CAP: Doxazosin in the Treatment of Co-Occurring PTSD and Alcohol Use Disorders

NCT02500602 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: SPLE-001-14FCX001288
• Study Type: interventional
• Target: 144
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Posttraumatic Stress Disorder; Alcohol Use Disorders

Keywords

PTSD; alcohol use disorders; posttraumatic stress disorder; AUD; Veteran; substance use disorders; SUD

Outcome Measures

Primary Outcomes (3)

• Clinician Administered PTSD Scale

  The primary PTSD outcome measure was the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5; Weathers et al., 2013). The CAPS-5 is a semi-structured interview that measures the DSM-5 symptoms of PTSD and requires the presence of at least one intrusion symptom, one avoidance symptom, two cognition and mood symptoms, and two arousal symptoms for a period of 1 month or more to reach diagnostic threshold. There are 20 symptom items and responses that are rated on a 5-point scale ranging from 0 (absent) to 4 (extreme/incapacitating), with a total PTSD symptom severity score of the sum of the 20 symptom items ranging from 0-80, and lower scores indicating better outcomes (or less severe PTSD symptomology). The CAPS-5 was assessed at end of treatment (week 12).

  12 Weeks

• PTSD Checklist (PCL-5)

  The secondary PTSD outcome measure was the PTSD Checklist-5 (PCL-5; Weathers et al., 2013b). The PCL-5 is 20-item self-report measure that assesses the DSM-5 symptoms of PTSD using a severity rating Likert scale ranging from 0 to 4 that indicates the degree of distress across symptoms (0 = not at all to 4 = extremely). The overall score range is 0-80 (and combines the score for all 20 symptoms), with lower scores representing better outcomes (less severe PTSD symptomology). The PCL-5 was assessed at end of treatment (week 12).

  12 Weeks

• Time Line Follow Back (TLFB)

  The TLFB obtains retrospective self-report of substance use by using a calendar and memory prompts to stimulate recall (Sobell \& Sobell, 1992). Quantity and frequency assessments are made using this instrument (e.g., total number of standard drink units, percent of days using) as well as abstinence (yes/no). TLFB yields consistently high test-retest correlations and correlates well with other self-reports and collateral reports (Sobell et al., 2003). The TLFB assesses frequency and amount of substance use over a pre-determined timeframe. TLFB data were collected throughout the trial, and the values reported here represent the TLFB data at end of treatment (week 12).

  12 Weeks

Study Arms (2)

Doxazosin

EXPERIMENTAL

Participants randomly assigned to receive doxazosin (target dose of 16 mg/day). Doxazosin will be initiated at 1 mg/day for the first week, 2mg/day for the second week, 4mg/day for the third week, 8mg/day for the fourth week, and then increase to 16 mg/day for the remaining eight weeks (as tolerated). Research staff administered the study medication at the weekly visits, and participants were given take-home doses of the medication to self-administer on the days in between study visits.

Drug: doxazosin

Placebo

PLACEBO COMPARATOR

Participants randomly assigned to placebo. Research staff administered the study medication at the weekly visits, and participants were given take-home doses of the medication to self-administer on the days in between study visits.

Drug: placebo

Interventions

doxazosin DRUG

active medication

Doxazosin

placebo DRUG

placebo pill

Placebo

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female; any race or ethnicity.
• Served in U.S. Military - any branch or operation.
• Subjects must be able to comprehend English.
• 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).
• Meet DSM-5 criteria for current (i.e., last month) PTSD.
• 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.
• Must consent to random assignment to doxazosin or placebo.
• Must consent to complete all treatment and follow-up visits.

You may not qualify if:

• Subjects meeting DSM-5 criteria for current bipolar affective disorders, as the study protocol may be therapeutically insufficient.
• 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.
• Individuals considered an immediate suicide risk or who are likely to require hospitalization during the course of the study.
• Previous treatment with doxazosin.
• 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.
• Women who are pregnant, nursing or not practicing an effective form of birth control.
• 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.
• Subjects with abnormal liver function test (LFTs) as evidenced by laboratory findings of SGOT or SGPT greater than two times normal.
• 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).
• 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.

Sponsors & Collaborators

• VA Office of Research and Development: lead
• Medical University of South Carolina: collaborator

Study Sites (1)

Ralph H. Johnson VA Medical Center, Charleston, SC

Charleston, South Carolina, 29401-5799, United States

Location

Related Publications (1)

• Back SE, Flanagan JC, Mintz J, Brady KT, Jones J, Jarnecke AM, Joseph JE, Shirley DW, Malcolm RJ, Hamner M, Litz BT, Niles BL, Young-McCaughan S, Keane TM, Peterson AL. A Double-Blind Randomized Controlled Trial of Doxazosin for Co-Occurring PTSD and Alcohol Use Disorder in Veterans. J Clin Psychiatry. 2023 Mar 8;84(2):21m14367. doi: 10.4088/JCP.21m14367.

  PMID: 36883885 DERIVED

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic; Alcoholism; Substance-Related Disorders

Interventions

Doxazosin

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders; Alcohol-Related Disorders; Chemically-Induced Disorders

Intervention Hierarchy (Ancestors)

Prazosin; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Sudie Back
• Organization: Medical University of South Carolina

backs@musc.edu

843-792-9383

Study Officials

• Sudie E. Back, PhD

  Ralph H. Johnson VA Medical Center, Charleston, SC

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2015
• First Posted: July 16, 2015
• Study Start: June 1, 2016
• Primary Completion: December 16, 2019
• Study Completion: December 16, 2019
• Last Updated: May 13, 2021
• Results First Posted: April 14, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: ICF

Locations

US (1)