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Predicting Responses to PTSD Treatment With Iris and Cardiovascular Tests (PREDICT)

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ClinicalTrials.gov Identifier: NCT03539614
Recruitment Status : Recruiting
First Posted : May 28, 2018
Last Update Posted : December 20, 2018
Sponsor:
Information provided by (Responsible Party):
VA Office of Research and Development

Brief Summary:

Posttraumatic stress disorder (PTSD) affects many individuals who experience a traumatic event. There are a variety of treatment options for PTSD, including psychotherapy (talk therapy) options, as well as medications, such as the drug prazosin. Each of the treatment options available is effective at significantly reducing the symptoms of PTSD in some, but not all, individuals with PTSD. However, investigators are not yet able to predict in advance who is likely to respond to which of the available treatments. Neither are the investigators able to explain what changes in the brain after exposure to a traumatic stressors, and why it results in persistent symptoms of PTSD for some people, but not for others.

In this study, the investigators are testing two things: First, is testing whether two simple, easy tests of how an individual's blood pressure changes with standing and how an individual's eye reacts to a pulse of light may be able to predict whether that person is likely respond to the medication prazosin for PTSD. Second, is testing whether those who have been exposed to a traumatic stress show differences in how their body regulates the response to the stress-signal noradrenaline.


Condition or disease Intervention/treatment Phase
Posttraumatic Stress Disorder Drug: Prazosin Drug: Placebo Phase 3

Detailed Description:
In this study, individuals will undergo an assessment that includes taking a history of their previous exposure to traumatic events, an assessment of current mental health symptoms including those associated with PTSD, and an assessment of physiologic measures, such as blood pressure and pupillary responses to light. For individuals who have current symptoms of PTSD and for whom use of the medication prazosin is a reasonable and safe option, a second phase of the study will be offered. In this second phase, how the individual's PTSD symptoms change when taking prazosin will be assessed. In addition, to test whether any changes are related to the prazosin itself or are part of a placebo effect, the individual will be randomly assigned to periods where he or she is taking a pill that looks like prazosin but is actual placebo (a pill with no active ingredient), and periods where he or she is taking a pill that looks the same but this time is actual prazosin.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: This study is a modified cross-over study, also called an aggregated N-of-1 study. Each participant who meets criteria for participation in and completes the treatment portion of the study will spend time on open-label prazosin, blinded prazosin, and placebo.
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Masking Description: During the portion of the study where participants are receiving either placebo or blinded prazosin, the participants, care providers, and outcomes assessors will all be blinded as to whether the participant is at that time receiving prazosin or placebo.
Primary Purpose: Treatment
Official Title: Noradrenergic Biomarkers in PTSD: Precision Medicine & Mechanisms
Actual Study Start Date : June 4, 2018
Estimated Primary Completion Date : April 3, 2023
Estimated Study Completion Date : June 5, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Open label, blinded discontinuation, prazosin, placebo
All participants in this study will begin with 8 weeks of active treatment (prazosin), followed by a 4 week "blinded discontinuation" block where they will take a capsule that will start out as active treatment (prazosin), but will at some point change to placebo. Following these phases of the study, participants will be randomized to two arms. In this first arm, participants will spend 4 weeks on active treatment (prazosin), followed by 4 weeks on placebo.
Drug: Prazosin
This is an antagonist of the alpha1 receptor for noradrenaline. It is FDA approved for the treatment of hypertension, and has also been used for benign prostatic hypertrophy (BPH). Most recently, it has been found to be helpful for symptoms of PTSD in some but not all participants.
Other Name: Minipress

Drug: Placebo
This is a capsule containing an inert substance, in order to provide blinding to participants and study staff of when participants are on active medication and when they are not during the later portions of the trial.

Experimental: Open label, blinded discontinuation, placebo, prazosin
All participants in this study will begin with 8 weeks of active treatment (prazosin), followed by a 4 week "blinded discontinuation" block where they will take a capsule that will start out as active treatment (prazosin), but will at some point change to placebo. Following these phases of the study, participants will be randomized to two arms. In this second arm, participants will spend 4 weeks on placebo, followed by 4 weeks on active treatment (prazosin).
Drug: Prazosin
This is an antagonist of the alpha1 receptor for noradrenaline. It is FDA approved for the treatment of hypertension, and has also been used for benign prostatic hypertrophy (BPH). Most recently, it has been found to be helpful for symptoms of PTSD in some but not all participants.
Other Name: Minipress

Drug: Placebo
This is a capsule containing an inert substance, in order to provide blinding to participants and study staff of when participants are on active medication and when they are not during the later portions of the trial.




Primary Outcome Measures :
  1. Change in total PTSD Checklist for DSM 5 (PCL5) score [ Time Frame: The PCL5 total score is assessed at baseline, during each stage of the study, and at the endpoint of the study. Thus, measurements will be scheduled to occur at the following time points, relative to the baseline visit: 0, 4, 8, 9-12, 16, and 20 weeks ]
    The PTSD Checklist for DSM 5 is a self-reported rating scale where an individual rates the severity of each symptom of PTSD on a likert scale. The ratings on individual items are summed to create a total score, which ranges from 0 to 80, with higher scores indicating more symptoms. The relationship between changes in participants' total PCL scores at different time points and prazosin exposure - and whether this relationship is moderated by baseline biomarker values - will be analyzed using a linear mixed effects model.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   21 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Veteran of the U.S. Armed Forces
  • Current diagnosis of PTSD (as documented in clinical chart and/or per participant report; a rule out diagnosis from a VA provider accompanied by a referral to the VA PTSD Outpatient Clinic (POC) will also be considered sufficient for inclusion)
  • Woman of childbearing potential must agree to abstain from sexual relations that could result in pregnancy or use an effective method of birth control acceptable to both participant and study clinician during the study. Men are not required to use contraception during the study.

Exclusion Criteria:

  • Psychiatric:

    • Any known diagnosis of a primary psychotic or major neurocognitive disorder, including schizophrenia, brief psychotic disorder, or Alzheimer's or other dementia, as well as bipolar type I
    • Current substance use disorder (except caffeine-related disorders, tobacco-related disorders, or cannabis intoxication) other than in remission for at least 3 months. The use of cannabis other than that meeting criteria for cannabis use disorder is not exclusionary. Use of cannabis will be documented.
    • 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 participant or others.

      • Note: Nonsuicidal depression comorbid with PTSD will not be exclusionary. Participants may continue in any concurrent psychotherapy or pharmacotherapy in which they are participating, other than pharmacotherapeutic agents specifically listed above. Participants with active suicidal ideation or with depression severe enough to require psychiatric hospitalization will be excluded.
  • Medical:

    • Significant bilateral visual loss (would preclude performing the PLR measurements)
    • Current pregnancy or lactation
    • Allergy or previous adverse reaction to prazosin or other alpha-1 antagonist
    • 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 > 20mmHg after two minutes standing or any drop accompanied by dizziness); autoimmune disorders; insulin-dependent diabetes
    • Chronic renal or hepatic failure, acute pancreatitis, Meniere's disease, benign positional vertigo, or narcolepsy
  • Medication / treatment:

    • Any use within the 7 days prior to baseline of prazosin, doxazosin, clonidine, guanfacine, trazodone, or nonbenzodiazepine hypnotics, and/or unwillingness to avoid these medications for the duration of the study
    • Use of avanafil (Stendra), 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, but will be allowed at 1/2 the usual starting dose following dose titration
    • Current use of nitrates, or of alternative medications or supplements with significant vasodilatory properties (e.g., nitrate containing supplements) Participants may also be excluded at the discretion of PI or study clinicians if they appear to be unsuitable for this research study for a reason not detailed here.

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): NCT03539614


Contacts
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Contact: Rebecca C Hendrickson, MD PhD (206) 277-5054 Rebecca.Hendrickson@va.gov
Contact: Hollie A Holmes, BA (206) 277-6207 hollie.holmes@va.gov

Locations
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United States, Washington
VA Puget Sound Health Care System Seattle Division, Seattle, WA Recruiting
Seattle, Washington, United States, 98108
Contact: Rebecca C Hendrickson, MD PhD    206-277-5054    Rebecca.Hendrickson@va.gov   
Contact: Hollie A Holmes, BA    (206) 277-6207    hollie.holmes@va.gov   
Principal Investigator: Rebecca C. Hendrickson, MD PhD         
Sponsors and Collaborators
VA Office of Research and Development
Investigators
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Principal Investigator: Rebecca C. Hendrickson, MD PhD VA Puget Sound Health Care System Seattle Division, Seattle, WA

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Responsible Party: VA Office of Research and Development
ClinicalTrials.gov Identifier: NCT03539614     History of Changes
Other Study ID Numbers: MHBB-003-17F
1IK2CX001774-01 ( U.S. NIH Grant/Contract )
First Posted: May 28, 2018    Key Record Dates
Last Update Posted: December 20, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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 VA Office of Research and Development:
Prazosin
Nightmares
N-of-1

Additional relevant MeSH terms:
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Stress Disorders, Post-Traumatic
Stress Disorders, Traumatic
Trauma and Stressor Related Disorders
Mental Disorders
Prazosin
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