whole-body imaging; Brain Imaging; Phosphodiesterase 4D (PDE4D); Positron Emission Tomography (PET)/CT Imaging; 11C-JMJ-129-d2

Outcome Measures

Primary Outcomes (1)

• Total Volume of Distribution

  Regional VT from kinetic modeling

  120 minutes

Secondary Outcomes (1)

• Dosimetry, ICC, aTRV, and biodistribution

  120 minutes

Study Arms (1)

One-arm

OTHER

All subjects will receive the same tests.

Drug: [11C]JMJ-129-d2

Interventions

[11C]JMJ-129-d2 DRUG

Injected IV followed by PET scanning

One-arm

Eligibility Criteria

• Age: 18 Years - 105 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• In order to be eligible to participate in this study, an individual must meet all of the following criteria:
• Provision of signed and dated informed consent under this protocol.
• Successful completion of screening under protocol 01M0254 or 17M0181 and confirmation of eligibility.
• Age 18 years or older.
• In good general health as determined by medical history, physical examination, vital signs, laboratory testing, and electrocardiogram.
• Willingness and ability to comply with all study procedures.
• 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

You may not qualify if:

• 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).
• Any current DSM-5-TR persistent psychiatric disorder, including but not limited to: schizophrenia spectrum and other psychotic disorders; bipolar and related disorders; and depressive disorders.
• 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) which 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 breast feeding.
• Participants must not have substance use disorder or alcohol use disorder.
• Unable to travel to the NIH.
• Are 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, crisaborole).
• Current use of any PDE4 inhibitor (e.g., apremilast, roflumilast, crisaborole), or use within 7 days prior to PET imaging.
• 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, which may alter the metabolism and affect the kinetics of the study drug.

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

Study Officials

• Robert B Innis, M.D.

  National Institute of Mental Health (NIMH)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tara N Turon, C.R.N.P.

CONTACT

(301) 827-6599; tara.turon@nih.gov

Robert B Innis, M.D.

CONTACT

(301) 594-1368; robert.innis@nih.gov

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 1, 2026
• First Posted: October 2, 2026
• Study Start (Estimated): October 26, 2026
• Primary Completion (Estimated): February 22, 2030
• Study Completion (Estimated): February 5, 2031
• Last Updated: October 2, 2026

Record last verified: 2026-09-24

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: 18 months after closure of protocol.
• Access Criteria: BTRIS

Locations

US (1)