Doxazosin for Alcohol Use Disorder
(DOXY Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Brown University
Must not be taking: Alpha-blockers, PDE5 inhibitors
Disqualifiers: Pregnancy, Substance disorder, CHF, others
Prior Safety Data
Approved in 5 Jurisdictions
Trial Summary
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.
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?
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.678910
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
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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
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Trial 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 (Alpha-1 Blocker)
- Placebo (Other)
Trial OverviewThe 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
2Treatment groups
Experimental Treatment
Placebo Group
Group I: doxazosinExperimental Treatment1 Intervention
16 mg, or maximum tolerated dose (MTD)
Group II: placeboPlacebo Group1 Intervention
matching placebo
Doxazosin is already approved in European Union, United States, Canada, Japan, Australia 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
🇦🇺 Approved in Australia as Cardura for:
- Benign prostatic hyperplasia
- Hypertension
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Brown UniversityProvidence, RI
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Who Is Running the Clinical Trial?
Brown UniversityLead Sponsor
References
Reduced alcohol use in patients prescribed pioglitazone. [2021]Alcohol use disorder (AUD) is common and causes significant morbidity and mortality. Currently approved medications are moderately effective. Novel medications are needed to address AUD. Preliminary data suggests pioglitazone may reduce alcohol use.
Extended-release naltrexone for people with alcohol use disorder on therapeutic anticoagulation: A case series. [2022]Individuals with medication adherence challenges or a preference for long-acting medications may benefit from extended-release naltrexone (XR-NTX) for treatment of alcohol use disorder (AUD). Individuals on therapeutic anticoagulation were excluded from XR-NTX studies and its safety in this population has not been reported.
Receipt of pharmacotherapy for alcohol use disorder by justice-involved women in the Veterans Health Administration. [2021]Alcohol use disorder (AUD) and unhealthy drinking are prevalent among women involved in the criminal justice system and women military veterans. Pharmacotherapy-including naltrexone, topiramate, acamprosate, and disulfiram-for AUD is one form of effective treatment that is associated with better health and criminal justice outcomes. The current study examined the association of justice involvement with receipt of pharmacotherapy for AUD, as well as other patient factors that may explain variation in receipt of pharmacotherapy for AUD among women veterans who receive care at Veterans Health Administration (VHA) facilities.
Safety and Tolerability of Pharmacological Treatment of Alcohol Dependence: Comprehensive Review of Evidence. [2018]Alcohol use disorders (AUD) cause significant morbidity and mortality worldwide, but pharmacological treatments for them are underused, despite evidence of efficacy. Acamprosate, naltrexone, nalmefene and disulfiram are all approved in one or more region for the treatment of AUD. Baclofen currently has a temporary indication in France. Safety considerations for using psychopharmacological treatments in this patient group include the impact of concurrent alcohol consumption at high levels; multiple physical comorbidities that may interfere with pharmacological effects, distribution and metabolism; and concomitant medication for the treatment of comorbid physical and psychiatric conditions. The five drugs, including an extended-release injectable suspension of naltrexone, have different safety profiles that need to be balanced with the treatment objective (initiation or continuation of abstinence, or reduction of drinking), individual patient preferences and comorbid conditions. Appropriate treatment will be based on the unique risk-benefit profile in each case.
Novel Agents for the Pharmacological Treatment of Alcohol Use Disorder. [2022]Alcohol use disorder (AUD) is a highly prevalent but severely under-treated disorder, with only three widely-approved pharmacotherapies. Given that AUD is a very heterogeneous disorder, it is unlikely that one single medication will be effective for all individuals with an AUD. As such, there is a need to develop new, more effective, and diverse pharmacological treatment options for AUD with the hopes of increasing utilization and improving care. In this qualitative literature review, we discuss the efficacy, mechanism of action, and tolerability of approved, repurposed, and novel pharmacotherapies for the treatment of AUD with a clinical perspective. Pharmacotherapies discussed include: disulfiram, acamprosate, naltrexone, nalmefene, topiramate, gabapentin, varenicline, baclofen, sodium oxybate, aripiprazole, ondansetron, mifepristone, ibudilast, suvorexant, prazosin, doxazosin, N-acetylcysteine, GET73, ASP8062, ABT-436, PF-5190457, and cannabidiol. Overall, many repurposed and novel agents discussed in this review demonstrate clinical effectiveness and promise for the future of AUD treatment. Importantly, these medications also offer potential improvements towards the advancement of precision medicine and personalized treatment for the heterogeneous AUD population. However, there remains a great need to improve access to treatment, increase the menu of approved pharmacological treatments, and de-stigmatize and increase treatment-seeking for AUD.
A Double-Blind Randomized Controlled Trial of Doxazosin for Co-Occurring PTSD and Alcohol Use Disorder in Veterans. [2023]Objective: The aim of this study was to determine the efficacy of doxazosin, an α1-adrenergic antagonist, for the treatment of co-occurring posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD).
Role of the α1 blocker doxazosin in alcoholism: a proof-of-concept randomized controlled trial. [2022]Evidence suggests that the norepinephrine system represents an important treatment target for alcohol dependence (AD) and the α1 -blocker prazosin may reduce alcohol drinking in rodents and alcoholic patients. The α1 -blocker doxazosin demonstrates a more favorable pharmacokinetic profile than prazosin, but has never been studied for AD. A double-blind placebo-controlled randomized clinical trial was conducted in AD individuals seeking outpatient treatment. Doxazosin or matched placebo was titrated to 16 mg/day (or maximum tolerable dose). Drinks per week (DPW) and heavy drinking days (HDD) per week were the primary outcomes. Family history density of alcoholism (FHDA), severity of AD and gender were a priori moderators. Forty-one AD individuals were randomized, 30 (doxazosin = 15) completed the treatment phase and 28 (doxazosin = 14) also completed the follow-up. There were no significant differences between groups on DPW and HDD per week. With FHDA as a moderator, there were significant FHDA × medication interactions for both DPW (pcorrected = 0.001, d = 1.18) and HDD (pcorrected = 0.00009, d = 1.30). Post hoc analyses revealed that doxazosin significantly reduced alcohol drinking in AD patients with high FHDA and by contrast increased drinking in those with low FHDA. Doxazosin may be effective selectively in AD patients with high FHDA. This study provides preliminary evidence for personalized medicine using α1 -blockade to treat AD. However, confirmatory studies are required.
Commentary: Doxazosin for alcoholism. [2021]Recent preclinical and clinical evidence using prazosin indicates that α(1) -blockade may represent a new approach to treat alcohol dependence (AD). While most of the alcohol research on α(1) -blockade has been conducted testing prazosin, O'Neil and colleagues recently performed a set of preclinical experiments testing another α(1) -blocker, doxazosin, which has a longer half-life that may enhance clinical utility. Doxazosin and prazosin share the same chemical structure, in which the central element is a piperazine ring. O'Neil and colleagues' main results are that doxazosin significantly reduced alcohol intake without affecting locomotor activity. As such, O'Neil and colleagues provide the first preclinical evidence of the possible role of doxazosin in AD. Additional translational research is needed to further test this hypothesis.
Evaluation of the effect of doxasozin and zonisamide on voluntary ethanol intake in mice that experienced chronic intermittent ethanol exposure and stress. [2023]The comorbidity between alcohol use disorder and post-traumatic stress disorder represents a serious health care burden with few effective treatment options. The current study was designed to evaluate the effect of an alpha 1 receptor antagonist (doxazosin) and a novel anticonvulsant (zonisamide) in a model of alcohol (ethanol) dependence and stress exposure. The main dependent variable was voluntary ethanol intake in mice that experienced chronic intermittent ethanol (CIE) exposure and forced swim stress (FSS) alone, and in combination. Adult male and female C57BL/6J mice had access to a single bottle of 15% (v/v) ethanol for 1-hr in the home cage, 3-hr into the dark phase of the light/dark cycle. Once stable ethanol intake was established (~4 weeks), mice were separated into four groups (CTL, CIE, FSS, CIE + FSS). Mice in the FSS condition received 10-min FSS exposure 4-hr prior to drinking sessions (remaining mice were not disturbed). During baseline and the first two test cycles, all mice received vehicle (saline) injections (IP) 30-min before ethanol access. As previously observed, FSS increased ethanol drinking in dependent (CIE-exposed) mice but not in nondependent control (CTL) mice. In the following test cycles mice were evaluated for ethanol intake after administration of doxazosin, zonisamide or their combination. Results indicated that the three doses of doxazosin evaluated significantly reduced voluntary ethanol intake in all mice. Zonisamide had a more modest effect and may require a more prolonged treatment regime. The combined administration of both compounds was not more effective than each drug alone. This study suggests that doxazosin is reliable at reducing voluntary ethanol intake in mice independently of their history of ethanol dependence and stress exposure.
Safety, efficacy, and lipid profile of doxazosin at a VA medical center. [2013]The Veterans Administration Lakeside Medical Center (VALMC) is a 500-bed hospital located in downtown Chicago providing a broad scope of inpatient and outpatient medical services for more than 12,000 veterans. The VALMC Pharmacy and Therapeutics Committee requested a study to evaluate doxazosin mesylate (Cardura) to determine if this agent would be an acceptable alternative to other formulary agents. It appears that doxazosin provides several therapeutic advantages, including once-daily dosing, when compared with other more costly antihypertensive agents.