Spironolactone for Alcoholism

Overseen By Masoumeh Dejman

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Institute on Drug Abuse (NIDA)

Must not be taking: Diuretics, ARBs, ACEIs, others

Disqualifiers: Heart failure, Unstable cardiovascular, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 8 weeks

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test whether spironolactone, a medicine currently used for high blood pressure and heart failure, can help reduce alcohol intake in people who drink excessively. Researchers are evaluating how the body processes spironolactone and checking for any side effects when combined with alcohol. Participants will stay at a clinic for four separate weeks, taking either the medicine or a placebo (a harmless pill with no effect) without knowing which one they receive. This trial is suitable for adults with alcohol use disorder who often drink heavily, such as women consuming four or more drinks and men consuming five or more drinks on at least four days in the past month. As a Phase 1 trial, the research focuses on understanding how the treatment works in people.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, including diuretics, angiotensin receptor blockers, ACE inhibitors, potassium supplements, and some others. If you are on any of these, you would need to stop them to participate in the study.

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

Research shows that spironolactone may help reduce alcohol consumption. This medication, already used to treat high blood pressure and heart failure, provides some information about its safety. In these cases, spironolactone is usually well-tolerated. Common side effects include dizziness, headache, and stomach upset, but these are generally mild.

Animal studies suggest it can lower alcohol intake without causing serious side effects. However, since this trial is in the early stages, researchers are focusing on how spironolactone interacts with alcohol in humans and monitoring for any side effects. This trial aims to determine if spironolactone is safe and effective for treating alcohol use disorder (AUD). ^{1 2 3 4 5}

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

Unlike the standard treatments for alcoholism, which typically include medications like naltrexone, acamprosate, and disulfiram, spironolactone is being explored for its unique ability to modulate the body's aldosterone levels. Researchers are excited about spironolactone because it offers a novel approach by targeting the hormonal systems that might play a role in alcohol addiction. This could potentially provide a new avenue for treating alcoholism, especially for those who don't respond well to existing medications. By influencing the balance of certain hormones, spironolactone might help reduce cravings and withdrawal symptoms, making it a promising option in the fight against alcohol dependency.

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

Research has shown that spironolactone, which participants in this trial may receive, can help people with Alcohol Use Disorder (AUD) reduce their alcohol consumption. Studies found that those who took spironolactone reported drinking fewer alcoholic drinks each week compared to those who did not take it. On average, participants using spironolactone consumed about 3.5 fewer drinks per week. Additionally, various studies have linked this treatment to reduced alcohol use. These early results suggest that spironolactone could be a promising option for helping people with AUD drink less. ^{1 3 6 7 8}

Who Is on the Research Team?

Lorenzo Leggio, M.D.

Principal Investigator

National Institute on Drug Abuse (NIDA)

Are You a Good Fit for This Trial?

Adults aged 21+ with Alcohol Use Disorder who drink heavily are eligible for this trial. They must be in good general health, not pregnant or breastfeeding, and using effective birth control if applicable. Participants cannot have certain medical conditions like heart failure or unstable mental health issues, nor can they be on specific medications that could interfere with the study.

Inclusion Criteria

Self-reported drinking according to alcohol TimeLine Follow Back

Alcohol Use Disorder (minimum 2 symptoms on a validated diagnostic tool)

Most recent Clinical Institute Withdrawal Assessment for Alcohol revised (CIWA-Ar) score is < 10

Exclusion Criteria

I am currently taking medications such as water pills or blood pressure drugs.

Current use of certain pharmacotherapy for AUD, or seeking treatment for AUD

Pregnancy, intention to become pregnant, or breastfeeding

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo 4 separate 7-day stays at a clinic, taking spironolactone or placebo, with alcohol administration on day 6.

8 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Spironolactone

Trial Overview The trial is testing Spironolactone, a drug normally used for blood pressure and heart failure, to see if it helps people with AUD drink less alcohol. Participants will stay at a clinic multiple times taking either Spironolactone or a placebo without knowing which one they're getting. They'll also undergo tests and answer questions about their alcohol use.

How Is the Trial Designed?

Group I: Placebo 4th visit Experimental Treatment 2 Interventions

Stage1: 2x50 mg/day spironolactoneStage 2: 2x100 mg/day spironolactonestage 3: 2x200 mg/day spironolactonestage 4: Placebo

Group II: Placebo 3rd visit Experimental Treatment 2 Interventions

stage1: 2x50 mg/day spironolactonestage 2: 2x100 mg/day spironolactonestage 3: Placebostage4: 2x200 mg/day spironolactone

Group III: Placebo 2nd visit Experimental Treatment 2 Interventions

stage 1: 2x50 mg/day spironolactonestage 2: Placebostage3: 2x100 mg/day spironolactonestage 4: 2x200 mg/day spironolactone

Group IV: Placebo 1st visit Experimental Treatment 2 Interventions

stage 1: Placebostage 2: 2x50 mg/day spironolactonestage 3: 2x100 mg/day spironolactonestage4: 2x200 mg/day spironolactone

Spironolactone is already approved in United States, European Union for the following indications:

Approved in United States as Aldactone for:

• High blood pressure
• Heart failure
• Liver scarring
• Kidney disease
• Low blood potassium
• Early puberty in boys
• Acne
• Excessive hair growth in women

Approved in European Union as Aldactone for:

• Fluid retention due to heart failure
• Liver scarring
• Kidney disease
• High blood pressure
• Low blood potassium

Who Is Running the Clinical Trial?

National Institute on Drug Abuse (NIDA)

Lead Sponsor

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

Benzyl alcohol (BA), a preservative in triamcinolone acetonide (TA) suspensions, was found to be toxic to retinal pigment epithelial (RPE) cells in a dose- and time-dependent manner, with concentrations as low as 0.225 mg/mL causing significant damage after just 2 hours.

The study suggests that the use of commercial TA solutions containing BA for intravitreal injections can harm RPE cells, highlighting the need for preservative-free formulations to protect retinal health, especially during procedures like macular hole surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro benzyl alcohol cytotoxicity: implications for intravitreal use of triamcinolone acetonide. Chang, YS., Wu, CL., Tseng, SH., et al.[2013]

A study involving 523 adults treated with spironolactone for at least 90 days showed a significant reduction in weekly alcohol consumption, with treated patients reducing their intake by 3.50 drinks compared to 2.74 drinks in untreated patients, indicating spironolactone may be effective for alcohol use disorder (AUD).

Among heavy drinkers (those consuming more than 7 drinks per week), those treated with spironolactone experienced an even greater reduction of 4.18 drinks per week, suggesting that higher doses of spironolactone could lead to more significant improvements in alcohol consumption.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of spironolactone dispensation in reducing weekly alcohol use: a retrospective high-dimensional propensity score-matched cohort study. Palzes, VA., Farokhnia, M., Kline-Simon, AH., et al.[2022]

The glucocorticoid receptor antagonist mifepristone significantly reduced ethanol intake in rats under limited access conditions, with a maximum suppression of 40% at the highest dose (20 mg/kg).

In contrast, the mineralocorticoid receptor antagonist spironolactone did not affect ethanol consumption, highlighting the specific role of glucocorticoid receptors in regulating voluntary alcohol intake.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The glucocorticoid receptor antagonist mifepristone reduces ethanol intake in rats under limited access conditions. Koenig, HN., Olive, MF.[2013]

The study found that blocking the mineralocorticoid receptor (MR) with spironolactone significantly reduced alcohol self-administration in both male and female Long-Evans rats, indicating that MR signaling plays a role in alcohol consumption behaviors.

In female rats, spironolactone not only decreased alcohol intake but also reduced the persistence of seeking alcohol when it was no longer available, suggesting a stronger impact of MR antagonism on alcohol-related behaviors in females compared to males.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The mineralocorticoid receptor antagonist spironolactone reduces alcohol self-administration in female and male rats. Makhijani, VH., Van Voorhies, K., Besheer, J.[2019]

Intravitreal injection of 4 mg triamcinolone acetonide significantly improved visual acuity in diabetic patients with massive macular hard exudates, with improvements noted at multiple follow-up points over an average of 8.25 months.

The treatment led to complete resolution of hard exudates in 50% of cases and decreased fluorescein leakage, although 25% of patients experienced elevated intraocular pressure, which was manageable with topical medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Primary intravitreal triamcinolone acetonide for diabetic massive macular hard exudates. Khairallah, M., Zeghidi, H., Ladjimi, A., et al.[2022]

This study is the first to identify genetic variants that may predict treatment outcomes for alcohol use disorder (AUD) based on data from 1,083 participants, revealing that SNPs in the BRE gene are linked to relapse to heavy drinking.

Specific genetic markers were found to be associated with the effectiveness of naltrexone and acamprosate, suggesting that genetic testing could help tailor AUD treatments to individual patients for better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genetic contributions to alcohol use disorder treatment outcomes: a genome-wide pharmacogenomics study. Biernacka, JM., Coombes, BJ., Batzler, A., et al.[2022]

Intravitreal triamcinolone acetonide (TA) injections significantly improved vision in 56% of treated eyes after 2 years, compared to only 26% in the placebo group, indicating its efficacy in managing diabetic macular edema.

While TA treatment led to a higher incidence of increased intraocular pressure and cataract progression, these side effects were manageable, suggesting that the benefits of improved vision may outweigh the risks for patients with refractory diabetic macular edema.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravitreal triamcinolone for refractory diabetic macular edema: two-year results of a double-masked, placebo-controlled, randomized clinical trial. Gillies, MC., Sutter, FK., Simpson, JM., 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]

In a study of 16 patients with persistent serous choroidal detachment (SCD) after glaucoma surgery, a subtenon injection of triamcinolone acetonide (TA) led to complete resolution of SCD within 1 to 4 weeks.

The treatment was found to be safe, with no recurrence of SCD observed in any patient during the 6-month follow-up period, indicating its efficacy as a therapeutic option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subtenon triamcinolone injection to treat serous choroidal detachment after glaucoma surgery: A case series. Nilforushan, N., Abolfathzadeh, N., Najafzadeh, F., et al.[2023]

In a study of 22 patients with birdshot chorioretinopathy, implantation of a fluocinolone acetonide drug delivery device led to significant improvements in median visual acuity and complete resolution of vitreous haze in all eyes by 12 months.

While the treatment effectively controlled inflammation and reduced the need for systemic immunosuppressive therapy, it was associated with a high incidence of cataract progression and intraocular hypertension or glaucoma, necessitating additional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of birdshot chorioretinopathy treated with an intravitreal sustained-release fluocinolone acetonide-containing device. Rush, RB., Goldstein, DA., Callanan, DG., et al.[2022]

Acamprosate and naltrexone are effective pharmacotherapies for severe alcohol dependence, significantly reducing alcohol intake and increasing the chances of prolonged abstinence, supported by Level I evidence from multiple studies.

Acamprosate has shown sustained benefits over time and is well tolerated without known interactions with alcohol, while naltrexone can block opioid analgesics and requires adjunctive psychosocial treatment for optimal results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New pharmacotherapies for alcohol dependence. Graham, R., Wodak, AD., Whelan, G.[2020]

Allopregnanolone, a neuroactive steroid, shows promise as a therapeutic option for treating symptoms of alcohol use disorders (AUDs), supported by both basic science and clinical evidence.

The review highlights the importance of understanding how allopregnanolone and its precursor, pregnenolone, may help regulate stress and immune responses related to AUDs, while also addressing potential risks and management strategies for therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Rationale for Allopregnanolone Treatment of Alcohol Use Disorders: Basic and Clinical Studies. Morrow, AL., Boero, G., Porcu, P.[2021]

Citations

1. 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 ...

2. 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 ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05807139?term=Spironolactone&viewType=Table&rank=4

Spironolactone in Alcohol Use Disorder (SAUD) Researchers want to find better treatments for AUD. Animal studies found that a medicine called spironolactone , may decrease the amount of alcohol the animals ...

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

SPIRONOLACTONE THERAPY ASSOCIATES WITH ... Notably, AUD patients treated with spironolactone reported less alcohol use compared to those not receiving treatment (linear drinking score of ...

5. jci.org jci.org/articles/view/172889

Novel medications for problematic alcohol use The findings provided converging evidence that spironolactone prescription for any indication was associated with a reduction in alcohol use. ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05807139

Spironolactone in Alcohol Use Disorder (SAUD) Researchers want to find better treatments for AUD. Animal studies found that a medicine called spironolactone, may decrease the amount of alcohol the animals ...

7. niaaa.nih.gov niaaa.nih.gov/news-events/spectrum/volume-15-issue-1-winter-2023/heart-medication-shows-potential-treatment-alcohol-use-disorder

Heart Medication Shows Potential as Treatment for Alcohol ... In the present study, researchers showed, through experiments performed in mice and rats, that spironolactone decreases alcohol consumption.

8. cambridge.org cambridge.org/core/journals/european-psychiatry/article/spironolactone-in-alcohol-use-disorder-saud-introduction-to-an-ongoing-doubleblind-placebocontrolled-ascending-dose-phase-1b-study/0BCE7700B87E75C493BB660018234D49

Spironolactone in Alcohol Use Disorder (SAUD) The above-mentioned preclinical and clinical evidence suggest that spironolactone may be repurposed for the treatment of AUD. Our Phase 1b study ...