Determining the Role of Sympathetic Activity in the Impact of Combat Injury on Sleep and Cardiovascular Outcomes

Study Overview
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Brief Summary
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The goal of this observational study is to learn about the long-term health of United States military service members who were injured during combat. The main questions it aims to examine are: How does the severity of a combat injury impact 1) cardiovascular risk, 2) the sympathetic nervous system and arrhythmias, 3) blood pressure, and 4) sleep disorders? Are self-reported mental health symptoms related to sympathetic nervous system hyperactivity, sleep disorders, and cardiovascular risk in combat-injured service members? This study will recruit from a sample of participants in another research study called the Wounded Warrior Recovery Project (WWRP) who 1) agreed to be contacted about future research studies and 2) have a record of a combat injury within the Injury Severity Score ranges required for this study. Participants will: Provide demographic information and a medical history review Visit a local laboratory for biometrics measurements and to provide blood and urine samples Wear an ambulatory electrocardiogram monitor for 24 hours per day for seven consecutive days Wear a home sleep test monitoring device for one night Wear a blood pressure monitor for 24 consecutive hours on the day after the home sleep test At the end of the study, participants will be asked to mail back the home sleep test and blood pressure monitors. Prepaid package materials will be provided.

Official Title
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Determining the Role of Sympathetic Activity in the Impact of Combat Injury on Sleep and Cardiovascular Outcomes (SPIRIT)

Conditions
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Arrythmia, Sympathetic Nervous System, Injury Traumatic, Hypertension, Cardiovascular Diseases, Sleep Disorder

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Enrolled in the Wounded Warrior Recovery Project (WWRP) and previously agreed to be contacted regarding future research Able to complete the informed consent process, be mailed study devices, and complete laboratory draws within the United States Age greater than or equal to 18 years Exclusion Criteria: No Injury Severity Score or 3 < Injury Severity Score < 15 Unable to complete the informed consent process, be mailed study devices, and complete laboratory draws within the United States Not enrolled in the WWRP or enrolled in the WWRP but did not agree to be contacted about future research

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Injury severity scored as severe<br>This group will include participants whose injury was scored as severe based on the recorded Injury Severity Score (ISS). Both cohorts will complete the same course of testing in this study. | |
| Injury severity scored as minimal<br>This group will include participants whose injury was scored as minimal based on the recorded Injury Severity Score (ISS). Both cohorts will complete the same course of testing in this study. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of arrhythmias | Readings from a 24-hour ambulatory electrocardiogram (ECG) monitor will be used to determine the frequency of arrhythmias. | 7 days of wear | 
| Frequency of atrial fibrillation | Readings from a 24-hour ambulatory electrocardiogram (ECG) monitor will be used to determine the frequency of atrial fibrillation. | 7 days of wear | 
| Frequency of atrial flutter | Readings from a 24-hour ambulatory electrocardiogram (ECG) monitor will be used to determine the frequency of atrial flutter. | 7 days of wear | 
| Density of premature ventricular contractions (PVCs) | Readings from a 24-hour ambulatory electrocardiogram (ECG) monitor will be used to determine the density of PVCs (percentage of total heartbeats that are PVCs). | 7 days of wear | 
| Frequency of ventricular tachycardia | Readings from a 24-hour ambulatory electrocardiogram (ECG) monitor will be used to determine the frequency of ventricular tachycardia. | 7 days of wear | 
| Heart rate | Readings from a 24-hour ambulatory electrocardiogram (ECG) monitor will be used to determine heart rate. | 7 days of wear | 
| Standard deviation of beat-to-beat intervals (SDNN) | Standard deviation of beat-to-beat intervals (SDNN) is a heart rate variability (HRV) time domain measure that will be automatically calculated for each 5-min epoch of the 24-hour ambulatory electrocardiogram (ECG) recording. | 7 days of wear | 
| Root mean square of successive differences (RMSSD) | Root mean square of successive differences (RMSSD) is a heart rate variability (HRV) time domain measure that will be automatically calculated for each 5-min epoch of the 24-hour ambulatory electrocardiogram (ECG) recording. | 7 days of wear | 
| Low frequency power | Low frequency power (LF, 0.04 - 0.15 Hz) is a heart rate variability (HRV) frequency domain measure that will be automatically calculated for each 5-min epoch of the 24-hour ambulatory electrocardiogram (ECG) recording. | 7 days of wear | 
| High frequency power | High frequency power (HF, 0.15 - 0.4 Hz) is a heart rate variability (HRV) frequency domain measure that will be automatically calculated for each 5-min epoch of the 24-hour ambulatory electrocardiogram (ECG) recording. | 7 days of wear | 
| Log-transformed QT variance (logQTv) | Log-transformed QT variance (logQTv) s a QT variability (QTV) measure that will be automatically calculated for each 5-min epoch of the 24-hour ambulatory electrocardiogram (ECG) recording. | 7 days of wear | 
| Beat-to-beat QT variability index (QTVI) | Beat-to-beat QT variability index (QTVI) is a QT variability (QTV) measure that will be automatically calculated for each 5-min epoch of the 24-hour ambulatory electrocardiogram (ECG) recording. | 7 days of wear | 
| Presence of obstructive sleep apnea | The presence of comorbid obstructive sleep apnea and/or nocturnal hypoxemia, will be evaluated with a home sleep study test device (HST) worn during the second or third study day | One night | 
| Presence of nocturnal hypoxemia | The presence of comorbid obstructive sleep apnea and/or nocturnal hypoxemia, will be evaluated with a home sleep study test device (HST) worn during the second or third study day | One night | 
| 24-hour ambulatory blood pressure monitor (ABPM) | Blood pressure (diastolic and systolic) will be assessed using a 24-hour ABPM worn during the 24-hour period following the HST. | 24 hours | 
| High sensitivity C-reactive protein (hs-CRP) | This inflammatory marker will be measured during laboratory testing. | Baseline | 
| Posttraumatic Stress Disorder Checklist for Diagnostic and Statistics Manual of Mental Disorder 5 (PCL-5) | The severity of Posttraumatic Stress Disorder (PTSD) symptoms will be assessed by the PCL-5 20-question survey. Total scores range from 0 - 80, with higher scores indicating greater PTSD symptom severity. | Baseline | 
| 8-item Patient Health Questionnaire depression scale (PHQ-8) | The severity of depressive symptoms will be measured by the eight-question PHQ-8 survey. Total scores range from 0 - 24, with with higher scores indicating greater depressive symptom severity. | Baseline | 
| Brief Dissociative Experience Scale (DES-B) | Severity of dissociative experiences will be assessed using the 8-item DES-B survey. Total scores range from 0 - 32, with with higher scores indicating greater dissociative experience severity. | Baseline | 
| Pittsburgh Sleep Quality Index (PSQI) | Participant-reported sleep characteristics will be assessed using the 19-item Pittsburgh Sleep Quality Index (PSQI). Total scores range from 0 - 21, with higher scores indicating worse sleep quality. | Baseline | 
| Epworth Sleepiness Scale (ESS) | Participant-reported sleep characteristics will be assessed using the 8-item Epworth Sleepiness Scale (ESS). Total scores range from 0 - 24, with higher scores indicating increased daytime sleepiness. | Baseline | 
| Insomnia Severity Index (ISI) | Participant-reported sleep characteristics will be assessed using the 7-item Insomnia Severity Index (ISI). Total scores range from 0 - 28, with higher scores indicating increased insomnia symptoms. | Baseline | 
| Berlin Sleep Questionnaire | Participant-reported sleep characteristics will be assessed using the 11-item Berlin Sleep Questionnaire. Scores will be calculated to determine if participants are High Risk or Low Risk for sleep apnea. | Baseline | 
| Body Mass Index | Height and weight will be measured during laboratory visit and combined to report BMI in kg/m^2. | Baseline | 
| Blood Pressure | Blood pressure (diastolic and systolic) will be recorded at the time of laboratory visit | Baseline | 
| Hemoglobin A1C (HBA1C) | This laboratory test will be used to assess overall health outcomes. | Baseline | 
| Alanine aminotransferase (ALT/SGPT) | This laboratory test will be measured as part of a comprehensive metabolic panel and will be used to assess overall health outcomes. | Baseline | 
| Albumin:globulin (A:G) ratio | This laboratory test will be measured as part of a comprehensive metabolic panel and will be used to assess overall health outcomes. | Baseline | 
| Albumin, serum | This laboratory test will be measured as part of a comprehensive metabolic panel and will be used to assess overall health outcomes. | Baseline | 
| Alkaline phosphatase, serum | This laboratory test will be measured as part of a comprehensive metabolic panel and will be used to assess overall health outcomes. | Baseline | 
| Aspartate aminotransferase (AST/SGOT) | This laboratory test will be measured as part of a comprehensive metabolic panel and will be used to assess overall health outcomes. | Baseline | 
| Bilirubin, total | This laboratory test will be measured as part of a comprehensive metabolic panel and will be used to assess overall health outcomes. | Baseline | 
| Blood urea nitrogen (BUN) | This laboratory test will be measured as part of a comprehensive metabolic panel and will be used to assess overall health outcomes. | Baseline | 
| Blood urea nitrogen (BUN):creatinine ratio | This laboratory test will be measured as part of a comprehensive metabolic panel and will be used to assess overall health outcomes. | Baseline | 
| Calcium, serum | This laboratory test will be measured as part of a comprehensive metabolic panel and will be used to assess overall health outcomes. | Baseline | 
| Carbon dioxide, total | This laboratory test will be measured as part of a comprehensive metabolic panel and will be used to assess overall health outcomes. | Baseline | 
| Chloride, serum | This laboratory test will be measured as part of a comprehensive metabolic panel and will be used to assess overall health outcomes. | Baseline | 
| Creatinine, serum | This laboratory test will be measured as part of a comprehensive metabolic panel and will be used to assess overall health outcomes. | Baseline | 
| Estimated glomerular filtration rate (eGFR) calculation | This laboratory test will be measured as part of a comprehensive metabolic panel and will be used to assess overall health outcomes. | Baseline | 
| Globulin, total | This laboratory test will be measured as part of a comprehensive metabolic panel and will be used to assess overall health outcomes. | Baseline | 
| Glucose, serum | This laboratory test will be measured as part of a comprehensive metabolic panel and will be used to assess overall health outcomes. | Baseline | 
| Potassium, serum | This laboratory test will be measured as part of a comprehensive metabolic panel and will be used to assess overall health outcomes. | Baseline | 
| Protein, total, serum | This laboratory test will be measured as part of a comprehensive metabolic panel and will be used to assess overall health outcomes. | Baseline | 
| Sodium, serum | This laboratory test will be measured as part of a comprehensive metabolic panel and will be used to assess overall health outcomes. | Baseline | 
| Cystatin C with estimated glomerular filtration rate (eGFR) | This laboratory test will be used to assess overall health outcomes. | Baseline | 
| Cholesterol, total | This laboratory test will be measured as part of a lipid panel and will be used to assess overall health outcomes. | Baseline | 
| High-density lipoprotein (HDL) cholesterol | This laboratory test will be measured as part of a lipid panel and will be used to assess overall health outcomes. | Baseline | 
| Low-density lipoprotein (LDL) cholesterol (calculation) | This laboratory test will be measured as part of a lipid panel and will be used to assess overall health outcomes. | Baseline | 
| Triglycerides | This laboratory test will be measured as part of a lipid panel and will be used to assess overall health outcomes. | Baseline | 
| Very low-density lipoprotein (VLDL) cholesterol (calculation) | This laboratory test will be measured as part of a lipid panel and will be used to assess overall health outcomes. | Baseline | 
| Albumin/creatinine ratio, random urine | This laboratory test will be used to assess overall health outcomes. | Baseline | 
| N-terminal pro b-type natriuretic peptide (NT-proBNP) | This laboratory test will be used to assess overall health outcomes. | Baseline |