Acute Effects of Alcohol on PET Imaging of Phosphodiesterase-4B (PDE4B)

Phase 1

Recruiting

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

• Registration Number: NCT07027839
• Lead Sponsor: National Institute of Mental Health (NIMH)

Brief Summary

Background:

Phosphodiesterase-4B (PDE4B) is a protein in the brain that may play a role in several mental health disorders. Researchers want to know if drinking alcohol increases the binding of a radioactive tracer to PDE4B in the brain because of increased activity and/or amount of the protein. This knowledge may help create new ways to treat people with alcohol use disorder (AUD).

Objective:

To learn if alcohol increases PDE4B activity in the brain.

Eligibility:

Healthy people aged 21 to 70 years who drink socially but do not have AUD. They must be enrolled in protocol 14-AA-0181"NIAAA Natural History Protocol".

Design:

Participants will have up to 4 clinic visits with up to 3 imaging scans of the brain; these will include 1 or 2 positron emission tomography (PET) scans and 1 magnetic resonance imaging (MRI) scan.

The first PET scan will be a baseline. Participants will receive a radioactive tracer through a tube inserted into a vein. A second tube will be inserted so that blood can be drawn during the scan. Participants will lie on a bed that slides into a doughnut-shaped machine. This visit will take about 6 hours.

For the next PET scan, participants will receive alcohol (ethanol) through a tube in a vein until they have a blood alcohol concentration that is equal to the legal driving limit. This is the same as 4 or 5 drinks for most people. After the scan, participants must remain at the clinic for a few hours until their blood alcohol drops. This visit will take 14 to 16 hours.

The MRI scan of the brain will take up to 2 hours in a separate clinic visit.

Detailed Description

Study Description:

Alcohol drinkers with no history of AUD will be enrolled from protocols 14-AA-0181 or 000676. Using the PET radioligand \[18F\]PF-06445974 (Hereafter referred to as \[18F\]PF974) to measure PDE4B binding in the brain, 14-AA-0181 participants will be scanned twice: at baseline and during an intravenous infusion of ethanol to achieve a target breath alcohol concentration (BrAC) of 0.08 g% (80 mg/dL). Participants from protocol 000676 will have already had the baseline scan with \[18F\]PF974 and will only be scanned during an intravenous infusion of ethanol.

Objectives:

Primary Objective: Using a within-subject design, to determine whether acute ethanol administration increases PDE4B binding in whole brain.

Secondary Objective:

To determine whether PDE4B radioligand binding increases in all regions of the brain

Endpoints:

The primary endpoint is the PET measurement of PDE4B binding (VT) in whole brain and in regions of the brain.

Study Timeline

• Study First Submitted: 2025-06-17
• Study First Submitted QC: 2025-06-18
• Study First Posted: 2025-06-19
• Status Verified: 2025-07-22
• Last Update Submitted: 2025-08-05
• Last Update Posted: 2025-08-06
• Study Start: 2025-08-11
• Primary Completion: 2028-02-22
• Study Completion: 2029-02-22

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	Intravenous Ethanol	All subjects will receive 18F-PF-06445974. In addition to 18F-PF-06445974 some subjects may receive ethanol infusion.
One arm	18F-PF-06445974	All subjects will receive 18F-PF-06445974. In addition to 18F-PF-06445974 some subjects may receive ethanol infusion.

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