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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a medication called doxazosin to determine if it can help people with Alcohol Use Disorder (AUD) who want to reduce or quit drinking. Researchers aim to understand how stress affects AUD and how doxazosin, which blocks certain stress-related signals in the brain, might assist. Participants will receive either doxazosin or a placebo (a pill with no active medicine) to compare results. This trial suits individuals who meet the criteria for AUD, are in good health, and do not currently use certain medications that might interfere with the study. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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 there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that doxazosin has been safely used since its approval in 1990. Studies have found that most people tolerate this medication well, though some might experience side effects like fatigue, dizziness, or low blood pressure.

In past research, doxazosin was tested on individuals with PTSD and alcohol use disorder. The results indicated that doxazosin was safe for these patients, even though it did not outperform a placebo in reducing symptoms. The safety profile remained positive.

Since this trial is in Phase 2, doxazosin has already undergone initial safety testing in earlier trials. This provides some evidence suggesting its safety for people. Always consult a healthcare provider about any concerns before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for alcohol use disorder?

Most treatments for Alcohol Use Disorder, like naltrexone and acamprosate, work by modifying brain chemistry to reduce cravings or withdrawal symptoms. But doxazosin offers a unique approach by targeting the body's noradrenergic system, which is involved in stress response and impulse control. Researchers are excited about doxazosin because it has the potential to reduce alcohol consumption by calming the stress pathways that often drive excessive drinking, offering a fresh angle compared to standard therapies.

What evidence suggests that Doxazosin might be an effective treatment for Alcohol Use Disorder?

In this trial, participants will receive either 16 mg of doxazosin or a placebo. Research has shown that taking 16 mg of doxazosin daily may help reduce alcohol consumption. One study found that people taking doxazosin drank less each week, had fewer days of heavy drinking, and experienced fewer cravings. It appears to work better for some individuals, particularly those with a family history of alcohol problems. However, another study found that doxazosin was no more effective than a placebo for people with both PTSD and alcohol use disorder. These mixed results suggest that doxazosin might help some individuals, but not everyone. ^{1 3 4 6 7}

Who Is on the Research Team?

Carolina L Haass-Koffler, PHARMD, PHD

Principal Investigator

Brown University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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, 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]

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 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]

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]

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 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6291829/

Doxazosin for the treatment of co-occurring PTSD and alcohol ... [28] found that doxazosin (16 mg/day) was associated with significantly lower reductions in drinks per week, heavy drinking days, and craving among individuals ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4668239/

Role of the α1 Blocker Doxazosin in Alcoholism Post-hoc analyses revealed that doxazosin significantly reduced alcohol drinking in AD patients with high FHDA and by contrast increased drinking in those with ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03398252?term=AREA%5BBasicSearch%5D(Doxazosin)&rank=10

Targeting Stress-Induced Alcohol Relapse Risk With ... Participants will be randomized to receive either increasing doses of doxazosin XL (0, 4, and 8 mg) or placebo in a double-blind manner. Official Title.

4. psychiatrist.com psychiatrist.com/jcp/double-blind-randomized-controlled-trial-doxazosin-co-occurring-ptsd-alcohol-use-disorder-veterans/

A Double-Blind Randomized Controlled Trial of Doxazosin ... Doxazosin was safe and tolerable but was not more effective than placebo in reducing PTSD or AUD severity in this dually diagnosed sample.

5. clinicaltrials.eu clinicaltrials.eu/inn/doxazosin/

Doxazosin: A Comprehensive Guide for Patients Alcohol Dependence: Preliminary studies are investigating if doxazosin can help reduce alcohol consumption in people with alcohol use disorder. How ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2021/019668Orig1s032lbl.pdf

CARDURA (doxazosin) Label - accessdata.fda.gov Initial U.S. Approval: 1990. The most commonly reported adverse reactions from clinical trials are. Fatigue, malaise, hypotension, and dizziness. (6.1).

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6561397/

Pharmacotherapy for Co-Occurring Alcohol Use Disorder ... Doxazosin XL reduces symptoms of posttraumatic stress disorder in veterans with PTSD: A pilot clinical trial. J Clin Psychiatry. 2016;77(5):e561–e565. doi ...