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

Primary Purpose

Posttraumatic Stress Disorder

Status
Recruiting
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Prazosin
Placebo
Sponsored by
VA Office of Research and Development
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Posttraumatic Stress Disorder focused on measuring Prazosin, Nightmares, N-of-1

Eligibility Criteria

21 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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
    • 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.

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Open label, blinded discontinuation, prazosin, placebo

Open label, blinded discontinuation, placebo, prazosin

Arm Description

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.

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).

Outcomes

Primary Outcome Measures

Change in total PTSD Checklist for DSM 5 (PCL5) score
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.

Secondary Outcome Measures

Full Information

First Posted
May 2, 2018
Last Updated
September 6, 2023
Sponsor
VA Office of Research and Development
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1. Study Identification

Unique Protocol Identification Number
NCT03539614
Brief Title
Predicting Responses to PTSD Treatment With Iris and Cardiovascular Tests
Acronym
PREDICT
Official Title
Noradrenergic Biomarkers in PTSD: Precision Medicine & Mechanisms
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 4, 2018 (Actual)
Primary Completion Date
February 29, 2024 (Anticipated)
Study Completion Date
February 29, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
VA Office of Research and Development

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

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 to 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Posttraumatic Stress Disorder
Keywords
Prazosin, Nightmares, N-of-1

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
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
ParticipantCare ProviderOutcomes 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.
Allocation
Randomized
Enrollment
70 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Open label, blinded discontinuation, prazosin, placebo
Arm Type
Experimental
Arm Description
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.
Arm Title
Open label, blinded discontinuation, placebo, prazosin
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Prazosin
Other Intervention Name(s)
Minipress
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
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 Measure Information:
Title
Change in total PTSD Checklist for DSM 5 (PCL5) score
Description
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.
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility 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 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Rebecca C Hendrickson, MD PhD
Phone
(206) 277-5054
Email
Rebecca.Hendrickson@va.gov
First Name & Middle Initial & Last Name or Official Title & Degree
Hollie A Holmes, BA
Phone
(206) 277-6207
Email
hollie.holmes@va.gov
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rebecca C. Hendrickson, MD PhD
Organizational Affiliation
VA Puget Sound Health Care System Seattle Division, Seattle, WA
Official's Role
Principal Investigator
Facility Information:
Facility Name
VA Puget Sound Health Care System Seattle Division, Seattle, WA
City
Seattle
State/Province
Washington
ZIP/Postal Code
98108-1532
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rebecca C Hendrickson, MD PhD
Phone
206-277-5054
Email
Rebecca.Hendrickson@va.gov
First Name & Middle Initial & Last Name & Degree
Hollie A Holmes, BA
Phone
(206) 277-6207
Email
hollie.holmes@va.gov
First Name & Middle Initial & Last Name & Degree
Rebecca C. Hendrickson, MD PhD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Predicting Responses to PTSD Treatment With Iris and Cardiovascular Tests

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