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Trial record 3 of 2153 for:    Symptoms | Parasomnias

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

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ClinicalTrials.gov Identifier: NCT03339258
Recruitment Status : Recruiting
First Posted : November 13, 2017
Last Update Posted : April 19, 2018
Sponsor:
Collaborators:
United States Department of Defense
Northern California Institute of Research and Education
Information provided by (Responsible Party):
Anne Richards, San Francisco Veterans Affairs Medical Center

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.

Condition or disease Intervention/treatment Phase
Stress Disorders, Post-Traumatic Drug: Doxazosin Mesylate, Extended Release Drug: Placebo Phase 2

Detailed Description:
This study will involve a randomized, double-blind, placebo-controlled, flexible dose trial of doxazosin (1-16mg) for PTSD nightmares, sleep disturbance and overall PTSD symptoms. The target sample will consist of 60 male and female subjects with chronic PTSD symptoms and prominent nightmares randomly assigned to receive doxazosin (n=30) or placebo (n=30). Participants will be enrolled at the San Francisco VA Medical Center. Following baseline consent procedures, eligibility assessments, and 1-week of baseline assessments including self-report surveys and actigraphy, all subjects will initiate doxazosin or equivalently marked placebo at 1mg at bedtime. Subjects will undergo a 4-week titration phase during which doxazosin or placebo may be increased to a maximum dose of 16mg (or equivalently marked placebo) 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. Subjects will be asked to complete sleep diaries daily during their participation in the study. In the last week of the stable dose phase, participants will undergo an additional week of at-home sleep monitoring using actigraphy, complete end of treatment surveys, and undergo end-of-treatment clinical assessments and discontinuation of study medication.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled Trial of Doxazosin for Nightmares, Sleep Disturbance, and Non-Nightmare Clinical Symptoms in Post-Traumatic Stress
Actual Study Start Date : April 15, 2018
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : June 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Sleep Disorders

Arm Intervention/treatment
Experimental: Doxazosin Mesylate, Extended Release
Subjects will undergo a 4-week titration phase during which doxazosin may be increased to a maximum dose of 16mg 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
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).
Other Name: Cardura XL

Placebo Comparator: Placebo
Subjects will undergo a 4-week titration phase during which the placebo may be increased to a maximum dose of 16mg 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
Placebo, or inactive pill.
Other Name: Sugar pill




Primary Outcome Measures :
  1. Change in Clinician Administered PTSD Scale (CAPS) Distressing Dream Score [ Time Frame: Baseline and Week 9 (end-of-treatment) ]
    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 >=5, 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.

  2. Change in Pittsburgh Sleep Quality Index (PSQI) [ Time Frame: Weeks 0, 1, 3, 6, 9 (end-of-treatment) ]
    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.

  3. Change in CAPS PTS Symptom Score [ Time Frame: Baseline and Week 9 (end-of-treatment) ]
    Change in total CAPS score, minus the distressing dreams item score


Secondary Outcome Measures :
  1. Change in minutes of wake after sleep onset (WASO) [ Time Frame: Daily, weeks 0-8 ]
    Each morning the subject will record the clock times of their sleep onset and offset, number of nighttime awakenings, wake time in minutes after sleep onset (WASO), number of nightmares and intensity of the worst nightmare on a 10-point scale. They will also rate their sleep quality on a scale from 1-100. From this data, measures of TST, WASO, and SM can be calculated.

  2. Change in total sleep time (TST) [ Time Frame: Daily, weeks 0-8 ]
    Each morning the subject will record the clock times of their sleep onset and offset, number of nighttime awakenings, wake time in minutes after sleep onset (WASO), number of nightmares and intensity of the worst nightmare on a 10-point scale. They will also rate their sleep quality on a scale from 1-100. From this data, measures of TST, WASO, and SM can be calculated.

  3. Change in sleep maintenance (SM) [ Time Frame: Daily, weeks 0-8 ]
    Each morning the subject will record the clock times of their sleep onset and offset, number of nighttime awakenings, wake time in minutes after sleep onset (WASO), number of nightmares and intensity of the worst nightmare on a 10-point scale. They will also rate their sleep quality on a scale from 1-100. From this data, measures of TST, WASO, and SM can be calculated.

  4. Nightmare Distress Questionnaire (NDQ) [ Time Frame: Weeks 0, 1, 3, 6, 9 (end-of-treatment) ]
    The NDQ is a self-report assessment of the degree of distress that nightmares cause, and is shown to be a valid, reliable measure of the effects of nightmares.

  5. PTSD Checklist for DSM- 5 (PCL-5) [ Time Frame: Weeks 0, 1, 3, 6, 9 (end-of-treatment) ]
    The PCL-5 will be used as a secondary measure and to assess the internal consistency of the CAPS PTSD symptom score. The PCL-5 is a validated self-report rating scale for assessing PTSD symptoms. It consists of 20 items that correspond to the DSM-5 symptoms of PTSD.

  6. Objective measure of change in TST [ Time Frame: All subjects will wear the actigraph daily for 7 days at pre-treatment baseline (week 0), 7 days in week 5 of study drug treatment, and at end-of-treatment week 8 prior to drug discontinuation. ]
    The AMI Octagonal Basic Motionlogger (www.ambulatorymonitoring.com), which is worn on the wrist like a watch, is an advanced actigraph which has sufficient memory to record movements for up to 28 days. As indicated by the American Academy of Sleep Medicine Standards of Practice Committee, actigraphy can improve the reliability of self-report estimates of sleep wake timing and may play an important 15 role in the diagnosis and treatment of insomnia. It is also appropriate for the assessment of stability of treatment effects, including the assessment of changes in night-to-night variability in various sleep measures. Our lab has used this actigraph extensively, providing support for its usability in research subjects. High resolution data can be down-sampled for actigraphic sleep-wake estimation.

  7. Objective measure of change in WASO [ Time Frame: All subjects will wear the actigraph daily for 7 days at pre-treatment baseline (week 0), 7 days in week 5 of study drug treatment, and at end-of-treatment week 8 prior to drug discontinuation. ]
    The AMI Octagonal Basic Motionlogger (www.ambulatorymonitoring.com), which is worn on the wrist like a watch, is an advanced actigraph which has sufficient memory to record movements for up to 28 days. As indicated by the American Academy of Sleep Medicine Standards of Practice Committee, actigraphy can improve the reliability of self-report estimates of sleep wake timing and may play an important 15 role in the diagnosis and treatment of insomnia. It is also appropriate for the assessment of stability of treatment effects, including the assessment of changes in night-to-night variability in various sleep measures. Our lab has used this actigraph extensively, providing support for its usability in research subjects. High resolution data can be down-sampled for actigraphic sleep-wake estimation.

  8. Objective measures of change in SM [ Time Frame: All subjects will wear the actigraph daily for 7 days at pre-treatment baseline (week 0), 7 days in week 5 of study drug treatment, and at end-of-treatment week 8 prior to drug discontinuation. ]
    The AMI Octagonal Basic Motionlogger (www.ambulatorymonitoring.com), which is worn on the wrist like a watch, is an advanced actigraph which has sufficient memory to record movements for up to 28 days. As indicated by the American Academy of Sleep Medicine Standards of Practice Committee, actigraphy can improve the reliability of self-report estimates of sleep wake timing and may play an important 15 role in the diagnosis and treatment of insomnia. It is also appropriate for the assessment of stability of treatment effects, including the assessment of changes in night-to-night variability in various sleep measures. Our lab has used this actigraph extensively, providing support for its usability in research subjects. High resolution data can be down-sampled for actigraphic sleep-wake estimation.


Other Outcome Measures:
  1. Beck Depression Inventory (BDI) [ Time Frame: Weeks 0, 1, 3, 6, and 9 (end-of-treatment) ]
    The BDI is a widely used self-report measure which includes subjective ratings of 21 depressive symptoms.

  2. Sexual Health Inventory for Men (SHIM) [ Time Frame: Weeks 0, 1, 3, 6, and 9 (end-of-treatment) ]
    The SHIM is a well-validated measure used in urology research, will be utilized to assess the effects of doxazosin on erectile function in men, the aspect of sexual functioning that may be most affected by doxazosin.

  3. Male Sexual Health Questionnaire (MSHQ) [ Time Frame: Weeks 0, 1, 3, 6, and 9 (end-of-treatment) ]
    The MSHQ will be utilized as a more global measure of sexual health, encompassing erectile function, ejaculatory function, and satisfaction in men.

  4. Female Sexual Functioning Index (FSFI) [ Time Frame: Weeks 0, 1, 3, 6, and 9 (end-of-treatment) ]
    The FSFI will be used to assess for various elements of sexual functioning in women, including arousal and satisfaction.

  5. World Health Organization Quality of Life inventory (WHOQOL-BREF) [ Time Frame: Weeks 0, 1, 3, 6, and 9 (end-of-treatment) ]
    The WHOQOL-BREF instrument comprises 26 items, which measure the following broad domains: physical health, psychological health, social relationships, and environment. The WHOQOL-BREF is a shorter version of the original instrument and more convenient for use in clinical trials.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 69 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • U.S. military veteran;
  • age 18-69 and
  • current full syndromal PTS as indexed by the CAPS-5 (Clinician-administered PTSD scale) or partial syndromal PTS of at least 3 months duration with a CAPS-5 score >25, and CAPS-IV recurrent distressing dreams item of >/= 5.

Exclusion Criteria:

  • DSM-5 current moderate to severe alcohol or drug use disorder;
  • lifetime history of any psychiatric disorder with psychotic features, bipolar disorder, obsessive-compulsive disorder;
  • exposure to trauma within the last 3 months;
  • prominent suicidal or homicidal ideation;
  • pre-existing sleep apnea diagnosis in the absence of adherence to effective treatment (such as Continuous Positive Airway Pressure (CPAP) or oral device) or positive screen for sleep apnea by type III 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 baseline standing systolic blood pressure < 110 mmHg; orthostatic hypotension defined as orthostatic systolic decrease after 3 minutes standing >20 mmHg or any BP decrease accompanied by lightheadedness; heart block or arrhythmia on ECG; chronic renal or hepatic failure, and pancreatitis;
  • history of priapism;
  • pregnancy, breastfeeding and/or refusal to use effective birth control (female participants);
  • previous adverse reaction to an alpha-1-antagonist;
  • current use of trazodone, sedative-hypnotics or benzodiazepines, atypical antipsychotics, 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03339258


Contacts
Contact: Andrew Levihn-Coon, B.A. 415-221-4810 ext 23809 andrew.levihn-coon@va.gov

Locations
United States, California
San Francisco VA Medical Center Recruiting
San Francisco, California, United States, 94121
Contact: Andrew Levihn-Coon, B.A.    415-221-4810 ext 23809    andrew.levihn-coon@va.gov   
Sponsors and Collaborators
San Francisco Veterans Affairs Medical Center
United States Department of Defense
Northern California Institute of Research and Education
Investigators
Principal Investigator: Anne Richards, MD, MPH San Francisco Veterans Affairs Medical Center

Additional Information:
Publications:
Responsible Party: Anne Richards, Staff Psychiatrist, San Francisco Veterans Affairs Medical Center
ClinicalTrials.gov Identifier: NCT03339258     History of Changes
Other Study ID Numbers: W81XWH-17-1-0234
First Posted: November 13, 2017    Key Record Dates
Last Update Posted: April 19, 2018
Last Verified: April 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Anne Richards, San Francisco Veterans Affairs Medical Center:
Posttraumatic Stress Disorder
Post-traumatic Stress Disorder
PTSD
Doxazosin
Nightmares
Sleep Disturbance

Additional relevant MeSH terms:
Sleep Wake Disorders
Parasomnias
Signs and Symptoms
Stress Disorders, Traumatic
Dyssomnias
Stress Disorders, Post-Traumatic
Trauma and Stressor Related Disorders
Mental Disorders
Nervous System Diseases
Neurologic Manifestations
Doxazosin
Antihypertensive Agents
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs