Acute Effects of Alcohol on PET Imaging of Phosphodiesterase-4B (PDE4B)
2 other identifiers
interventional
30
1 country
1
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Dec 2025
Typical duration for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 17, 2025
CompletedFirst Posted
Study publicly available on registry
June 19, 2025
CompletedStudy Start
First participant enrolled
December 11, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 22, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
February 22, 2029
April 17, 2026
April 8, 2026
2.2 years
June 17, 2025
April 16, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
To measure distribution volume
Target quantification
36 months
Study Arms (1)
One arm
EXPERIMENTALAll subjects will receive 18F-PF-06445974. In addition to 18F-PF-06445974 some subjects may receive ethanol infusion.
Interventions
Eligibility Criteria
You may qualify if:
- To be eligible to participate in this study, an individual must meet the following criteria:
- Be enrolled in protocol 14-AA-0181, NIAAA Natural History Protocol.
- Age 21 - 70 years.
- Willingness to complete the study including MRI tests.
- Be in good general health as evidenced by medical history and physical examination.
- Participants must 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.
- Able to provide informed consent.
You may not qualify if:
- An individual who meets any of the following criteria will be excluded from participation in this study:
- History of AUD or SUD. Participants may currently use cannabis recreationally but cannot meet criteria for cannabis use disorder, or present for study visits with positive urine drug screen for THC.
- Current non-drinkers (alcohol-naive individuals or no use of alcohol in the past year), or individuals with no experience drinking 5 or more drinks on one occasion in their lifetime.
- Current or prior history of alcohol-induced flushing reactions, including rapid reddening of the face, rapid heart rate and breathing, and nausea after 1 or 2 drinks.
- Clinically significant abnormalities on EKG or laboratory tests: CBC and acute care panel (Na, K, Cl, CO2, creatinine, glucose, urea nitrogen), liver function tests (GGT, AST, ALT, bilirubin).
- Participants who have taken an antipsychotic or antidepressant medication within two weeks prior to the PET scan #1, with longer washout times of 1 month for antidepressants with longer half-lives such as fluoxetine. In addition, they will be withdrawn if they begin these medications during the two PET scans.
- a. Use of prescription or OTC medication known to interact with alcohol 2 weeks prior to screening or screening update visit. These include but may not be limited to: isosorbide; nitroglycerine; benzodiazepines; warfarin; anti-depressants such as amitriptyline, clomipramine and nefazodone; anti-diabetes medications such as glyburide, metformin and tolbutamide; H2-antagonists for heartburn such as famotidine, cimetidine and ranitidine; muscle relaxants; anti-epileptics including phenytoin and phenobarbital; codeine and opioid analgesics including Darvocet, Percocet and hydrocodone.
- b. Regular (more than once a week) or prescribed use of antihistamines, pain medicines, and anti-inflammatories such as aspirin, ibuprofen, acetaminophen, celecoxib, and naproxen, and unable to refrain from these medications for 48 hours prior to study visits
- c. Use of medications known to inhibit or induce enzymes that metabolize alcohol for 4 weeks prior to screening or screening update visit. These include chlorzoxazone, isoniazid, metronidazole, and disulfiram.
- \) HIV infection.
- \) Pregnancy or breast feeding.
- \) Have recent exposure to radiation related to research (e.g., PET from other research) that, when combined with this study, would be above the allowable limits.
- \) Have an inability to lie flat and/or lie still on the camera bed for two hours, including claustrophobia, overweight greater than the maximum for the scanner, and uncontrollable behavioral symptoms, which will be screened by an interview with the participant during the screening visit.
- \) 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
Related Links
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Robert B Innis, M.D.
National Institute of Mental Health (NIMH)
Central Study Contacts
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
June 17, 2025
First Posted
June 19, 2025
Study Start
December 11, 2025
Primary Completion (Estimated)
February 22, 2028
Study Completion (Estimated)
February 22, 2029
Last Updated
April 17, 2026
Record last verified: 2026-04-08
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL
- Time Frame
- 18 months after closure of protocol.
- Access Criteria
- De-identified data can be accessed through NIH Biomedical Translational Research Information System (BTRIS).
This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule.