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PTSDPhase 3PACTNCT00532493

Cooperative Studies Program #563 - Prazosin and Combat Trauma PTSD

A Phase 3 study testing prazosin in people with PTSD and Sleep Disorders, run by VA Office of Research and Development at 15 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Background: Posttraumatic stress disorder (PTSD) is a debilitating and disabling mental disorder that afflicts at least 25% of Veterans who have suffered life-threatening war zone trauma. Trauma-related nightmares and sleep disturbance are among the most treatment-resistant PTSD symptoms in Veterans. Read more about this study

Who is it for?
Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for
PTSD, Sleep Disorders
What is being tested?
prazosin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
304 participants
Where
15 sitesUnited States
Study dates
6 Jan 2010to 31 May 2013
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Age >18 years.
  • Exposure to one or more life-threatening war zone trauma events per the Combat
  • Exposure Scale [78] and documented by Department of Defense (DD) Form 214, Combat Action Ribbon (Marines), Combat Infantry Badge (Army), or other clear evidence of war zone trauma exposure.
  • Eligible for VA health care.
  • Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV diagnosis of PTSD derived from the CAPS.
  • CAPS total score >50.
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  • CAPS Recurrent Distressing Dreams item score >5 (of maximum score of 8).
  • Capable of giving informed consent.
  • Stable dose of non-exclusionary (see below) medications for at least 4 weeks prior to randomization.
  • Psychotherapeutic treatment stable for at least 4 weeks prior to randomization.
  • Good general medical health (see Medical Exclusion Criteria below).
  • Female participants must agree to use a reliable form of birth control during the study.

Who cannot join

  • Medical:
  • Acute or unstable chronic medical illness, including unstable angina, recent myocardial infarction (within 6 months), congestive heart failure, preexisting hypotension (systolic <110) or orthostatic hypotension (systolic drop > 20 millimeters of mercury after two minutes standing or any drop accompanied by dizziness); chronic renal or hepatic failure, pancreatitis, Meniere's disease, benign positional vertigo; narcolepsy.
  • Untreated sleep apnea, diagnosed by a sleep study, is exclusionary. Treated sleep apnea (e.g., Continuous Positive Airway Pressure, surgery) will not be exclusionary.
  • Allergy or previous adverse reaction to prazosin or other alpha-1 antagonist.
  • Wounds requiring surgery, embedded shrapnel, and recent surgical amputation do not comprise an exclusion if the individual is otherwise medically eligible.
  • Women of childbearing potential with positive pregnancy test or refusal to use effective birth control method, or who are breastfeeding will be excluded.
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  • Psychiatric/Behavioral:
  • Meets DSM-IV criteria for current schizophrenia, schizoaffective disorder, psychotic disorder not otherwise specified (NOS), delirium, or any DSM-IV cognitive disorder.
  • Exclusion for psychotic disorder is not to be confused with combat trauma-induced reexperiencing symptoms (transient dissociative states or flashbacks), which will not be exclusionary.
  • Substance dependence disorder within 3 months or any current substance dependence (stable methadone maintenance will not be exclusionary).
  • Current cocaine or stimulant abuse.
  • Severe psychiatric instability or severe situational life crises, including evidence of being actively suicidal or homicidal, or any behavior which poses an immediate danger to patient or others.
  • Nonsuicidal depression comorbid with PTSD will not be exclusionary (see below).
  • Medications/Therapies:
  • Current use of prazosin or other alpha-1 antagonist.
  • Previous adequate trial of prazosin for PTSD.
  • Subjects on trazodone will undergo a 2-week washout period before baseline assessment. (Combining prazosin and trazodone may increase risk of priapism).
  • Sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra) will be not be permitted during the study dose titration period because of increased risk of hypotension in combination with alpha-1 blockers. Following achieving stable dose of study drug, sildenafil, tadalafil, and vardenafil will be permitted at 1/2 the usual starting dose.
  • Stimulants or alternative medications with stimulant properties (e.g., ephedra).
  • Recent exposure therapy and/or Eye Movement Desensitization and Reprogramming (EMDR). These therapies must have been completed > 4 weeks before randomization.
  • Other psychotropic medications and/or maintenance psychotherapy at a stable dose for at least 4 weeks will not be exclusionary.

Trial locations and contacts

15 sites in 1 country.

15 sites in 1 country

United States15 sites

  • New Mexico VA Health Care System, Albuquerque

    Albuquerque, New Mexico, 87108-5153

  • WJB Dorn Veterans Hospital, Columbia

    Columbia, South Carolina, 29209

  • Atlanta VA Medical and Rehab Center, Decatur

    Decatur, Georgia, 30033

  • VA Medical Center, Durham

    Durham, North Carolina, 27705

  • VA Medical Center, Kansas City MO

    Kansas City, Missouri, 64128

  • VA Medical Center, Loma Linda

    Loma Linda, California, 92357

  • VA Medical Center, Long Beach

    Long Beach, California, 90822

  • Wlliam S. Middleton Memorial Veterans Hospital, Madison

    Madison, Wisconsin, 53705

  • VA Medical Center, Miami

    Miami, Florida, 33125

  • New York Harbor HCS

    New York, New York, 10010

  • VA Palo Alto Health Care System

    Palo Alto, California, 94304-1290

  • VA Medical Center, Providence

    Providence, Rhode Island, 02908

  • Salisbury VAMC

    Salisbury, North Carolina, 28144

  • VA Salt Lake City Health Care System, Salt Lake City

    Salt Lake City, Utah, 84148

  • VA Puget Sound Health Care System Seattle Division, Seattle, WA

    Seattle, Washington, 98108

Other trials in United States

About this study

Official title: CSP #563 - Prazosin and Combat Trauma PTSD (PACT)

Background: Posttraumatic stress disorder (PTSD) is a debilitating and disabling mental disorder that afflicts at least 25% of Veterans who have suffered life-threatening war zone trauma. Trauma-related nightmares and sleep disturbance are among the most treatment-resistant PTSD symptoms in Veterans. Increased responsiveness to central nervous system (CNS) norepinephrine (NE) contributes to the pathophysiology of overall PTSD and treatment-resistant nighttime symptoms. Placebo-controlled pilot studies demonstrate that the generically available CNS-active alpha-1 adrenoreceptor antagonist prazosin substantially reduces PTSD trauma nightmares and sleep disturbance and improves global clinical status (sense of well being and ability to function) in Veterans.

Objective: The primary objective is to demonstrate in a large multi-site placebo-controlled trial in Veterans with war zone trauma-induced PTSD that prazosin is efficacious for PTSD trauma nightmares, sleep disturbance, and global clinical status. A secondary objective is to demonstrate prazosin effectiveness for these outcome measures during clinically meaningful long-term (26 week) maintenance treatment of PTSD. The investigators will also address prazosin efficacy and long-term effectiveness for improving total PTSD symptoms, comorbid depression, quality of life, and physical functioning.

Read more

Methods: This 26 week randomized double-blind placebo-controlled study is designed to demonstrate both short term efficacy and long term effectiveness of prazosin for PTSD. The research design encompasses a shorter-term, more tightly controlled efficacy component and a longer-term, more .real world. effectiveness component. Three hundred twenty-six Veterans with war zone -related PTSD and persistent trauma nightmares will be randomized 1:1 to prazosin or placebo. Study drug will be increased using a flexible dose titration schedule based on clinical response and adverse effects to an optimum maintenance dose (1-20 mg/day). During the first 10 weeks of the study, participants will be randomized to prazosin or placebo. Previous psychotropic medications and/or psychotherapy will be maintained constant. Short term efficacy will be determined during the first 10 weeks. During the remaining 16 weeks of the 26 week trial, subjects will continue to receive stable-dose double-blind prazosin or placebo, but will have the option to receive additional psychotropic medications and/or psychotherapeutic interventions, as needed, per the judgment of the study Clinician Prescriber. It is hypothesized that prazosin will remain more clinically effective than placebo at the end of the 26-week trial, demonstrating that prazosin adds benefit over-and-above other treatments that are naturalistically administered by providers in a .real world. clinical setting.

Prazosin will be judged efficacious at 10 weeks if superior to placebo on all three primary outcome measures assessing trauma nightmares, sleep disturbance, and global clinical status: the Recurrent Distressing Dreams item of the Clinician Administered PTSD Scale (CAPS), the Pittsburgh Sleep Quality Index (PSQI), and the Clinical Global Impression of Change (CGIC). Secondary outcome measures will assess prazosin effects on total PTSD symptoms, depression, physical functioning, and quality of life. Adverse effects and cardiovascular measures, including supine and standing blood pressure (BP) and heart rate (HR) will be assessed.

Being tested
prazosin, placebo
Keywords
Combat Trauma, Post traumatic stress disorder, PTSD, Sleep Disturbance, Trauma-Related Nightmares
Medical subject headings
Stress Disorders, Post-Traumatic, Sleep Wake Disorders, Parasomnias

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • prazosinDrug

    Subjects will be titrated up to the optimum tolerated dose based on the Dosing Algorithm. Males and females will be titrated differently with females titrated slower and to a lower maximum daily dose. The first dose will be taken while the participant is in bed for the night to avoid orthostatic syncope, an uncommon but recognized "first dose" effect of prazosin or any alpha-1 antagonist if started at a high dose. As a further precaution, male subjects will be advised to sit on the toilet for urination at night during the first week of dose titration. The first dose effect is avoidable by starting treatment with a low dose (1 mg at bedtime) and then titrating the dose upward gradually.

  • placeboOther

    "sugar" pill

Study groups in NCT00532493
Study groupRoleWhat they receive
Prazosin GroupActive comparatorSubjects randomized to this arm will be on prazosin.
Receives: Drug: prazosin
Placebo GroupPlacebo comparatorSubjects randomized to this arm will be on placebo.
Receives: Other: placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. CAPS Recurrent Distressing Dreams Item

    Change from baseline in frequency and/or severity of combat trauma-related nightmares will be assessed by the CAPS Recurrent Distressing Dreams item. Possible range for Recurrent Distressing Dreams is 0-8. Higher score indicates more severe PTSD symptoms.

    Measured: This primary outcome measure was administered at baseline and week 10. The change of the 10-week from baseline was reported.

  2. Pittsburgh Sleep Quality Index (PSQI)

    Change from baseline in possible range for PSQI global score 0-21. Higher PSQI score indicates worse quality of sleep.

    Measured: This primary outcome measure was administered at baseline and week 10. The change of the 10-week from baseline was reported.

  3. Clinical Global Impression of Change (CGIC)

    Change from baseline in possible range for Clinical Global Impression of Change 1-7. As compared to baseline global condition, 1 is marked improvement, 2 is moderate improvement, 3 is minimal improvement, 4 is no change, 5 is minimal worsening, 6 is moderate worsening, and 7 is marked worsening.

    Measured: This primary outcome measure was administered at baseline and week 10. The change of the 10-week from baseline was reported.

Secondary outcomes (10)

  1. Pittsburgh Sleep Quality Index

    Change from baseline in possible range for PSQI global score 0-21. Higher PSQI score indicates worse quality of sleep.

    Measured: This secondary outcome measure was administered at baseline, 6, 10, 14, 18, 22 and 26 weeks (or early termination).

  2. CAPS Recurrent Distressing Dreams Item

    Change from baseline in frequency and/or severity of combat trauma-related nightmares will be assessed by the CAPS Recurrent Distressing Dreams item. Possible range for Recurrent Distressing Dreams is 0-8. Higher score indicates more severe PTSD symptoms.

    Measured: This secondary outcome measure was administered at baseline, 6, 10, 14, 18, 22 and 26 weeks (or early termination) to assess temporal course of changes in symptoms in response to prazosin or placebo.

  3. Clinical Global Impression of Change

    Change from baseline in possible range for Clinical Global Impression of Change (CGIC) 1-7. As compared to baseline global condition, 1 is marked improvement, 2 is moderate improvement, 3 is minimal improvement, 4 is no change, 5 is minimal worsening, 6 is moderate worsening, and 7 is marked worsening.

    Measured: This secondary outcome measure was administered at 6, 10, 14, 18, 22 and 26 weeks (or early termination).

  4. Total CAPS Score

    Change from baseline in possible range for CAPS total score is 0-136. Higher score indicates more severe PTSD symptoms.

    Measured: The total CAPS was administered at baseline, 6, 10, 18, and 26 weeks (or early termination).

  5. PTSD Checklist-Military Version (PCL-M) Score

    Change from baseline in possible range for PCL-M score 17-85. Higher PCL score indicates greater propensity for chronic and delayed PTSD.

    Measured: This secondary outcome was administered at baseline, 6, 10, 14, 18, 22 and 26 weeks to assess change in PTSD symptom severity.

  6. Patient Health Questionnaire-9 (PHQ9)

    Change from baseline in possible range for PHQ9 score is 0-27. Higher PHQ9 score indicates more severe depression.

    Measured: This secondary outcome measure was administered at baseline, 6, 10, 14, 18, 22 and 26 weeks (or early termination).

  7. SF-12 Physical Standardized Score (SF-12 PCS)

    Change from baseline in possible range for SF-12 PCS is 6-72. Higher SF-12 score indicates better level of health.

    Measured: This secondary outcome measure was administered at baseline, 6, 10, 14, 18, 22 and 26 weeks (or early termination).

  8. SF-12 Mental Standardized Score (SF-12 MCS)

    Change from baseline in possible range for SF-12 MCS is 5-76. Higher SF-12 score indicates better level of health.

    Measured: This secondary outcome measure was administered at baseline, 6, 10, 14, 18, 22 and 26 weeks (or early termination).

  9. Quality of Life Inventory (QOLI)

    Change from baseline in possible range for QOLI is -6 to 6. Higher QOLI indicates better satisfaction with life.

    Measured: This secondary outcome measure was administered at baseline, 6, 10, 14, 18, 22 and 26 weeks (or early termination).

  10. Alcohol Use Disorders Identification Test-Consumption (AUDIT-C)

    Change from baseline in possible range for Audit-C score is 0-12. Higher score indicates heavier use of alcohol. A score of >=4 for male and a score of >=3 for female meets the criteria for alcohol use disorders.

    Measured: This secondary outcome measure was administered at baseline, 6, 10, 14, 18, 22 and 26 weeks (or early termination).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Sep 2007 (estimated)
  2. Study start6 Jan 2010
  3. Primary completion28 Feb 2013
  4. Study completion31 May 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
304 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00532493
Sponsor's protocol ID
563
Acronym
PACT
Status last verified
Mar 2018
First submitted
18 Sep 2007
Last updated
1 May 2018
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Raskind MA, Peskind ER, Chow B, Harris C, Davis-Karim A, Holmes HA, Hart KL, McFall M, Mellman TA, Reist C, Romesser J, Rosenheck R, Shih MC, Stein MB, Swift R, Gleason T, Lu Y, Huang GD. Trial of Prazosin for Post-Traumatic Stress Disorder in Military Veterans. N Engl J Med. 2018 Feb 8;378(6):507-517. doi: 10.1056/NEJMoa1507598.

    PubMed 29414272

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing prazosin in people with PTSD and Sleep Disorders, run by VA Office of Research and Development at 15 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 May 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Jun 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

CAPS Recurrent Distressing Dreams Item (time frame: This primary outcome measure was administered at baseline and week 10. The change of the 10-week from baseline was reported.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00532493, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 May 2018.

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