Doxazosin for PTSD and Alcohol Use Disorder

Alcohol Use Disorder Clinical Trial

Official title:

Doxazosin in the Treatment of Co-occuring PTSD and Alcohol Use Disorder

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02492334
• Other study ID #: 3733318
• Status: Completed
• Phase: Phase 2
• Start date: July 2016
• Est. completion date: December 16, 2019

Study information

• Verified date: December 2020
• Source: Medical University of South Carolina
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study will test the efficacy of doxazosin, a long-acting and selective alpha-1 adrenergic antagonist, as compared to placebo in reducing PTSD symptomatology and alcohol use severity.

Description:

As a result of sustained operations in Afghanistan and Iraq, there are an increasing number of U.S. military personnel and Veterans at risk of developing both posttraumatic stress disorder (PTSD) and an alcohol use disorder (AUD). If left untreated, individuals with PTSD/AUD are at risk of developing other mental health problems (e.g., depression, anxiety), suicidal ideation and attempts, physical health problems, reduced resiliency, vocational problems, and family/relationship impairment. While mental health services are in place for U.S. military personnel and Veterans, there are substantial gaps in the evidence base to guide treatment of co-occurring PTSD/AUD. The proposed study directly addresses this gap by testing the efficacy of doxazosin, a long-acting and selective alpha-1 adrenergic antagonist, as compared to placebo in reducing PTSD symptomatology and alcohol use severity among U.S. military personnel (including National Guard and Reservists) who have served in Operation Enduring Freedom, Operation Iraqi Freedom, or Operation New Dawn (OEF/OIF/OND).

The primary objectives of this stage II study are to evaluate the benefits of doxazosin as compared to placebo in reducing (1) PTSD symptomatology, (2) AUD severity, and (3) impairment in associated mental and behavioral health problems (e.g., depression, anxiety, sleep, risky behaviors) among OEF/OIF/OND Veterans (N=126) with co-occurring PTSD and AUD. Secondary objectives are to characterize the underlying pathophysiology of comorbid PTSD/AUD and identify prognostic indicators of treatment outcome using functional magnetic resonance imaging (fMRI). In order to accomplish this the investigators will (1) employ an intent-to-treat, double-blind, placebo-controlled randomized clinical trial that will consist of 12 weeks of treatment with doxazosin or placebo medication; (2) examine standardized, repeated dependent measures of clinical outcomes at 5 time points (baseline, week 4, week 8, week 12, and 1-month follow-up); and (3) employ advanced neuroimaging methodology.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 144
• Est. completion date: December 16, 2019
• Est. primary completion date: November 13, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Male or female; any race or ethnicity; age 21 to 65 years old.

2. U.S. military veteran.

3. Score of > 21 on the Mini Mental Status Exam.

4. Subjects must be able to comprehend English.

5. Meet DSM-5 criteria for current (i.e., last 6 months) alcohol use disorder (AUD).

6. Meet DSM-5 criteria for current (i.e., last 6 months) PTSD.

7. Enrolled in the VAMC Substance Abuse Treatment Clinic (SATC) program.

8. Subjects taking psychotropic medications will be required to be maintained on a stable dose for at least eight weeks before treatment initiation.

9. Must consent to random assignment to doxazosin or placebo.

10. Must consent to complete all treatment and follow-up visits.

11. Must live within 50 miles of the Ralph H. Johnson VAMC in Charleston, SC.

Exclusion Criteria:

1. DSM-5 criteria for a history of or current psychotic or bipolar affective disorders, current eating disorder, as the study protocol may be therapeutically insufficient.

2. DSM-5 criteria for another substance use disorder, except caffeine or nicotine, within the past 12 months.

3. 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.

4. Individuals considered an immediate suicide risk based on the Columbia Suicide Severity rating Scale (C-SSRS) or who are likely to require hospitalization during the course of the study.

5. Previous treatment with doxazosin.

6. 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 will be discontinued from the treatment trial.

7. Women who are pregnant, nursing or not practicing an effective form of birth control.

8. Individuals with a history of or current medical illness including unstable angina, myocardial infarction, congestive heart failure or other cardiac condition, hypotension or hypertension, renal or hepatic disorders, endocrine disorders, prostate or other cancer, pancreatitis, or a seizure disorder.

9. Subjects with abnormal liver function test (LFTs) as evidenced by laboratory findings of SGOT or SGPT greater than two times normal.

10. 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).

11. Individuals currently taking medications to treat hypertension, trazodone, hypnotics/benzodiazepines, mirtazapine, atypical antipsychotics, alpha-2-agonists, prazosin, conivaptan, boceprevir, fusidic acid, idelalisib, PDE-5 inhibitors or alpha-1-antagonists.

12. MRI exclusions: Claustrophobia; tattoos above shoulders; permanent eyeliner or 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; 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.

Related Conditions & MeSH terms

• Alcohol Drinking
• Alcohol Use Disorder
• Alcoholism
• PTSD

Intervention

Drug:
• Doxazosin
Doxazosin is a quinazoline compound that is a selective inhibitor of the alpha-1 subtype of alpha-adrenergic receptors. The chemical name is 1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-(1,4-benzodioxan-2-ylcarbonyl) piperazine methanesulfonate. The molecular formula for doxazosin is C23H25N5O5 • CH4O3S and the molecular weight is 547.6. Doxazosin is used clinically to treat hypertension and improve urination in men with benign prostatic hyperplasia.
• Placebo
Placebo, or inactive pill.

Locations

Country	Name	City	State
United States	Addiction Sciences Division-Medical University of South Carolina	Charleston	South Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Medical University of South Carolina	Ralph H. Johnson VA Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PTSD symptoms	Clinician Administered PTSD Scale	12 weeks
Primary	Alcohol use severity	Time Line Follow Back	12 weeks
Secondary	Characterize the underlying pathophysiology of comorbid PTSD/AUD and prognostic indicators of treatment responses	fMRI	Baseline