A Policy Relevant US Trauma Care System Pragmatic Trial for PTSD and Comorbidity (TSOS6)

The overarching goal of this UH2-UH3 proposal is to work with the NIH Health Care Systems Research Collaboratory to develop and implement a large scale, cluster randomized pragmatic clinical trial demonstration project that directly informs national trauma care system policy targeting injured patients with presentations of Posttraumatic Stress Disorder (PTSD) and related comorbidity. Each year in the United States (US), over 30 million individuals present to trauma centers, emergency departments, and other acute care medical settings for the treatment of physical injuries. Multiple chronic conditions including enduring PTSD, alcohol and drug use problems, depression and associated suicidal ideation, pain and somatic symptom amplification, and chronic medical conditions (e.g., hypertension, coronary artery disease, diabetes, and pulmonary diseases) are endemic among physical trauma survivors with and without traumatic brain injuries (TBI). Evidence-based, collaborative care/care management treatment models for PTSD and related comorbidities exist. These care management models have the potential to be flexibly implemented in order to prevent the development of chronic PTSD and depressive symptoms, alcohol use problems, and enduring physical disability in survivors of both TBI and non-TBI injuries; care management models may also be effective in mitigating the impact of the acute injury event on symptom exacerbations in the large subpopulation of injury survivors who already carry a substantial pre-injury burden of multiple chronic medical conditions.

Study Overview

• Status: Completed
• Conditions: Substance-Related Disorders; Depression; Alcohol-Related Disorders; Quality of Life; Pain; Brain Injuries; Chronic Disease; Suicidal Ideation; Mild Cognitive Impairment; Posttraumatic Stress Disorder; Wounds and Injury
• Intervention / Treatment: Behavioral: Motivational Interviewing; Behavioral: Cognitive Behavioral Therapy Elements; Behavioral: Care Management; Drug: Fluoxetine; Drug: Fluvoxamine; Drug: Paroxetine; Drug: Sertraline; Drug: Citalopram; Drug: Venlafaxine; Drug: Duloxetine; Drug: Mirtazapine; Drug: Diphenhydramine; Drug: Trazodone; Drug: Prazosin

Detailed Description

Primary Aims and Hypotheses

The primary aim of the UH3 period is to conduct a pragmatic randomized effectiveness trial of a collaborative care intervention targeting PTSD and comorbid conditions after acute care injury hospitalization. The investigation aims to determine if injured patients receiving the collaborative care intervention demonstrate significant reductions in PTSD symptoms when compared to control patients receiving care as usual. The study also aims to determine if the intervention patients when compared to control patients will demonstrate significant reductions in depressive symptoms, suicidal ideation, and alcohol use problems, and improvements in physical function. The primary hypothesis is that the intervention group when compared to the control group will demonstrate significant reductions in PTSD symptoms over the course of the year after injury. Secondary hypotheses are that intervention patients when compared to control patients will demonstrate, significant reductions in depressive symptoms, significant reductions in alcohol use problems, and improved post-injury physical function.

A Priori Secondary Analyses

The study team hypothesizes that a subgroup of patients will have persistent PTSD symptoms that will not remit over the longitudinal course of the investigation, regardless of randomization to intervention or control group conditions. The study team also anticipates that readily identifiable baseline clinical, injury and demographic characteristics will be associated with persistent PTSD symptoms over time (e.g., higher PTSD symptom levels, greater pre-injury trauma exposure, intentional injury including firearm related injury mechanisms and other characteristics such as unemployment, as well as other baseline factors). Derived from previous randomized clinical trials, a cumulative burden index has been developed from these baseline characteristics and will be adapted for the current investigation. The study team proposes a series of secondary analyses that adjust for and stratify by baseline characteristics that put patients at risk for persistent symptoms. It is hypothesized that these secondary analyses will identify a subgroup of intervention patients who are not at risk for persistent symptoms and who will demonstrate clinically and statistically significant treatment responses when compared to patients with similar baseline characteristics in the control condition. The study team also hypothesizes that the treatment effects will be greatest at the 1-6 month post-injury time points that are temporally correlated with the period of active intervention.

• Study Type: Interventional
• Enrollment (Actual): 635
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85251
      • Honor Health
  • California
    • Beverly Hills, California, United States, 90211
      • Cedars Sinai
    • Sacramento, California, United States, 95816
      • U.C. Davis
    • San Jose, California, United States, 95128
      • Santa Clara Valley Medical Center
    • Torrance, California, United States, 90509
      • U.C.L.A. Harbor
  • Connecticut
    • Hartford, Connecticut, United States, 06102
      • Hartford Hospital
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Georgia Regents
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Eskenazi Health
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Louisiana State University
  • Minnesota
    • Saint Paul, Minnesota, United States, 55101
      • Regions Hospital
  • New York
    • Bronx, New York, United States, 10461
      • Jacobi Medical Center
    • Rochester, New York, United States, 14642
      • University of Rochester
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
    • Columbus, Ohio, United States, 43210
      • Ohio State University
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center
    • Dallas, Texas, United States, 75204
      • Baylor Health Care System
    • Galveston, Texas, United States, 77555
      • University of Texas Medical Branch at Galveston
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • The University of Utah
  • Vermont
    • Burlington, Vermont, United States, 05405
      • The University of Vermont
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • Inova Trauma Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53715
      • The University of Wisconsin Madison

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient currently admitted to inpatient/emergency department for a traumatic injury

Exclusion Criteria:

• Non-English speaking
• Self-inflicted injury
• Actively psychotic
• Incarcerated or in custody
• Less than 35 on PTSD Checklist
• Less than 3 items on PTSD medical record screen
• Less than 2 pieces of contact information

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Intervention; The intervention aims to prevent the development of chronic PTSD and depressive symptoms, alcohol use problems, and enduring physical disability in survivors of both traumatic brain injury(TBI) and non-TBI injuries. The intervention utilizes a computerized decision support tool to flexibly target these multiple conditions including and includes care management, motivational interviewing, cognitive behavioral therapy elements, psychotropic drugs, and psychotherapy elements.	Behavioral: Motivational Interviewing; Behavioral: Cognitive Behavioral Therapy Elements; Behavioral: Care Management; Drug: Fluoxetine; Anti-depressant; Drug: Fluvoxamine; Anti-depressant; Drug: Paroxetine; Anti-depressant; Drug: Sertraline; Anti-depressant; Drug: Citalopram; Anti-depressant; Drug: Venlafaxine; Anti-depressant; Drug: Duloxetine; Anti-depressant; Drug: Mirtazapine; Anti-depressant; Drug: Diphenhydramine; Sleep medication; Drug: Trazodone; Sleep medication; Drug: Prazosin; Sleep medication
NO_INTERVENTION: Usual Care; Enhanced standard care practices will be administered to this arm. This enhancement is sharing distressing emotional symptoms at recruitment with the attending nursing staff to address with patient subject.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline PTSD Checklist- Civilian (PCL-C) Over the Course of the Year After Injury	The investigators will use the PTSD Checklist - Civilian (PCL-C). The scoring of the scale ranges from a minimum of 17 to a maximum of 85, with higher scores indicating a worse outcome. The measure can also provide a rating of symptoms consistent with a diagnosis of PTSD.	Baseline, 3-month, 6-month, 12-month
Change From Baseline Patient Health Questionnaire 9 Item Depression Scale Over the Course of the Year After Injury	The investigators will use the Patient Health Questionnaire 9-item Depression Scale (PHQ-9). The scoring of the scale ranges from a minimum of 0 to a maximum of 27, with higher scores indicating a worse outcome.	Baseline, 3-month, 6-month, 12-month
Change From Baseline Alcohol Use Disorders Identification Over the Course of the Year After Injury	The investigators will use the Alcohol Use Disorders Identification Test (AUDIT) as a continuous measure. The 10-item scale score ranges from 0-40, with higher values indicating a worse outcome.	Baseline, 3-month, 6-month, 12-month
Change From Baseline Short Form (SF)-12/36 Physical Function Over the Course of the Year After Injury	The investigators used the Medical Outcomes Study Short Form healthy survey (MOS SF-12/36) physical components summary to assess physical function. The minimum and maximum scores are 0-100 with higher scores representing a better outcome.	Baseline, 3-month, 6-month, 12-month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Suicidal Ideation	Item 9 of the Patient Health Questionnaire 9-item (PHQ-9) scale assesses suicidal ideation. It is scored from 0 to 3, with a score of 1 or greater indicating a patient has suicidal ideation. Participants with a PHQ-9 item 9 score of greater than or equal to 1 are reported for this outcome.	Baseline, 3-month, 6-month, 12-month
Number of Participants Endorsing a Single Item That Assesses Opioid Use	Single items that assess non-prescribed opioid use. Single item self-report dichotomized as none versus at least monthly use.	Baseline, 3-month, 6-month, 12-month
Cognitive Impairment Scale	The investigators will use the National Study on the Costs and Outcomes of Trauma (NSCOT) Cognitive Screen, a 4 - Item Traumatic Brain Injury / Post-concussive Symptom Screen. The scoring of the scale ranges from a minimum of 4 to a maximum of 20, with lower scores indicating a worse outcome.	Baseline, 3-month, 6-month, 12-month
Brief Pain Inventory	A brief measure scored on a 0 to 10 scale to assess a patient's pain, with a higher score indicating more severe pain; a score of 0 indicates no pain and a score of 10 indicates very severe pain.	Baseline, 3-month, 6-month, 12-month
SF-36 Quality of Life	The SF-36 assess quality of life domains that span emotional health, overall health status, and role function; a score of 100 indicates perfect health and a score of 0 indicates extremely poor health.	Baseline, 3-month, 6-month, 12-month
TSOS Patient Satisfaction: Overall Health Care	Satisfaction with health care was rated on a scale of 1 to 5, with 1 indicating very dissatisfied and 5 indicating very satisfied.	Baseline, 3-month, 6-month, 12-month
Number of Participants Endorsing a Single Item That Assesses Stimulant Use	Single items that assess non-prescribed stimulant use. Single item self-report dichotomized as none versus at least monthly use.	Baseline, 3-month, 6-month, 12-month
Number of Participants Endorsing a Single Item That Assesses Marijuana Use	Single items that assess marijuana use. Single item self-report dichotomized as none versus at least monthly use.	Baseline, 3-month, 6-month, 12-month
TSOS Patient Satisfaction: Mental Health Care	Satisfaction with mental health care was rated on a scale of 1 to 5, with 1 indicating very dissatisfied and 5 indicating very satisfied.	Baseline, 3 Month, 6 Month, 12 Month

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA); National Institute of Mental Health (NIMH); National Institutes of Health (NIH)

Publications and helpful links

General Publications

• Nguyen J, Whiteside LK, Bulger EM, Veach L, Moloney K, Russo J, Nehra D, Wang J, Zatzick DF. Post-traumatic stress disorder (PTSD) symptoms and alcohol and drug use comorbidity at 25 US level I trauma centers. Trauma Surg Acute Care Open. 2022 Aug 4;7(1):e000913. doi: 10.1136/tsaco-2022-000913. eCollection 2022.
• Engstrom A, Moloney K, Nguyen J, Parker L, Roberts M, Moodliar R, Russo J, Wang J, Scheuer H, Zatzick D. A Pragmatic Clinical Trial Approach to Assessing and Monitoring Suicidal Ideation: Results from A National US Trauma Care System Study. Psychiatry. 2022 Spring;85(1):13-29. doi: 10.1080/00332747.2021.1991200. Epub 2021 Dec 21.
• Nehra D, Bulger EM, Maier RV, Moloney KE, Russo J, Wang J, Anderson K, Zatzick DF. A Prospective US National Trauma Center Study of Firearm Injury Survivors Weapon Carriage and Posttraumatic Stress Disorder Symptoms. Ann Surg. 2021 Oct 1;274(4):e364-e369. doi: 10.1097/SLA.0000000000005043.
• Zatzick D, Jurkovich G, Heagerty P, Russo J, Darnell D, Parker L, Roberts MK, Moodliar R, Engstrom A, Wang J, Bulger E, Whiteside L, Nehra D, Palinkas LA, Moloney K, Maier R. Stepped Collaborative Care Targeting Posttraumatic Stress Disorder Symptoms and Comorbidity for US Trauma Care Systems: A Randomized Clinical Trial. JAMA Surg. 2021 May 1;156(5):430-474. doi: 10.1001/jamasurg.2021.0131. Erratum In: JAMA Surg. 2021 Dec 8;:
• Zatzick DF, Russo J, Darnell D, Chambers DA, Palinkas L, Van Eaton E, Wang J, Ingraham LM, Guiney R, Heagerty P, Comstock B, Whiteside LK, Jurkovich G. An effectiveness-implementation hybrid trial study protocol targeting posttraumatic stress disorder and comorbidity. Implement Sci. 2016 Apr 30;11:58. doi: 10.1186/s13012-016-0424-4.

Study record dates

Study Major Dates

• Study Start: October 1, 2015
• Primary Completion (ACTUAL): November 1, 2019
• Study Completion (ACTUAL): November 1, 2019

Study Registration Dates

• First Submitted: July 27, 2015
• First Submitted That Met QC Criteria: January 11, 2016
• First Posted (ESTIMATE): January 14, 2016

Study Record Updates

• Last Update Posted (ACTUAL): July 2, 2021
• Last Update Submitted That Met QC Criteria: July 1, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Chemically-Induced Disorders; Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Disease Attributes; Craniocerebral Trauma; Trauma, Nervous System; Trauma and Stressor Related Disorders; Cognition Disorders; Self-Injurious Behavior; Stress Disorders, Traumatic; Suicide; Substance-Related Disorders; Disease; Brain Injuries; Stress Disorders, Post-Traumatic; Wounds and Injuries; Cognitive Dysfunction; Chronic Disease; Suicidal Ideation; Alcohol-Related Disorders; Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anesthetics; Antiemetics; Gastrointestinal Agents; Dermatologic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Dopamine Agents; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Hypnotics and Sedatives; Anti-Anxiety Agents; Cytochrome P-450 Enzyme Inhibitors; Antidepressive Agents, Second-Generation; Serotonin and Noradrenaline Reuptake Inhibitors; Anesthetics, Local; Cytochrome P-450 CYP2D6 Inhibitors; Serotonin 5-HT3 Receptor Antagonists; Anti-Allergic Agents; Sleep Aids, Pharmaceutical; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Antipruritics; Cytochrome P-450 CYP1A2 Inhibitors; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Adrenergic alpha-2 Receptor Antagonists; Cytochrome P-450 CYP2C19 Inhibitors; Sertraline; Duloxetine Hydrochloride; Citalopram; Paroxetine; Diphenhydramine; Promethazine; Venlafaxine Hydrochloride; Mirtazapine; Fluoxetine; Fluvoxamine; Prazosin; Trazodone
• Other Study ID Numbers: 20150987; UH3MH106338 (NIH)