NCT05703685

[18F]PF-06445974 to Image PDE4B in Major Depressive Disorder Using PET

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 108 (estimated)
• Sponsor: National Institute of Mental Health (NIMH) · NIH
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Accepted

Summary

Background: Major depressive disorder (MDD) is a psychiatric condition. People with MDD have occasional bouts of depressive symptoms; these bouts are called major depressive episodes (MDEs). Researchers want to know if people having MDEs have lower levels of an enzyme called PDE4B in their brains. Primary Objective: To determine whether PDE4B is reduced in the brains of individuals with MDD experiencing a major depressive episode (MDE). Secondary Objectives: To determine the optimal length of scanning and the retest variability and reliability of \[18F\]PF-06445974, and whether PDE4B binding correlates with clinical rating scales. To measure if PDE4B radioligand binding can be blocked by taking apremilast. Eligibility: People aged 18-70 years with MDD. Healthy volunteers are also needed. Design: Participants will have up to 5 clinic visits. Participants will be screened. They will have a physical exam with blood tests. They will have a test of their heart function. Some participants may have a psychiatric assessment; they will answer questions about their state of mind and related topics. Participants will have magnetic resonance imaging (MRI) of the brain. They will lie on a table that slides into a metal cylinder. Participants will have a positron emission tomography (PET) scan. A needle will be used to guide a thin plastic tube (catheter) into a vein in one arm. An experimental substance called a radioactive tracer (\[18F\]PF-06445974) will be injected through the catheter. Participants will lie on a table that slides into a doughnut-shaped machine. The scan will last up to 4 hours with a 15-minute break. Participants blood pressure, heart rate, and breathing will be monitored before, during, and after the PET scan. A second catheter will be inserted in the artery of the wrist so blood can be drawn during the scan. Some participants may return for a second PET scan; have a lung scan or receive apremilast. https://nimhcontent.nimh.nih.gov/start/surveys/?s=KE88DXXPLDFHHTF8

Detailed description

Study Description: This study will examine whether phosphodiesterase 4B (PDE4B) can be accurately quantified in the human brain and whether it is reduced in the brain of individuals with major depressive disorder (MDD). Objectives: Primary Objective: To determine whether PDE4B is reduced in the brains of individuals with MDD experiencing a major depressive episode (MDE). Secondary Objectives: To determine the optimal length of scanning and the retest variability and reliability of \[18F\]PF-06445974, and whether PDE4B binding correlates with clinical rating scales. Endpoints: Primary Endpoint: measurement of PDE4B density (distribution volume VT) in the brains of individuals with MDD compared to healthy volunteers Secondary endpoints: 1. To determine the optimal length for PDE4B scans with \[18F\]PF-06445974 PET scans in healthy volunteers 2. To measure whole-brain VT of PDE4B in a retest setting. 3. To assess the relationship between clinical rating scales and PDE4B binding. 4. To measure the blockade of PDE4B radioligand binding in brain after oral administration of apremilast.

Conditions

• Depression

Interventions

Type	Name	Description
RADIATION	Lung scan	Immediately after the brain scan
DRUG	Apremilast	Oral administration of apremilast
DRUG	18F-PF-06445974	Injected IV followed by PET scanning

Timeline

• Start date: 2023-06-22
• Primary completion: 2028-10-03
• Completion: 2029-04-11
• First posted: 2023-01-30
• Last updated: 2025-12-08

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study