CAP: Doxazosin in the Treatment of Co-Occurring PTSD and Alcohol Use Disorders
Condition: Posttraumatic Stress Disorder; Alcohol Use Disorders
MeSH terms: Alcoholism; Stress Disorders, Traumatic; Alcohol Drinking; Stress Disorders, Post-Traumatic
Intervention: doxazosin; placebo
Intervention description: active medication; placebo pill
Intervention MeSH terms: Doxazosin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 144.0
Sex: All
Healthy volunteers: No
Keywords: PTSD; alcohol use disorders; posttraumatic stress disorder; AUD; Veteran; substance use disorders; SUD

Summary:

      The proposed study will examine the efficacy of doxazosin in the treatment of PTSD and
      alcohol use disorder or substance use disorders.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female; any race or ethnicity.

          2. Served in U.S. Military - any branch or operation.

          3. Subjects must be able to comprehend English.

          4. Meet criteria for current (i.e., last 6 months) Substance Use Disorder (SUD) using a
             modified version of the MINI 7.0 (i.e., must meet DSM-5 criteria for SUD in the past 6
             months instead of 12 months).

          5. Meet DSM-5 criteria for current (i.e., last month) PTSD.

          6. Subjects taking psychotropic medications will be required to be maintained on a stable
             dose for at least four weeks before treatment initiation. This is because initiation
             or change of medications during the course of the trial may interfere with
             interpretation of results.

          7. Must consent to random assignment to doxazosin or placebo.

          8. Must consent to complete all treatment and follow-up visits.

        Exclusion Criteria:

          1. Subjects meeting DSM-5 criteria for current bipolar affective disorders, as the study
             protocol may be therapeutically insufficient.

          2. Subjects experiencing significant withdrawal symptoms, as evidence by a score of 10 or
             above on the Clinical Institute Withdrawal Assessment of Alcohol (CIWA). These subject
             will be referred for clinical detoxification and may be re-assessed for study
             eligibility after medically supervised detoxification has been completed.

          3. Individuals considered an immediate suicide risk or who are likely to require
             hospitalization during the course of the study.

          4. Previous treatment with doxazosin.

          5. Subjects on maintenance anxiolytic, antidepressant, or mood stabilizing medications
             which have been initiated during the past four weeks. If it is determined, based on
             clinical criteria, that a subject needs to be started on maintenance medications for
             anxiety, mood or psychotic symptoms during the course of the study, they may be
             discontinued from the treatment trial.

          6. Women who are pregnant, nursing or not practicing an effective form of birth control.

          7. Individuals with a history of or current medical illness including unstable angina,
             myocardial infarction, congestive heart failure or other cardiac condition,
             hypotension, renal or hepatic disorders, endocrine disorders, prostate or other
             cancer, pancreatitis, or a seizure disorder.

          8. Subjects with abnormal liver function test (LFTs) as evidenced by laboratory findings
             of SGOT or SGPT greater than two times normal.

          9. Subjects with a history of adverse reactions to quinazolines or other
             alpha-1-antagonists (such as allergic reactions, priapism, hepatitis, angioedema, or
             intraoperative floppy iris syndrome).

         10. Individuals currently taking alpha blockers (terazosin, prazosin),
             hypnotics/benzodiazepines, atypical antipsychotics (olanzapine, quetiapine,
             risperidone, clozapine), alpha-2-agonists (Clonidine, methyldopa, tizanidine,
             guanfacine), conivaptan, boceprevir, idelalisib, PDE-5 inhibitors or
             alpha-1-antagonists, protease inhibitors (treatment of HIV), oral antifungals,
             alfuzosin, pazopanib, silodosin, tadalafil, or tamulosin.

         11. MRI exclusions: Claustrophobia; tattoos above the shoulders after evaluation by MRI
             technician; permanent eyeliner or permanent artificial eyebrows; cardiac pacemaker;
             metal fragments in eye, skin, or body, including shrapnel; heart valve replacement;
             brain clips; venous umbrella; being a sheet-metal worker or welder; lifetime history
             of aneurysm surgery; intracranial bypass, renal, or aortic clips; prosthetic devices
             such as middle ear, eye, joint, or penile implants; joint replacements; non-removable
             hearing aid, neurostimulator, or insulin pump; shunts/stents; metal mesh/coil
             implants; metal plate/pin/screws/wires; or any other metal implants.