PET Imaging of Phosphodiesterase-4B (PDE4B) in Alcohol Use Disorder

Phase 1

Recruiting

• Conditions: Alcohol Use Disorder
• Interventions: Drug: 18F-PF-06445974

• Registration Number: NCT06795581
• Lead Sponsor: National Institute of Mental Health (NIMH)

Brief Summary

Background:

People with alcohol use disorder (AUD) also often have bouts of depression called major depressive episodes (MDEs). People having MDEs have been found to have low levels of a protein called PDE4B in the brain. Researchers want to find out if people with AUD also have low levels of PDE4B. This research may help lead to better treatments for AUD.

Objective:

To find out (1) if PDE4B levels are lower in people who are withdrawing from AUD and (2) if their PDE4B levels go up after they abstain from alcohol for 3 to 4 weeks.

Eligibility:

Adults aged 18 to 70 years with AUD. They must be enrolled in protocol 14-AA-0181.

Design:

Participants enrolled in protocol 14-AA-0181 will stay in the clinic for 3 to 4 weeks for alcohol withdrawal. During this stay, they will have some added procedures for the current study.

Within the first week, participants will have a positron emission tomography (PET) scan of the brain. 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 will be injected through the catheter. This tracer binds to PDE4B and makes it easier to see the protein in the brain. For the scan, participants will lie on a table that slides into a doughnut-shaped machine.

Participants will have a second PET scan toward the end of their stay in the clinic.

Participants may also have a magnetic resonance imaging (MRI) scan of the brain. They will lie on a bed that slides into a tube.

Detailed Description

Study Description:

AUD participants will be referred from protocol 14-AA-0181, which includes a four-week hospitalization at NIH for alcohol withdrawal. Using the PET radioligand \[18F\]PF974 to measure the density of PDE4B, AUD participants will be scanned twice: 1) within one week of admission, and 2) after 3-4 weeks of alcohol withdrawal.

Objectives:

Primary Objective #1: To determine whether PDE4B radioligand binding is decreased in AUD participants during acute withdrawal compared to healthy volunteers matched as a group for age and sex.

Primary Objective #2: To determine whether PDE4B radioligand binding increases in individuals on the second scan compared to the first.

Secondary Objective: No exploratory correlations are hypothesized for this novel imaging of PDE4B. However, we may later perform correlations with any of the clinical parameters or biological biomarkers obtained in the 14- AA-0181. Note that Dr. Diazgranados is an AI of this PET protocol, and Dr. Innis will become an AI of the parent protocol.

Endpoints:

Primary endpoint: For both objectives, the primary endpoint is PET measurement of PDE4B binding (VT) in all regions of the brain.

Study Timeline

• Study First Submitted: 2025-01-25
• Study First Submitted QC: 2025-01-25
• Study Start: 2025-03-20
• Status Verified: 2025-03-24
• Study First Posted: 2025-03-25
• Last Update Submitted: 2025-03-25
• Last Update Posted: 2025-03-26
• Primary Completion: 2028-12-11
• Study Completion: 2029-01-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
One-arm	18F-PF-06445974	All subjects will receive the same tests.

Primary Outcome Measures

Name	Time	Method
To measure distribution volume	36 months	Target quantification

Trial Locations

Locations (1)

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