Spironolactone for Alcoholism in HIV Patients

(HARP Trial)

Overseen By June-Marie Weiss, MA, MEd

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Yale University

Must not be taking: Eplerenone, Potassium, Lithium, others

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: Unknown

Duration: 12 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to assist people with HIV who also struggle with alcohol use. Researchers aim to determine if spironolactone, a diuretic commonly used for heart failure and high blood pressure, can reduce alcohol consumption when combined with medical management and behavioral support. Participants must have HIV, receive care at the Atlanta VA, and currently consume a significant amount of alcohol. This study may suit individuals with HIV who are not in formal alcohol treatment but wish to reduce their drinking. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I have to stop taking my current medications to join the trial?

The trial does not specify if you must stop taking your current medications, but you cannot participate if you are taking certain medications that interact with spironolactone, such as eplerenone, potassium supplements, lithium, digoxin, cholestyramine, and heparin.

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

Research has shown that spironolactone is generally safe for people. The FDA has already approved it for treating heart problems and high blood pressure, providing extensive safety information for these uses.

In studies on alcohol use disorder, participants who took spironolactone consumed less alcohol, and no serious side effects were reported.

Overall, spironolactone seems to be a safe option for those considering joining this trial, with a strong track record in treating other health issues. ^{1 2 3 4 5}

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

Most treatments for alcohol use disorder in patients with HIV focus on behavioral therapies or medications like naltrexone, acamprosate, and disulfiram. But spironolactone works differently, targeting the mineralocorticoid receptor, which may help reduce alcohol cravings. Researchers are excited about spironolactone because it offers a unique approach by potentially addressing both alcohol use disorder and the inflammatory effects of HIV. This dual action could provide a more comprehensive treatment option for patients managing both conditions.

What evidence suggests that spironolactone might be an effective treatment for alcoholism in HIV patients?

Research has shown that spironolactone, which participants in this trial will receive, might help people with alcohol use disorder (AUD) reduce their alcohol consumption. Studies have found that those taking spironolactone drank fewer alcoholic drinks each week compared to those not taking the medication. Specifically, one study showed that participants taking spironolactone reduced their alcohol use by an average of 3.5 drinks per week. Evidence also suggests that higher doses of spironolactone might lead to even greater reductions in alcohol use. This indicates that spironolactone could be a promising treatment for helping people with AUD, including those with HIV, to drink less alcohol. ^{1 2 5 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, who are patients at the Atlanta VA Healthcare System. They must have significant alcohol use indicated by specific tests, be on multiple medications, and able to give informed consent.

Inclusion Criteria

Receives care at the Atlanta VA Healthcare System

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

Scores >7 on the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) screen

Exclusion Criteria

I do not have any severe health or mental conditions that would stop me from participating.

Has an inability to read or understand English

Has a history of serious hypersensitivity or adverse reaction to study medication

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

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

12 weeks

Regular study visits for counseling and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Off-Label Medications for Alcohol Use Disorder Among Patients With HIV: Pilot Study 1

Trial Overview The study is testing Spironolactone as an off-label treatment for reducing alcohol consumption in individuals with HIV and AUD. It includes medical management and a behavioral intervention delivered by a clinical pharmacist.

How Is the Trial Designed?

Group I: Spironolactone Experimental Treatment 1 Intervention

Participants will receive a prescription for spironolactone

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

Among individuals diagnosed with alcohol use disorder, only 1.0% of people living with HIV (PLWH) and 0.14% were retained on medications for alcohol use disorder (MAUD), indicating a significant treatment gap.

PLWH were less likely to initiate MAUD compared to uninfected individuals, with factors like older age and being black associated with lower odds of starting treatment, highlighting the need for targeted strategies to improve access and retention in these populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of initiation of and retention on medications for alcohol use disorder among people living with and without HIV. Oldfield, BJ., McGinnis, KA., Edelman, EJ., et al.[2021]

In a randomized clinical trial involving 194 women living with HIV, daily oral naltrexone (50 mg) showed a greater reduction in alcohol consumption at 1 and 3 months compared to placebo, although the overall reduction in drinking at 4 and 7 months was similar between both groups.

Women who reduced or quit drinking had significantly better HIV viral suppression rates at 4 months (72% vs. 53%) and 7 months (74% vs. 54%), highlighting the importance of reducing unhealthy alcohol use for improving health outcomes in women living with HIV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduction in Drinking was Associated With Improved Clinical Outcomes in Women With HIV Infection and Unhealthy Alcohol Use: Results From a Randomized Clinical Trial of Oral Naltrexone Versus Placebo. Cook, RL., Zhou, Z., Miguez, MJ., et al.[2020]

A pilot study involving 17 women living with HIV/AIDS showed that both naltrexone and placebo led to significant reductions in alcohol consumption, from an average of 39.2 drinks per week to 12.8 drinks per week over 4 months.

The study demonstrated that a pharmacologic intervention for reducing alcohol consumption is feasible and acceptable in this population, although recruitment challenges were noted that need to be addressed for future trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acceptability and feasibility of a randomized clinical trial of oral naltrexone vs. placebo for women living with HIV infection: Study design challenges and pilot study results. Cook, RL., Weber, KM., Mai, D., et al.[2022]

In both mouse and rat models, spironolactone significantly reduced alcohol consumption without affecting the intake of non-alcoholic sweet solutions or other behaviors, indicating its specific action on alcohol use.

In a human study, individuals taking spironolactone for at least 60 days reported a greater reduction in alcohol consumption, especially among those with higher baseline alcohol use, suggesting its potential as a novel treatment for alcohol use disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spironolactone as a potential new pharmacotherapy for alcohol use disorder: convergent evidence from rodent and human studies. Farokhnia, M., Rentsch, CT., Chuong, V., et al.[2023]

The NOAH Study, involving 365 participants predominantly male and African American, aims to investigate the adverse health outcomes of alcohol use in people living with HIV, building on preclinical findings from rhesus macaque models.

Baseline results show that while 12.8% of participants had low CD4 counts and 73.6% had undetectable viral loads, these HIV status indicators did not vary with alcohol use, suggesting a complex relationship between alcohol consumption and HIV health outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The New Orleans Alcohol Use in HIV Study: Launching a Translational Investigation of the Interaction of Alcohol Use with Biological and Socioenvironmental Risk Factors for Multimorbidity in People Living with HIV. Welsh, DA., Ferguson, T., Theall, KP., et al.[2021]

Citations

1. withpower.com withpower.com/trial/phase-alcoholism-9-2023-37b4d

Spironolactone for Alcoholism in HIV Patients (HARP Trial) Among individuals diagnosed with alcohol use disorder, only 1.0% of people living with HIV (PLWH) and 0.14% were retained on medications for alcohol use ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10231646/

Spironolactone as a potential new pharmacotherapy for ... Results showed a greater reduction in alcohol drinking among individuals who received spironolactone than those who did not. A significant dose ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8505557/

Effectiveness of spironolactone dispensation in reducing ... On average, spironolactone-treated patients reduced alcohol use by 3.50 drinks/week (95% CI = −4.22, −2.79), while untreated patients reduced ...

4. researchonline.lshtm.ac.uk researchonline.lshtm.ac.uk/id/eprint/4667528/1/Farokhnia_etal_2022_Spironolactone-as-a-potential-new.pdf

1 Spironolactone as a Potential New Pharmacotherapy for ... Results showed a greater reduction in alcohol drinking among individuals who received spironolactone than those who did not. A significant dose- response ...

5. aasld.org aasld.org/the-liver-meeting/spironolactone-therapy-associates-reduced-incident-alcohol-associated-liver

SPIRONOLACTONE THERAPY ASSOCIATES WITH ... Conclusion: Spironolactone therapy is associated with reduced alcohol use and incident ALD in patients with AUD and may offer a novel ...

6. medicalnewstoday.com medicalnewstoday.com/articles/drugs-spironolactone-oral-tablet

Spironolactone oral tablet: Dosage, side effects, uses, and ... Spironolactone oral tablets are FDA-approved to treat heart failure with reduced ejection fraction, edema in people with certain kidney and liver problems, ...

7. go.drugbank.com go.drugbank.com/drugs/DB00421

Spironolactone: Uses, Interactions, Mechanism of Action Spironolactone is an aldosterone receptor antagonist used to treat edema, hypertension, heart failure, and aldosteronism.