Alcohol for Alcoholism

Overseen By Robert B Innis, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Institute of Mental Health (NIMH)

Must not be taking: Antipsychotics, Antidepressants, Benzodiazepines, Opioids

Disqualifiers: AUD, SUD, HIV, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if alcohol consumption increases the activity of a specific brain protein, Phosphodiesterase-4B (PDE4B), potentially leading to new treatments for alcohol use disorder (AUD). Participants will undergo brain imaging (PET Imaging of Phosphodiesterase-4B) to observe changes in PDE4B activity with alcohol intake. Healthy individuals who drink socially, do not have AUD, and are already part of a related study qualify for participation. Participants will undergo brain scans both with and without alcohol in their system to provide baseline and comparative data. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants a unique opportunity to contribute to groundbreaking scientific discovery.

Will I have to stop taking my current medications?

Yes, you may need to stop taking certain medications. If you are on antipsychotics, antidepressants, or medications that interact with alcohol, you might need to stop them for a specific period before the trial. Check with the trial team for details on your specific medications.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that PET imaging of a protein called Phosphodiesterase-4B (PDE4B) has been studied in animals, exploring how alcohol affects this protein in the brain. The imaging uses a special radioactive tracer to highlight the protein's activity. Tests in animal brains have revealed how alcohol changes the protein's behavior.

This trial is in an early stage regarding safety in humans. Researchers are still determining safe doses and checking for possible side effects. The radioactive tracer used is common in PET scans, which are widely used in medicine. While this doesn't guarantee safety, it suggests the procedure is generally considered low-risk.

Participants in this study will undergo a PET scan before and after receiving alcohol through an IV. They will also have an MRI scan. These imaging methods are non-invasive and usually well-tolerated. However, the effects of combining the tracer with alcohol in humans are still under study. Participants receive close monitoring for any side effects during and after the procedure. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for alcoholism focus on behavioral therapy or medications that affect neurotransmitters, like naltrexone, acamprosate, or disulfiram. But this new approach uses PET imaging of Phosphodiesterase-4B (PDE4B) with a compound called 18F-PF-06445974. Researchers are excited because this method could provide a unique insight into brain activity linked to alcoholism by directly targeting PDE4B, which plays a role in inflammation and mood regulation. This could lead to more personalized treatments by understanding how alcohol affects brain chemistry in real time.

What evidence suggests that this trial's treatment could be effective for increasing PDE4B activity in the brain?

Research has shown that alcohol might increase the activity of a protein in the brain called Phosphodiesterase-4B (PDE4B). An earlier study found that alcohol exposure quickly increased the attachment of a tracer to this protein in rat brains, indicating heightened activity. This type of imaging helps scientists understand how alcohol might alter brain chemistry. In this trial, all subjects will receive 18F-PF-06445974, and some may also receive an ethanol infusion to further investigate these effects. By learning more about this, researchers aim to develop better treatments for alcohol use disorder (AUD). While animal studies have shown promise, more research is needed to determine if the same effects occur in humans. ^{1 6 7 8 9}

Who Is on the Research Team?

Robert B Innis, M.D.

Principal Investigator

National Institute of Mental Health (NIMH)

Are You a Good Fit for This Trial?

This trial is for healthy adults aged 21 to 70 who drink socially but don't have Alcohol Use Disorder. They must already be part of the NIAAA Natural History Protocol study. The trial aims to understand alcohol's effect on a brain protein in social drinkers.

Inclusion Criteria

I am between 21 and 70 years old.

Enrolled in protocol 14-AA-0181, NIAAA Natural History Protocol

Willingness to complete the study including MRI tests

Exclusion Criteria

Inability to have an MRI scan

I am HIV positive.

History of AUD or SUD

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline PET Scan

Participants undergo a baseline PET scan with a radioactive tracer to measure PDE4B binding in the brain

1 day

1 visit (in-person)

Ethanol Infusion PET Scan

Participants receive an ethanol infusion to reach a target blood alcohol concentration and undergo a PET scan to measure changes in PDE4B binding

1 day

1 visit (in-person)

MRI Scan

Participants undergo an MRI scan of the brain

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the imaging procedures

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• PET Imaging of Phosphodiesterase-4B (PDE4B)

Trial Overview The study tests how alcohol affects PDE4B activity in the brain using PET scans with a radioactive tracer, before and after administering intravenous ethanol (alcohol). Participants will also undergo an MRI scan during one of their clinic visits.

How Is the Trial Designed?

Group I: One arm Experimental Treatment 2 Interventions

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

Who Is Running the Clinical Trial?

National Institute of Mental Health (NIMH)

Lead Sponsor

Trials

3,007

Recruited

2,852,000+

Citations

1. nature.com nature.com/articles/s41386-024-01988-y

PET imaging in rat brain shows opposite effects of acute ... This study found that acute alcohol exposure rapidly increased PDE4B radioligand binding in rat brains as early as 0.5 hours post-exposure, an ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT07027839

NCT07027839 | Acute Effects of Alcohol on PET Imaging ... 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 ...

3. jnm.snmjournals.org jnm.snmjournals.org/content/64/supplement_1/p255

In vivo assessment of brain cyclic adenosine monophosphate ... The objective of this study is to estimate the brain level of PDE4B in a rat model of chronic alcohol exposure using PET imaging.

4. trial.medpath.com trial.medpath.com/clinical-trial/bfd0c8ff29c7e292/nct06795581-pet-imaging-pde4b-alcohol-use-disorder

PET Imaging of Phosphodiesterase-4B (PDE4B) in Alcohol ... What is the comparative efficacy of PDE4B imaging versus other biomarkers in predicting AUD treatment outcomes? Which biomarkers predict response to PDE4B ...

5. biologicalpsychiatryjournal.com biologicalpsychiatryjournal.com/article/S0006-3223(24)00355-X/fulltext

19. Radioligand Binding to Phosphodiesterase-4B, a ... After chronic alcohol exposure, widespread reduction of PDE4B binding was detected at 5 hours post-exposure. PDE4B binding was normalized at 3 ...

6. jnm.snmjournals.org jnm.snmjournals.org/content/65/supplement_2/241130

PET Imaging of Phosphodiesterase-4B as an Indirect ... This study assessed the effect of acute and chronic alcohol administration on PDE4B in rat brain using positron emission tomography (PET) as an indirect ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39285225/

PET imaging in rat brain shows opposite effects of acute and ... PET imaging in rat brain shows opposite effects of acute and chronic alcohol exposure on phosphodiesterase-4B, an indirect biomarker of cAMP ...

8. trialx.com trialx.com/clinical-trials/listings/300858/pet-imaging-of-phosphodiesterase-4b-pde4b-in-alcohol-use-disorder/

PET Imaging of Phosphodiesterase-4B (PDE4B) in Alcohol ... Using the PET radioligand [18F]PF974 to measure the density of PDE4B, AUD participants will be scanned twice: 1) within one week of admission, ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT07169630

PET Imaging of Phosphodiesterase-4 (PDE4) in Volunteers ... Participants must not have substance use disorder or alcohol use disorder. Participants should not be under treatment or previously treated with an amyloid ...