Testing Doxazosin to Treat Stress Mechanisms in Alcoholism
Condition: Alcoholism
MeSH terms: Alcoholism
Intervention: Doxazosin; Placebo
Intervention description: Doxazosin; Placebo
Intervention MeSH terms: Doxazosin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 61.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Alcoholism; Stress; Norepinephrine; Doxazosin; Anxiety; Startle Potentiation; Relapse; Adrenergic Antagonists; Surrogate Endpoint

Summary:

      Double-blind, placebo controlled, randomized controlled trial (RCT) for Alcohol Use Disorder
      examining the effects of doxazosin, a norepinephrine alpha1 receptor antagonist, on stress
      reactivity and clinical outcomes.
    

Eligibility criteria:

        INCLUSION CRITERIA:

          -  Diagnostic and Statistical Manual (DSM-5) diagnosis of Alcohol Use Disorder,
             Moderate-Severe

          -  Alcohol abstinent for 1 - 8 weeks

          -  Ages of 18 to 65

        Exclusion criteria are divided into three broad categories of Medical,
        Psychiatric/Behavioral, and Medications/Therapies.

        EXCLUSION CRITERIA: Medical

          -  Blood alcohol concentration above 0.00.

          -  Color blind.

          -  Heart rate >100 beats per minute after five minutes seated.

          -  Heart rate <55 beats per minute after five minutes seated.

          -  Systolic BP <100 after five minutes seated.

          -  Systolic BP drop >20mm Hg or diastolic BP drop >10mm Hg after two minutes standing.

          -  Dizziness, lightheadedness, unsteadiness or other problems (e.g, nausea, blurry
             vision) after two minutes standing.

          -  Uncorrected auditory/vision problems.

          -  Current treatment for chronic pain condition.

          -  Past or current coronary artery disease, cerebrovascular accident, congestive heart
             failure.

          -  Current chronic renal insufficiency, liver insufficiency or moderate hepatic
             impairment, pancreatitis, immunosuppressive therapy, or cancer with systemic effects
             or therapy.

          -  Benign positional vertigo, Meniere's disease, or narcolepsy.

          -  Previous allergic or adverse reaction to doxazosin or other alpha1 noradrenergic
             antagonist.

          -  Scheduled or reported plans for cataract surgery prior to study completion.

          -  Currently symptomatic of alcohol withdrawal [Clinical Institute Withdrawal Assessment
             for Alcohol, revised (CIWA-Ar) Score > 10, or positive for any 'visual, auditory or
             tactile disturbances,' or for 'orientation and clouding of sensorium']

          -  Discharged from inpatient treatment for Alcohol Use Disorder or alcohol detoxification
             within past 7 days.

          -  Currently medically unstable.

          -  Electrocardiogram (ECG) clinical over-read indicates concerns of cardiac function.

          -  Other self-reported acute or unstable illness that, in the opinion of the study team,
             would preclude a safe and reliable study participation

        EXCLUSION CRITERIA: Female Participants Only

          -  Non-negative urine pregnancy test.

          -  Women of childbearing potential (see definition below) must agree to use one of the
             following forms of birth control until after study completion. Acceptable birth
             control is defined as the following methods of contraception: abstinence; hormonal
             contraceptives (e.g. combined oral contraceptives, patch, vaginal ring, injectables,
             and implants); intrauterine device (IUD) or intrauterine system (IUS); vasectomy of
             partner and tubal ligation; "single" barrier methods of contraception (e.g. male
             condom, female condom, cervical cap, diaphragm, contraceptive sponge) with use of
             spermicide; or "double barrier" method of contraception (e.g. male condom with
             diaphragm, male condom with cervical cap).

          -  Breastfeeding.

        NOTE: Women of childbearing potential are females who have experienced menarche and do not
        meet the criteria for women not of childbearing potential. Women not of childbearing
        potential are females who are permanently sterile (e.g., hysterectomy, bilateral
        oophorectomy) or postmenopausal. Postmenopausal is defined as 12 consecutive months with no
        menses without an alternative medical cause.

        EXCLUSION CRITERIA: Psychological/Behavioral

          -  Self-reported lifetime diagnosis of schizophrenia, schizoaffective disorder, psychotic
             disorder not otherwise specified, bipolar disorder (with manic episode), borderline
             personality disorder, or any neurocognitive disorder that may impair a reliable, safe
             participation.

          -  Current suicidal ideation.

          -  Current active substance use disorder other than alcohol or tobacco.

        EXCLUSION CRITERIA: Medications/Therapies

          -  Currently prescribed or used within past week: doxazosin or other alpha1 noradrenergic
             antagonist (e.g., prazosin, terazosin).

          -  Currently prescribed or used within past week: substances with stimulant properties
             (e.g., d-amphetamine, methylphenidate, ephedra, pseudoephedrine).

          -  Currently prescribed or used within past week: Sildenafil (Viagra), tadalafil
             (Cialis), and vardenafil (Levitra).

          -  Currently prescribed or used within past week: beta-blockers (e.g., propanolol),
             alpha2 agonists (e.g., clonidine, guanfacine, dexmedetomidine), and serotonin and
             norepinephrine reuptake inhibitors (SNRI) (e.g., venlafaxine, duloxetine, atomoxetine,
             viloxazine).

          -  Currently used daily or used within past week: alpha1 agonists (e.g., midodrine,
             metaraminol, oxymetazoline, phenylephrine).

          -  Currently used daily or used within past week: Benzodiazepines (e.g., diazepam,
             chlordiazepoxide, lorazepam, clonazepam, alprazolam), zolpidem (Ambien), zaleplon
             (Sonata), zopiclone (Imovane), eszopiclone (Lunesta), doxepin (Silenor).

          -  Currently prescribed and used daily or used within past 2 weeks: Trazodone.

          -  Currently prescribed or used within 2 weeks: Disulfiram (Antabuse).