Ethanol for Alcohol-Related Behaviors in Healthy Subjects

Overseen By Vijay A Ramchandani, Ph.D.

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Must not be taking: Antidepressants, Antihypertensives, Insulin, others

Disqualifiers: Major medical illness, Psychiatric disorders, Alcohol use disorder, Non-drinkers, others

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

Compensation: Varies

Number of Visits: 2

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand why some individuals might be more prone to alcohol use disorder (AUD) by studying a specific gene called ZIP8. Researchers will examine how different forms of this gene influence alcohol consumption and its effects on the brain. Participants will attend two visits, receive alcohol through an IV, and undergo brain scans. Healthy individuals of European ancestry who drink alcohol but do not have a history of alcohol-related issues are suitable for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a unique opportunity to contribute to groundbreaking genetic research.

Will I have to stop taking my current medications?

Yes, you may need to stop taking certain medications. The trial excludes participants using medications that interact with alcohol or affect alcohol metabolism, such as some heart, diabetes, and pain medications. You must refrain from these medications for a specified period before the study.

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

Research has shown that receiving alcohol directly into the bloodstream through an IV affects the body in several ways. Some studies suggest it might slightly increase heart rate, body temperature, and blood pressure. Other reports mention it can cause feelings of restlessness and mood changes. These effects occur more often in people who have recently consumed alcohol.

It's important to remember that alcohol is widely used, and its effects are generally well-known. However, receiving it through an IV may feel different than drinking it. Participants in such trials are closely monitored to ensure their safety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike other treatments for alcohol-related behaviors, which typically focus on behavioral therapies and medications like naltrexone or acamprosate, ZIP8 involves the use of IV ethanol. This approach is unique because it directly administers ethanol, the substance involved in alcohol use, in a controlled setting to understand its effects on behavior. Researchers are excited about this treatment because it could offer new insights into how alcohol influences behavior, potentially leading to innovative strategies for managing alcohol-related conditions.

What evidence suggests that this trial's treatments could be effective for understanding alcohol-related behaviors?

Research has shown that administering alcohol through an IV can mimic the effects of drinking alcohol, but in a controlled setting. In studies, participants reported that small amounts of IV alcohol felt like consuming just over one drink, while larger amounts felt like almost two drinks. This method allows researchers to study alcohol's impact on the brain and behavior without requiring participants to drink. In this trial, researchers also examine the ZIP8 gene to determine how genetic differences might influence alcohol use and its effects on the brain. The primary goal of this research is to understand these effects, not to test treatments. ^{2 5 6 7 8}

Who Is on the Research Team?

Vijay A Ramchandani, Ph.D.

Principal Investigator

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Are You a Good Fit for This Trial?

This trial is for healthy individuals aged 21 to 60 with European ancestry who don't smoke and have no history of alcohol use disorder. They must be part of another study (14-AA-0181) and cannot have any conditions that exclude them from safely participating.

Inclusion Criteria

I am between 21 and 60 years old.

Non-smokers with no history of smoking in the past year and not a daily smoker for more than 1 month in their lifetime

Participants of European ancestry

Exclusion Criteria

Current history of psychiatric disorders, including depressive disorder, bipolar disorder, or anxiety disorders

Lifetime history of psychotic disorders, obsessive compulsive disorder (OCD), posttraumatic stress disorder (PTSD), or eating disorder

Current or lifetime diagnosis of alcohol or substance use disorder

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Alcohol Infusion and Self-Administration

Participants receive alcohol infusion and may self-administer doses by pressing a button during a 2.5-hour session. Blood samples and breath measurements are taken, and participants complete computer tasks and questionnaires.

1 day

1 visit (in-person)

Imaging and Cognitive Tasks

Participants undergo an imaging scan of their brain and perform tasks and games on a computer screen during the scan.

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the main study visits.

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ZIP8

Trial Overview

The study investigates how different forms of the ZIP8 gene influence drinking behavior and brain response to alcohol in healthy people. Participants will receive alcohol intravenously, perform computer tasks, answer questionnaires, and undergo a brain imaging scan.

How Is the Trial Designed?

Group I: IV Ethanol Experimental Treatment 1 Intervention

IV Ethanol

Who Is Running the Clinical Trial?

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Lead Sponsor

Trials

865

Recruited

1,091,000+

Published Research Related to This Trial

Alcohol Use Disorder (AUD) affects over 76 million people globally, and current FDA-approved treatments are largely ineffective, highlighting the need for new therapeutic options.

The study employs two rodent drinking models—two-bottle choice (TBC) and drinking in the dark (DID)—to evaluate the effectiveness of new anti-alcohol compounds, providing a rapid and efficient way to screen potential treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Murine Drinking Models in the Development of Pharmacotherapies for Alcoholism: Drinking in the Dark and Two-bottle Choice. Huynh, N., Arabian, NM., Asatryan, L., et al.[2022]

The benzodiazepine partial inverse agonist RO19-4603 significantly reduced ethanol (EtOH) intake in alcohol-preferring rats, with effective doses as low as 0.009 mg/kg, demonstrating both immediate and prolonged effects on drinking behavior over two days.

The study suggests that RO19-4603 may offer a potential therapeutic approach for reducing alcohol consumption, as it selectively decreased EtOH intake without affecting saccharin or food intake, indicating a targeted effect on alcohol reinforcement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of the benzodiazepine inverse agonist RO19-4603 alone and in combination with the benzodiazepine receptor antagonists flumazenil, ZK 93426 and CGS 8216, on ethanol intake in alcohol-preferring (P) rats. June, HL., Greene, TL., Murphy, JM., et al.[2017]

Citations

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An Evaluation of Intravenous Ethanol in Hospitalized Patients

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