Varenicline for Alcoholism

(HARP Trial)

Overseen By June-Marie Weiss, MA, MEd

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Yale University

Must not be taking: Alcohol treatment medications

Disqualifiers: Pregnancy, Opioid use disorder, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 12 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if the medication varenicline can reduce alcohol use in individuals with both HIV and alcohol use disorder (AUD). Participants will receive a prescription for varenicline to test its effectiveness for this purpose. The trial seeks individuals who have HIV, receive care at the Atlanta VA Healthcare System, and currently smoke cigarettes. Participants should also have significant alcohol use and be prescribed five or more medications. This trial excludes those already in formal alcohol treatment or with certain medical conditions.

As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking medications that interact with the study drug, like nicotine replacement therapy.

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

Research has shown that varenicline is generally well-tolerated and can significantly reduce alcohol consumption. Specifically, individuals taking varenicline experienced 33% fewer days of heavy drinking compared to those not taking it.

Regarding safety, previous studies have found varenicline safe to use, though it may cause mild side effects like nausea and trouble sleeping, which usually subside over time.

It's important to note that while this study is in an early phase, the FDA has already approved varenicline to help people quit smoking, indicating it has undergone safety testing in humans. Although its use for reducing alcohol consumption is new, the existing safety data is encouraging. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for alcoholism?

Most treatments for alcoholism, such as naltrexone and acamprosate, work by reducing cravings or mitigating withdrawal symptoms. But varenicline works differently, targeting the brain's reward system by acting on nicotine receptors, which may reduce the pleasure associated with alcohol consumption. Researchers are excited about varenicline because it offers a novel approach that could potentially address both smoking and alcohol use disorders, broadening its impact. This dual-action mechanism might provide a more comprehensive treatment option for individuals struggling with both addictions, setting it apart from current options.

What evidence suggests that varenicline might be an effective treatment for alcohol use disorder?

Research has shown that varenicline, which participants in this trial will receive, can help reduce alcohol consumption and cravings. One study found that individuals with alcohol use disorder (AUD) who took varenicline experienced fewer heavy drinking days. Another study demonstrated that varenicline significantly reduced both alcohol use and cravings compared to a placebo. However, not all studies fully agree; some suggest it reduces cravings but does not always lead to less drinking overall. Overall, these findings suggest varenicline might be a helpful option for treating AUD. ^{1 3 4 6 7}

Who Is on the Research Team?

E. Jennifer Edelman, MD, MHS

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for adults over 18 with HIV and moderate to severe alcohol use disorder, receiving care at the Atlanta VA Healthcare System. Participants must be current smokers, on multiple medications, have a high level of recent alcohol use indicated by PEth test, and able to consent. Pregnant or nursing individuals, those with life-threatening conditions or untreated opioid disorders are excluded.

Inclusion Criteria

Receive care at the Atlanta VA Healthcare System

Meet criteria for moderate to severe alcohol use disorder by the DSM-5 Alcohol Symptom Checklist

Can provide written informed consent

Exclusion Criteria

History of serious hypersensitivity or adverse reaction to study medication

Self-report or laboratory test confirming pregnancy, nursing, or trying to conceive

Untreated moderate to severe opioid use disorder

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive a 12-week intervention including off-label use of medication with medical management and a clinical pharmacist-delivered behavioral intervention

12 weeks

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Varenicline

Trial Overview The study tests Varenicline's off-label effectiveness in reducing alcohol consumption among HIV patients with AUD. It combines medication with medical management and behavioral interventions delivered by a clinical pharmacist.

How Is the Trial Designed?

Group I: Varenicline Experimental Treatment 1 Intervention

Participants will receive a prescription for generic varenicline

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Collaborator

Trials

865

Recruited

1,091,000+

Published Research Related to This Trial

Varenicline is an effective treatment for nicotine addiction, promoting abstinence safely in most patients, but there are reports of neuropsychiatric adverse events in a small number of cases.

Veterans, who often have higher rates of psychiatric conditions and nicotine dependence, may be at increased risk for serious side effects from varenicline, highlighting the need for close monitoring in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse neuropsychiatric events associated with varenicline use in veterans: a case series. Cantrell, M., Argo, T., Haak, L., et al.[2015]

Varenicline has been shown to effectively reduce alcohol cravings and overall alcohol consumption in patients with alcohol use disorders, based on data from 7 randomized, placebo-controlled trials and 1 open-label study.

While varenicline helps decrease drinking behavior, it does not significantly improve the rates of abstinence from alcohol, indicating its role may be more about managing cravings rather than achieving complete sobriety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Varenicline in the treatment of alcohol use disorders. Erwin, BL., Slaton, RM.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10001935/

Efficacy of Varenicline in the Treatment of Alcohol Dependence Conclusion: Our results indicated that AD patients treated with varenicline showed improvement in percentage of very heavy drinking days, percentage of ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3914416/

A Double-Blind, Placebo-Controlled Trial Assessing the ... Varenicline significantly reduced alcohol consumption and craving, making it a potentially viable option for the treatment of alcohol use disorders.

3. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2794965

Effectiveness of Varenicline and Cytisine for Alcohol Use ... Studies among smokers who drink alcohol demonstrate that varenicline reduces alcohol craving and consumption compared with placebo. Cytisine, a ...

4. thelancet.com thelancet.com/journals/lanepe/article/PIIS2666-7762(25)00102-4/fulltext

Efficacy and safety of varenicline and bupropion, in ... This study confirms animal data, and is the first to translate this beneficial effect of combined varenicline and bupropion on alcohol intake to ...

5. healio.com healio.com/news/psychiatry/20200304/varenicline-curbs-alcohol-craving-but-fails-to-improve-drinkingrelated-outcomes

Varenicline curbs alcohol craving but fails to improve ... Varenicline appeared to reduce alcohol craving among individuals with alcohol use disorders, but it did not improve drinking-related outcomes.

6. niaaa.nih.gov niaaa.nih.gov/research/data-archive-resources/niaaa-controlled-datasets/varenicline-study

Varenicline Study Data Access The varenicline group had significantly lower weekly percent heavy drinking days (primary outcome) (adjusted mean difference = 10.4), drinks per day, drinks per ...

7. psychiatryonline.org psychiatryonline.org/doi/10.1176/appi.pn.2015.6b17

Varenicline Shows Promise for Reducing Alcohol Use The results showed that participants taking varenicline had an average of 33 percent fewer heavy drinking days over the course of the trial compared with the ...