NCT07169630

PET Imaging of Phosphodiesterase-4 (PDE4) in Volunteers With Alzheimer Disease (AD) or Mild Cognitive Impairment (MCI)

PET Imaging of Phosphodiesterase-4 (PDE4) in Volunteers With Alzheimer s Disease (AD) or Mild Cognitive Impairment (MCI)

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 90 (estimated)
• Sponsor: National Institute of Mental Health (NIMH) · NIH
• Sex: All
• Age: 50 Years – 100 Years
• Healthy volunteers: Accepted

Summary

Background: About 5 million adults in the United States have age-related brain disorders. These include Alzheimer disease (AD), mild cognitive impairment (MCI), and other dementias. The number of people with these disorders will likely increase as the population ages and life span increases. Inflammation is thought to play a role in AD and MCI. Researchers want to know if an enzyme called PDE4B increases inflammation in people with AD or MCI. Objective: To test whether medical imaging using a new radiotracer (\[18F\]PF-06445974) can measure PDE4B in the brains of people with AD or MCI. Eligibility: People aged 50 years and older with AD or MCI. Healthy volunteers are also needed. Design: Participants will have up to 5 clinic visits with 3 imaging scans of the brain. They will have be screened. They will have a physical exam with blood tests. This will include tests of their heart and nerve function, including memory. Participants will have 2 positron emission tomography (PET) scans. One will use a standard radiotracer. The other will use the study radiotracer. They will receive each tracer through a tube attached to a needle inserted into a vein. During the scan with the study tracer, participants will have a second tube inserted into a vein in the wrist; this tube will be used to draw blood during the scan. Participants will lie on a bed that slides into a doughnut-shaped machine. These visits will take about 6 hours each. Participants will have 1 magnetic resonance imaging (MRI) scan. They will lie on a bed that slides into a cylinder. This visit will take up to 2 hours....

Detailed description

Study Description: As a biomarker of neuroinflammation, the density of PDE4B is hypothesized to be elevated in individuals with AD or MCI compared to age-matched healthy volunteers (HVs). Participants will receive two positron emission tomography (PET) scans (for PDE4B and for beta-amyloid (A beta)) and one magnetic resonance imaging (MRI) scan of the brain. Objectives: Primary Objective: To determine whether PDE4B radioligand binding is increased in medial temporal lobe of participants with AD or MCI (both A beta positive) compared to age-and sex matched HVs (who are A beta negative) Exploratory Objective #1: To determine whether PDE4B binding in the medial temporal lobe is correlated with demographic variables, clinical markers, or biological markers. Exploratory Objective #2: To determine whether any region of the brain in individuals with AD or MCI has increased PDE4B binding compared to HVs. Endpoints: Primary endpoints: PET measurements of PDE4B; clinical variables, including neuropsychological tests; and biological variables, including plasma concentrations of A(beta)40, A(beta)42, total tau, and Ptau217.

Conditions

• Alzheimer s Disease
• Mild Cognitive Impairment
• Healthy

Interventions

Type	Name	Description
DRUG	18F-PF974	Injected IV followed by PET scanning
DRUG	18F-florbetaben	Injected IV followed by PET scanning

Timeline

• Start date: 2026-04-22
• Primary completion: 2029-04-11
• Completion: 2030-04-11
• First posted: 2025-09-12
• Last updated: 2026-04-17

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study