A Randomized Controlled Trial of Doxazosin for Nightmares, Sleep Disturbance, and Non-Nightmare Clinical Symptoms in PTSD

NCT03339258 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: W81XWH-17-1-0234
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized, double-blind, placebo-controlled trial of doxazosin will assess doxazosin's effectiveness for PTSD nightmares, subjective sleep quality, and non-nightmare PTSD symptoms in adult men and women veterans with full and partial-syndromal PTSD.

Conditions

Stress Disorders, Post-Traumatic

Keywords

Posttraumatic Stress Disorder; Post-traumatic Stress Disorder; PTSD; Doxazosin; Nightmares; Sleep Disturbance

Outcome Measures

Primary Outcomes (3)

• Change in Clinician Administered PTSD Scale (CAPS) Distressing Dream Score

  For the assessment of nightmares, the CAPS developed for the DSM-IV will be utilized. The CAPS IV's wide use as an outcome measure in clinical research has provided abundant information about its reliability and responsiveness to change with treatment in general and for nightmares specifically. All existing studies of alpha-blockers for PTS nightmares and non-nightmare symptoms have used the CAPS for DSM-IV, and therefore our results will be more comparable to existing studies. The distressing dreams item from the CAPS for DSM-IV also has strong behavioral anchors, providing detail on both the frequency and intensity of nightmares. A CAPS (DSM-IV) distressing dreams item score of \>=3, as used in prior research on alpha-blockers, will be a requirement for inclusion. Change in CAPS distressing dream score between baseline and end-of-treatment will be the primary measure of the reduction of nightmare frequency/intensity.

  Baseline and Week 9 (end-of-treatment)

• Change in Pittsburgh Sleep Quality Index (PSQI)

  The Pittsburgh Sleep Quality Index (PSQI) is a self-rated questionnaire which assesses sleep quality and disturbances over a 1-month time interval. Nineteen individual items generate seven "component" scores: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. The sum of scores for these seven components yields one global score. Clinical and clinimetric properties of the PSQI were assessed over an 18-month period and acceptable measures of internal homogeneity, consistency (testretest reliability), and validity were obtained. A global PSQI score \> 5 yielded a diagnostic sensitivity of 89.6% and specificity of 86.5% (kappa = 0.75, p 0.001) in distinguishing good and poor sleepers. The clinimetric and clinical properties of the PSQI suggest its utility both in psychiatric clinical practice and research activities.

  Weeks 0, 1, 3, 6, 9 (end-of-treatment)

• Change in CAPS PTS Symptom Score

  Change in total CAPS score, minus the distressing dreams item score

  Baseline and Week 9 (end-of-treatment)

Secondary Outcomes (8)

• Change in minutes of wake after sleep onset (WASO)

  Daily, weeks 0-8

• Change in total sleep time (TST)

  Daily, weeks 0-8

• Change in sleep maintenance (SM)

  Daily, weeks 0-8

• Nightmare Distress Questionnaire (NDQ)

  Weeks 0, 1, 3, 6, 9 (end-of-treatment)

• PTSD Checklist for DSM- 5 (PCL-5)

  Weeks 0, 1, 3, 6, 9 (end-of-treatment)

Other Outcomes (5)

• Beck Depression Inventory (BDI)

  Weeks 0, 1, 3, 6, and 9 (end-of-treatment)

• Sexual Health Inventory for Men (SHIM)

  Weeks 0, 1, 3, 6, and 9 (end-of-treatment)

• Male Sexual Health Questionnaire (MSHQ)

  Weeks 0, 1, 3, 6, and 9 (end-of-treatment)

Study Arms (2)

Doxazosin Mesylate, Extended Release

EXPERIMENTAL

Subjects will undergo a 4-week titration phase during which doxazosin may be increased to a maximum dose of 10mg at bedtime based on symptoms and tolerability. After the 4-week titration phase, subjects will continue at stable dose of study medication for a 4-week stable dose phase.

Drug: Doxazosin Mesylate, Extended Release

Placebo

PLACEBO COMPARATOR

Subjects will undergo a 4-week titration phase during which the placebo may be increased to a maximum dose of 10mg at bedtime based on symptoms and tolerability. After the 4-week titration phase, subjects will continue at stable dose of study placebo for a 4-week stable dose phase.

Drug: Placebo

Interventions

Doxazosin Mesylate, Extended Release DRUG

Doxazosin is FDA-approved for the treatment of hypertension and urinary outflow problems associated with benign prostatic hyperplasia. The immediate-release formulation is approved for use from 1mg up to 16mg. Based on drug company information and Micromedex, the SFVA pharmacy on-line reference resource for drug information, the only contraindication to use of doxazosin is hypersensitivity to doxazosin, its contents, or other quinazolines (e.g. prazosin, terazosin).

Also known as: Cardura XL

Doxazosin Mesylate, Extended Release

Placebo DRUG

Placebo, or inactive pill.

Also known as: Sugar pill

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• U.S. military veteran or civilian;
• age 18-75 and
• current full syndromal PTS as indexed by the CAPS-5 (Clinician-administered PTSD scale) or have a current CAPS-5 score ≥ 20, and CAPS-IV recurrent distressing dreams item of ≥ 3; or a CAPS-5 score ≥ 12, and CAPS-IV recurrent distressing dream item of ≥ 4.

You may not qualify if:

• DSM-5 current moderate to severe alcohol or drug use disorder in the last 3 months; moderate alcohol or drug use disorder in the last 3 months will be reviewed on a case-by-case basis;
• history of any psychiatric disorder with active psychosis or mania in the past 5 years;
• exposure to trauma within the last 3 months;
• prominent suicidal or homicidal ideation;
• score of 16 or greater AHI based on ApneaLink data analysis in the absence of effective sleep treatment (such as CPAP or oral device)
• neurologic disorder or systemic illness affecting central nervous system function;
• chronic or unstable medical illness including unstable angina, myocardial infarction within the past 6 months, congestive heart failure, preexisting hypotension or standing systolic blood pressure \< 100 mmHg at eligibility (V0); orthostatic hypotension defined as orthostatic systolic decrease after 3 minutes standing \>20 mmHg or any BP decrease accompanied by lightheadedness; complete heart block or arrhythmia on ECG; chronic renal or hepatic failure, and pancreatitis;
• history of priapism or refusal to hold off on as needed phosphodiesterase inhibitors;
• pregnancy, breastfeeding and/or refusal to use effective birth control (female participants);
• previous adverse reaction to an alpha-1-antagonist;
• current use of a medication with alpha-1 blocking properties for insomnia, alpha-1 antagonists, alpha-2 agonists, boceprevir; midodrine; and
• use of yohimbine, Ma huang or other non-FDA approved substances or herbal remedies that the investigators consider pose a risk to participation
• homelessness (includes living in a temporary shelter);
• subjects who, in the opinion of the investigator, are otherwise unsuitable for a study of this type.
• Participants taking SSRIs, duloxetine, bupropion, mirtazapine, and venlafaxine may be included if they have been on a stable dose for 4 weeks. Participants may be included if they are in psychotherapy treatment as long as they do not participate in evidence-based trauma-focused or nightmare-focused psychotherapy (such as cognitive processing therapy, prolonged exposure therapy, or imagery rehearsal therapy) while in the trial. Participants who are normotensive and do not have orthostatic hypotension while on stable-dose beta-blocker may be included in the study.

Sponsors & Collaborators

• San Francisco Veterans Affairs Medical Center: lead
• United States Department of Defense: collaborator
• Northern California Institute of Research and Education: collaborator

Study Sites (1)

San Francisco VA Medical Center

San Francisco, California, 94121, United States

Location

Related Publications (2)

• De Jong J, Wauben P, Huijbrechts I, Oolders H, Haffmans J. Doxazosin treatment for posttraumatic stress disorder. J Clin Psychopharmacol. 2010 Feb;30(1):84-5. doi: 10.1097/JCP.0b013e3181c827ae. No abstract available.

  PMID: 20075659 BACKGROUND

• Richards A, Santistevan AC, Yack LM, West AC, Berg E, Pracar S, Batki SL, Seal KH, Neylan TC. A double-blind, randomized, placebo-controlled trial of doxazosin for posttraumatic distressing dreams and sleep disturbance in men and women with posttraumatic stress. J Clin Sleep Med. 2025 Dec 1;21(12):2165-2179. doi: 10.5664/jcsm.11908.

  PMID: 41042258 DERIVED

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic; Parasomnias

Interventions

Doxazosin; Sugars

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders; Sleep Wake Disorders; Nervous System Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Anne Richards, MD, MPH

  San Francisco Veterans Affairs Medical Center

  PRINCIPAL INVESTIGATOR

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: PRINCIPAL INVESTIGATOR
• PI Title: Staff Psychiatrist

Study Record Dates

• First Submitted: November 6, 2017
• First Posted: November 13, 2017
• Study Start: April 15, 2018
• Primary Completion: June 1, 2024
• Study Completion: June 1, 2024
• Last Updated: May 1, 2024

Record last verified: 2024-04

Locations

US (1)