PET Imaging 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: Antidepressants, Antipsychotics

Disqualifiers: HIV, Pregnancy, Unstable medical condition, others

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

Compensation: Varies

Number of Visits: 2

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial requires that participants must not have taken antidepressants or antipsychotic medications in the week before or during their hospital stay. For other medications, the protocol does not specify, so it's best to discuss with the trial team.

Is PET imaging for alcoholism safe for humans?

PET imaging, which uses radiotracers to study brain function, has been used extensively in humans and is generally considered safe. The radiotracers used in PET scans are in very low concentrations and do not significantly affect the body's systems. ^{1 2 3 4 5}

How does PET imaging differ from other treatments for alcoholism?

PET imaging is unique because it uses a special type of scan to study the brain's activity and metabolism, helping to understand how alcohol affects the brain and to track changes during treatment. Unlike traditional treatments that focus on medication or therapy, PET imaging provides detailed insights into the brain's function, which can guide more personalized treatment strategies. ^{1 4 5 6 7}

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 adults aged 18 to 70 with Alcohol Use Disorder (AUD) who are already enrolled in protocol 14-AA-0181. They will undergo alcohol withdrawal in a clinic for about a month and participate in additional procedures to measure PDE4B levels.

Inclusion Criteria

Each participant must have a level of understanding sufficient to agree to all required tests and examinations and sign an informed consent document

Willingness to complete the study including MRI tests

Participants must have 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

Exclusion Criteria

Clinically significant abnormalities on laboratory testing beyond that expected in participants during alcohol withdrawal. This includes CBC and acute care panel (Na, K, Cl, CO2, creatinine, glucose, urea nitrogen)

I cannot lie flat or still for two hours due to physical or psychological reasons.

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Alcohol Withdrawal and Initial PET Scan

Participants undergo alcohol withdrawal and have an initial PET scan within the first week of admission

1 week

1 visit (in-patient)

Continued Alcohol Withdrawal and Second PET Scan

Participants continue alcohol withdrawal and have a second PET scan after 3-4 weeks

3-4 weeks

1 visit (in-patient)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• 18F-PF-06445974

Trial Overview The study tests if the protein PDE4B is at lower levels during AUD withdrawal and if it increases after abstaining from alcohol. Participants will have PET scans using an experimental tracer, 18F-PF-06445974, to visualize PDE4B, possibly along with MRI scans.

How Is the Trial Designed?

Group I: One-arm Experimental Treatment 1 Intervention

All subjects will receive the same tests.

Who Is Running the Clinical Trial?

National Institute of Mental Health (NIMH)

Lead Sponsor

Trials

3,007

Recruited

2,852,000+

Published Research Related to This Trial

Positron emission tomography (PET) studies have revealed that alcohol's rewarding effects are linked to changes in various neurotransmitter systems, including dopamine and GABA, as well as its caloric properties, which contribute to alcohol use disorders (AUD).

Research has shown that chronic alcohol exposure leads to significant alterations in brain metabolism and neurotransmitter function, which are associated with compulsive drinking and withdrawal symptoms, highlighting the potential for PET imaging to inform treatment strategies for AUD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurochemical and metabolic effects of acute and chronic alcohol in the human brain: Studies with positron emission tomography. Volkow, ND., Wiers, CE., Shokri-Kojori, E., et al.[2018]

In a study of 30 non-treatment-seeking alcoholics, aripiprazole (15 mg for 14 days) significantly reduced heavy drinking compared to a placebo, indicating its potential efficacy in promoting abstinence.

Brain imaging results showed that aripiprazole blunted activation in the right ventral striatum in response to alcohol cues, suggesting that it may alter the brain's response to alcohol-related stimuli.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of aripiprazole on cue-induced brain activation and drinking parameters in alcoholics. Myrick, H., Li, X., Randall, PK., et al.[2022]

Molecular imaging techniques like PET and SPECT have revealed that alcohol use disorder (AUD) is associated with significant changes in brain metabolism and neuroinflammation, particularly highlighting the role of GABA A-type receptors and the microglial marker translocator protein (TSPO).

Studies indicate that AUD patients show impaired dopamine synthesis and release, which may contribute to the disorder, while opioid receptor antagonists may help mitigate neuroinflammation, suggesting potential avenues for treatment development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular Imaging Studies of Alcohol Use Disorder. Bach, P., de Timary, P., Gründer, G., et al.[2023]

In a study of 25 patients with alcohol-related cognitive impairment (ARCI) and Wernicke encephalopathy (WE), significant brain hypometabolism was observed, particularly in the prefrontal medial cortex, prefrontal lateral cortex, and anterior cingulate cortex, indicating these areas are most affected by alcohol use disorder.

The study found that 72% of patients exhibited severe hypometabolism in the prefrontal medial cortex, suggesting that this brain region is crucial for understanding cognitive impairments related to alcohol use, and that the patterns of hypometabolism were similar between ARCI and WE patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain 18FDG-PET pattern in patients with alcohol-related cognitive impairment. Clergue-Duval, V., Questel, F., Azuar, J., et al.[2021]

Positron emission tomography (PET) is a highly sensitive imaging technology that can measure the concentration and distribution of radiotracers in the brain, allowing researchers to study neurochemical and metabolic processes without disrupting the system being measured.

PET has been effectively used to investigate the effects of alcohol and other drugs on brain function and neurochemistry in both humans and nonhuman primates, with new microPET technology enabling similar studies in rodents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Positron emission tomography as a tool for studying alcohol abuse. Thanos, PK., Wang, GJ., Volkow, ND.[2021]

In a study using [18F]-FDG microPET imaging on alcohol-drinking rats, it was found that alcohol significantly reduces overall brain glucose metabolism, particularly in the parietal cortex and cerebellum, indicating a direct impact of alcohol on brain function.

Long-term alcohol consumption leads to tolerance, as evidenced by diminished effects on glucose metabolism in long-term drinkers compared to alcohol-naïve and short-term drinkers, while some brain regions showed increased activity, suggesting complex changes in brain function during addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in cerebral [18F]-FDG uptake induced by acute alcohol administration in a rat model of alcoholism. Gispert, JD., Figueiras, FP., Vengeliene, V., et al.[2018]

Positron emission tomography (PET) is a powerful imaging technique that can detect early functional brain changes due to alcohol consumption, even before structural damage occurs.

Research using PET has shown that cognitive functions can gradually recover with continued abstinence from alcohol, and it has also provided insights into the mechanisms of alcohol's effects and the genetic factors related to alcoholism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monitoring the Brain's Response to Alcohol With Positron Emission Tomography. Volkow, N., Wang, GJ., Doria, JJ.[2020]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Neurochemical and metabolic effects of acute and chronic alcohol in the human brain: Studies with positron emission tomography. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

The effect of aripiprazole on cue-induced brain activation and drinking parameters in alcoholics. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

Molecular Imaging Studies of Alcohol Use Disorder. [2023]

4. Germany pubmed.ncbi.nlm.nih.gov

Brain 18FDG-PET pattern in patients with alcohol-related cognitive impairment. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Positron emission tomography as a tool for studying alcohol abuse. [2021]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Changes in cerebral [18F]-FDG uptake induced by acute alcohol administration in a rat model of alcoholism. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Monitoring the Brain's Response to Alcohol With Positron Emission Tomography. [2020]