Alcohol Use DisorderPhase 1NCT07027839
Acute Effects of Alcohol on PET Imaging of Phosphodiesterase-4B (PDE4B)
A Phase 1 study testing Intravenous Ethanol and 18F-PF-06445974 in people with Alcohol Use Disorder, run by National Institute of Mental Health (NIMH) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 70 years
- Conditions the study is for
- Alcohol Use Disorder
- What is being tested?
- Intravenous Ethanol and 18F-PF-06445974
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Dec 2025to 22 Feb 2029
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- Medication exclusion for alcohol:
- 6a. 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.
- 6b. 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
- 6c. 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.
- 7) HIV infection.
- 8) Pregnancy or breast feeding.
- 9) 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.
- 10) 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.
- 11) 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
NIH Clinical Center Office of Patient Recruitment (OPR), 800-411-1222 ext. TTY dial 711, ccopr@nih.gov
About this study
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).
Read more
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.
Read the 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 following intravenous administration of ethanol to achieve a target breath alcohol concentration (BrAC) of 0.08 g% (80 mg/dL). For the ethanol condition, alcohol will be administered intravenously prior to PET acquisition to reach and stabilize the target BrAC. PET imaging will then be conducted without concurrent ethanol infusion. Participants from protocol 000676 will have already had the baseline scan with [18F]PF974 and will only undergo a single PET scan following intravenous ethanol
administration as described.
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.
- Conditions
- Alcohol Use Disorder
- Being tested
- Intravenous Ethanol, 18F-PF-06445974
- Keywords
- PET Imaging, Alcohol Use Disorder (AUD), Phosphodiesterase-4B (PDE4B)
- Medical subject headings
- Alcoholism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intravenous EthanolDrug
Intravenous ethanol infusion before PET Scan
18F-PF-06445974Drug
Injected IV followed by PET scanning
| Study group | Role | What they receive |
|---|---|---|
| One arm | Experimental | All subjects will receive 18F-PF-06445974. In addition to 18F-PF-06445974 some subjects may receive ethanol infusion. Receives: Drug: Intravenous Ethanol; Drug: 18F-PF-06445974 |
What is being measured
The primary outcome is the main question the study is designed to answer.
To measure distribution volume
Target quantification
Measured: 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jun 2025
- Study start11 Dec 2025
- Primary completion22 Feb 2028 (estimated)
- Study completion22 Feb 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alcohol Use DisorderStudies of the same condition, open and under way.
- More trials run by National Institute of Mental Health (NIMH)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Institute of Mental Health (NIMH)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Robert B Innis, M.D., Principal investigator, National Institute of Mental Health (NIMH)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07027839
- Sponsor's protocol ID
- 10002393
- Other IDs
- 002393-M
- Status last verified
- 26 Oct 2026
- First submitted
- 17 Jun 2025
- Last updated
- 2 Nov 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Acute Effects of Alcohol on PET Imaging of Phosphodiesterase-4B (PDE4B)
- ClinicalTrials.gov ID
- NCT07027839
- Acronym / sponsor ID
- 10002393
- Conditions
- Alcohol Use Disorder
- Keywords
- PET Imaging, Alcohol Use Disorder (AUD), Phosphodiesterase-4B (PDE4B)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- National Institute of Mental Health (NIMH)US National Institutes of Health
- Study start
- 11 Dec 2025 (actual)
- Primary completion
- 22 Feb 2028 (estimated)
- Study completion
- 22 Feb 2029 (estimated)
- First posted
- 19 Jun 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 following intravenous administration of ethanol to achieve a target breath alcohol concentration (BrAC) of 0.08 g% (80 mg/dL). For the ethanol condition, alcohol will be administered intravenously prior to PET acquisition to reach and stabilize the target BrAC. PET imaging will then be conducted without concurrent ethanol infusion. Participants from protocol 000676 will have already had the baseline scan with [18F]PF974 and will only undergo a single PET scan following intravenous ethanol
administration as described.
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 design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| One arm | Experimental | Drug: Intravenous Ethanol, Drug: 18F-PF-06445974All subjects will receive 18F-PF-06445974. In addition to 18F-PF-06445974 some subjects may receive ethanol infusion. |
Who may qualify
- Ages
- 21 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (15 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intravenous EthanolIntravenous ethanol infusion before PET Scan | Drug | One arm |
| 18F-PF-06445974Injected IV followed by PET scanning | Drug | One arm |
Primary outcome
To measure distribution volume
Time frame: 36 months
Target quantification
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Nov 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Robert B Innis, M.D. principal investigator
National Institute of Mental Health (NIMH)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Intravenous Ethanol and 18F-PF-06445974 in people with Alcohol Use Disorder, run by National Institute of Mental Health (NIMH) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 2 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Tara N Turon, C.R.N.P. ((301) 827-6599, tara.turon@nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To measure distribution volume (time frame: 36 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2026.