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

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

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Cardiovascular Diseases; Hypertension; Sleep Disorder; Arrythmia; Injury Traumatic; Sympathetic Nervous System

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20814
      • Uniformed Services University of the Health Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Wounded Warrior Recovery Project participants who 1) agreed to be contacted about future research studies and 2) have a record of injury within the established Injury Severity Score cutoffs for this study

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Injury severity scored as "severe"; 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"; 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?

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

Collaborators and Investigators

• Sponsor: Uniformed Services University of the Health Sciences
• Collaborators: Naval Health Research Center
• Investigators: Principal Investigator: Ian Stewart, MD, Uniformed Services University of the Health Sciences

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2024
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): April 1, 2025

Study Registration Dates

• First Submitted: June 27, 2023
• First Submitted That Met QC Criteria: July 24, 2023
• First Posted (Actual): August 2, 2023

Study Record Updates

• Last Update Posted (Actual): April 3, 2024
• Last Update Submitted That Met QC Criteria: April 1, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Cardiovascular Diseases; Sleep Wake Disorders; Wounds and Injuries
• Other Study ID Numbers: USUHS.2022-110

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No