Doxazosin for Alcohol Use Disorder

(DOXY Trial)

Overseen By Zoe L Brown, BA

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Brown University

Must not be taking: Alpha-blockers, PDE5 inhibitors

Disqualifiers: Pregnancy, Substance disorder, CHF, others

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

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

184 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

You may need to stop taking certain medications if they interact with doxazosin or yohimbine, or if you are currently using medications like disulfiram, naltrexone, acamprosate, topiramate, or any alpha-blocker. The trial does not specify a washout period, but these medications should not be used within one month prior to screening.

Is Doxazosin safe for humans?

Doxazosin has been studied for various conditions and is generally considered safe for human use, but specific safety data for its use in treating alcohol use disorder is not detailed in the provided research. ^{1 2 3 4 5}

How is the drug doxazosin unique in treating alcohol use disorder?

Doxazosin is unique because it targets the norepinephrine system, which is a new approach for treating alcohol dependence. It has a longer half-life than similar drugs like prazosin, potentially making it more effective for reducing alcohol intake, especially in individuals with a family history of alcoholism. ^{6 7 8 9 10}

What is the purpose of this trial?

The goal of this research is to replicate findings previously conducted in a pilot trial and to understand, mechanistically, the role of stress in the development of AUD pharmacotherapies that target noradrenergic blockade.

Research Team

Carolina L Haass-Koffler, PHARMD, PHD

Principal Investigator

Brown University

Eligibility Criteria

This trial is for men and women aged 18-70 who have been diagnosed with Alcohol Use Disorder (AUD) according to DSM-5, want to cut down or stop drinking alcohol, are in good health based on medical checks, and can understand English at an 8th grade level. Pregnant or breastfeeding women, individuals with certain health conditions like kidney problems or heart failure, those who've attempted suicide recently, or people taking conflicting medications cannot participate.

Inclusion Criteria

In good health as confirmed by medical history, physical examination and lab tests

Understand informed consent and questionnaires in English at an 8th grade level

Desire to reduce or quit alcohol drinking

Exclusion Criteria

I have been diagnosed with heart failure.

Clinical Institute Withdrawal Assessment for Alcohol revised (CIWA-Ar) score ≥ 8

Current diagnosis of other substance disorder other than nicotine as assessed by self-report and urine toxicology screen at baseline

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive doxazosin (16 mg, or maximum tolerated dose) or placebo in a double-blind, randomized manner

16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Doxazosin
• Placebo

Trial Overview The study is testing the effectiveness of Doxazosin (an alpha-1 blocker) compared to a placebo in treating AUD. It aims to confirm previous pilot results and explore how stress affects the development of treatments that target specific nervous system pathways involved in AUD.

Participant Groups

Group I: doxazosin Experimental Treatment 1 Intervention

16 mg, or maximum tolerated dose (MTD)

Group II: placebo Placebo Group 1 Intervention

matching placebo

Doxazosin is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Cardura for:

• Benign prostatic hyperplasia
• Hypertension

Approved in United States as Cardura for:

• Benign prostatic hyperplasia
• Hypertension

Approved in Canada as Cardura for:

• Benign prostatic hyperplasia
• Hypertension

Approved in Japan as Carduran for:

• Benign prostatic hyperplasia
• Hypertension

Who Is Running the Clinical Trial?

Brown University

Lead Sponsor

Trials

480

Recruited

724,000+

Findings from Research

Among women veterans diagnosed with alcohol use disorder (AUD), those involved in the criminal justice system had higher odds (29% more likely) of receiving pharmacotherapy for AUD compared to those without justice involvement, indicating that legal mandates and supportive programs may facilitate access to treatment.

Despite the overall increase in pharmacotherapy receipt among women veterans from 14% to 21% between 2014 and 2017, older women (55+) and African-American veterans had lower odds of receiving treatment, highlighting disparities in access to AUD pharmacotherapy within this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Receipt of pharmacotherapy for alcohol use disorder by justice-involved women in the Veterans Health Administration. Taylor, E., Timko, C., Harris, AHS., et al.[2021]

In a study of 49 veterans prescribed pioglitazone for diabetes, the Alcohol Use Disorder Identification Test-Consumption (AUDIT-C) scores significantly decreased from an average of 3.98 to 2.89, indicating reduced alcohol consumption after starting the medication.

This study is the first to suggest that pioglitazone may effectively reduce alcohol use in patients with heavy drinking, highlighting the need for further clinical trials to explore its potential as a treatment for alcohol use disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced alcohol use in patients prescribed pioglitazone. Dieperink, E., Hauser, P., Dockter, K., et al.[2021]

A retrospective review of six individuals on therapeutic anticoagulation who received extended-release naltrexone (XR-NTX) for alcohol use disorder found no documented complications, suggesting that XR-NTX may be safely tolerated in this population.

The study highlights the need for larger research to evaluate the safety and efficacy of XR-NTX in patients on anticoagulation and those with coagulopathies, to better inform treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended-release naltrexone for people with alcohol use disorder on therapeutic anticoagulation: A case series. Ciraldo, K., Seraydarian, M., Gasper, J., et al.[2022]

Pharmacological treatments for alcohol use disorders (AUD), such as acamprosate, naltrexone, nalmefene, and disulfiram, are effective but underused, highlighting the need for better implementation despite their proven efficacy.

Each medication has a distinct safety profile that must be carefully considered alongside individual patient circumstances, including their drinking patterns and any comorbid conditions, to optimize treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Tolerability of Pharmacological Treatment of Alcohol Dependence: Comprehensive Review of Evidence. Sinclair, JM., Chambers, SE., Shiles, CJ., et al.[2018]

Alcohol use disorder (AUD) is common but often under-treated, with only three approved medications, highlighting the need for more diverse and effective treatment options.

The review discusses various pharmacotherapies, including both approved and novel agents, showing promise for improving treatment efficacy and supporting personalized medicine approaches for individuals with AUD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel Agents for the Pharmacological Treatment of Alcohol Use Disorder. Burnette, EM., Nieto, SJ., Grodin, EN., et al.[2022]

Doxazosin, an alpha 1 receptor antagonist, significantly reduced voluntary ethanol intake in mice, regardless of their history of alcohol dependence or stress exposure, indicating its potential as an effective treatment for alcohol use disorder.

Zonisamide, a novel anticonvulsant, showed a modest effect on reducing ethanol intake and may require longer treatment durations to be more effective, but combining it with doxazosin did not enhance the results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the effect of doxasozin and zonisamide on voluntary ethanol intake in mice that experienced chronic intermittent ethanol exposure and stress. Lopez, MF., Reasons, SE., Carper, BA., et al.[2023]

Doxazosin mesylate (Cardura) offers therapeutic advantages such as once-daily dosing, making it a convenient option for patients compared to other antihypertensive medications.

The evaluation was conducted at the Veterans Administration Lakeside Medical Center, which serves over 12,000 veterans, highlighting the potential for doxazosin to be a cost-effective alternative in managing hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, efficacy, and lipid profile of doxazosin at a VA medical center. Boston, D., Collins, C.[2013]

In a 12-week study involving 141 military veterans, doxazosin was found to be safe and well-tolerated, with no significant differences in reducing PTSD or alcohol use disorder severity compared to placebo.

While doxazosin led to a higher rate of abstinence during treatment (22% vs 7% for placebo), participants in the doxazosin group reported consuming more drinks on drinking days, indicating that it did not effectively reduce overall alcohol consumption.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Double-Blind Randomized Controlled Trial of Doxazosin for Co-Occurring PTSD and Alcohol Use Disorder in Veterans. Back, SE., Flanagan, JC., Mintz, J., et al.[2023]

In a clinical trial involving 41 individuals with alcohol dependence, doxazosin did not show overall effectiveness in reducing alcohol consumption compared to placebo, but it had significant effects based on family history of alcoholism.

Doxazosin significantly reduced drinking in patients with a high family history density of alcoholism, suggesting that it may be a promising treatment option for a specific subgroup of alcohol-dependent individuals, highlighting the potential for personalized medicine in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of the α1 blocker doxazosin in alcoholism: a proof-of-concept randomized controlled trial. Kenna, GA., Haass-Koffler, CL., Zywiak, WH., et al.[2022]

Doxazosin, an α(1)-blocker with a longer half-life than prazosin, has been shown to significantly reduce alcohol intake in preclinical studies without impacting locomotor activity, suggesting its potential as a treatment for alcohol dependence.

This research provides the first preclinical evidence supporting the use of doxazosin for alcohol dependence, indicating a need for further translational studies to explore its clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Commentary: Doxazosin for alcoholism. Leggio, L., Kenna, GA.[2021]

References

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

Receipt of pharmacotherapy for alcohol use disorder by justice-involved women in the Veterans Health Administration. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Reduced alcohol use in patients prescribed pioglitazone. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Extended-release naltrexone for people with alcohol use disorder on therapeutic anticoagulation: A case series. [2022]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Safety and Tolerability of Pharmacological Treatment of Alcohol Dependence: Comprehensive Review of Evidence. [2018]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Novel Agents for the Pharmacological Treatment of Alcohol Use Disorder. [2022]

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

Evaluation of the effect of doxasozin and zonisamide on voluntary ethanol intake in mice that experienced chronic intermittent ethanol exposure and stress. [2023]

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

Safety, efficacy, and lipid profile of doxazosin at a VA medical center. [2013]

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

A Double-Blind Randomized Controlled Trial of Doxazosin for Co-Occurring PTSD and Alcohol Use Disorder in Veterans. [2023]

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

Role of the α1 blocker doxazosin in alcoholism: a proof-of-concept randomized controlled trial. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Commentary: Doxazosin for alcoholism. [2021]