NCT05971433

Brief Summary

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.

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
200

participants targeted

Target at P75+ for all trials

Timeline
4mo left

Started Apr 2024

Typical duration for all trials

Geographic Reach
1 country

1 active site

Status
enrolling by invitation

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress84%
Apr 2024Oct 2026

First Submitted

Initial submission to the registry

June 27, 2023

Completed
1 month until next milestone

First Posted

Study publicly available on registry

August 2, 2023

Completed
8 months until next milestone

Study Start

First participant enrolled

April 1, 2024

Completed
2.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2026

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2026

Last Updated

May 5, 2026

Status Verified

April 1, 2026

Enrollment Period

2.5 years

First QC Date

June 27, 2023

Last Update Submit

May 2, 2026

Conditions

HypertensionCardiovascular DiseasesSleep DisorderArrythmiaSympathetic Nervous SystemInjury Traumatic

Outcome Measures

Primary Outcomes (52)

  • 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

Study Arms (2)

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.

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-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

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Uniformed Services University of the Health Sciences

Bethesda, Maryland, 20814, United States

Location

Related Publications (1)

  • Walker LE, Jurick SM, Thomas V, Arnold T, Elisman K, Kalra S, Mains A, Rioux S, Galarneau M, McCabe C, Lavender JM, Collen J, Haigney MC, Solhjoo S, Stewart IJ. A study protocol for determining the role of Sympathetic activity in Post-injury outcomes: Impact on sleep and caRdiovascular health InvesTigation (SPIRIT). PLoS One. 2025 Jul 17;20(7):e0321035. doi: 10.1371/journal.pone.0321035. eCollection 2025.

    PMID: 40674309DERIVED

MeSH Terms

Conditions

HypertensionCardiovascular DiseasesSleep Wake DisordersArrhythmias, CardiacWounds and Injuries

Condition Hierarchy (Ancestors)

Vascular DiseasesNervous System DiseasesNeurologic ManifestationsSigns and SymptomsPathological Conditions, Signs and SymptomsMental DisordersHeart DiseasesPathologic Processes

Study Officials

  • Ian Stewart, MD

    Uniformed Services University of the Health Sciences

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
CROSS SECTIONAL
Sponsor Type
FED
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor of Medicine; Director, Division of Nephrology

Study Record Dates

First Submitted

June 27, 2023

First Posted

August 2, 2023

Study Start

April 1, 2024

Primary Completion (Estimated)

October 1, 2026

Study Completion (Estimated)

October 1, 2026

Last Updated

May 5, 2026

Record last verified: 2026-04

Data Sharing

IPD Sharing
Will not share

Locations

US(1)