NCT07071350

Brief Summary

Many combat veterans (c-Vs), service members (SMs) and civilians with mild traumatic brain injury (mTBI, also termed concussion) suffer from persistent post-concussion symptoms (PPCS) that degrade physical and cognitive well-being and have been linked with early neurodegeneration. PPCS include somatosensory (e.g., headache, disturbed vision), vestibular (e.g., dizzy, clumsy), cognitive (e.g., executive function, memory) and affective symptoms (e.g., sleep disturbance, irritability, depression). A key pathological process that provokes and perpetuates PPCS is autonomic nervous system (ANS) dysfunction such as unremitting sympathetic nervous system activation that also exacerbates other pathology such as inflammation. ANS activity can be readily quantified by measuring heart rate variability (HRV), or the variation in heart rate over time, which serves as a valid index of both physiological and psychological health

Trial Health

77
On Track

Trial Health Score

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

Enrollment
148

participants targeted

Target at P75+ for phase_2

Timeline
29mo left

Started Sep 2025

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
recruiting

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 Progress23%
Sep 2025Sep 2028

First Submitted

Initial submission to the registry

June 26, 2025

Completed
21 days until next milestone

First Posted

Study publicly available on registry

July 17, 2025

Completed
2 months until next milestone

Study Start

First participant enrolled

September 2, 2025

Completed
3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2028

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2028

Last Updated

September 17, 2025

Status Verified

September 1, 2025

Enrollment Period

3 years

First QC Date

June 26, 2025

Last Update Submit

September 15, 2025

Conditions

Outcome Measures

Primary Outcomes (1)

  • Neurobehavioral Symptom Inventory (NSI)

    The Neurobehavioral Symptom Inventory (NSI) is a 22-item self-report questionnaire used to assess the severity of neurobehavioral symptoms following traumatic brain injury (TBI), particularly postconcussion symptoms. It's a widely used tool in TBI research and clinical evaluation by the Department of Defense and Department of Veterans Affairs. The total score ranges from 0 to 88, with higher scores indicating more severe post-concussive symptoms

    Baseline to end of study procedures (11 weeks)

Secondary Outcomes (5)

  • Heart Rate Variability Biofeedback (HRV-B)

    Baseline to end of study procedures (11 weeks)

  • NIH Toolbox Cognitive Battery

    Baseline to end of study procedures (11 weeks)

  • TBI-QoL Pain Interference Short-Form

    Baseline to end of study procedures (11 weeks)

  • Patient Health Questionnaire-9 (PHQ-9)

    Baseline to end of study procedures (11 weeks)

  • PCL-5 (PTSD Checklist for DSM-5)

    Baseline to end of study procedures (11 weeks)

Study Arms (2)

Heart rate variability biofeedback (HRV-B)

EXPERIMENTAL

Behavioral intervention using HRV biofeedback (HRV-B) to treat Persistent Post-Concussion Symptoms (PPCS) among adults, including Combat Veterans (c-Vs) and Service Members (SMs), with history of single or repeated mTBI from blast-related or other mechanism.

Other: HRV Coherence RatioBehavioral: NSIBehavioral: Pittsburgh Sleep Quality Index (PSQI)Behavioral: Quantitative Sleep MeasuresBehavioral: Patient Global Impression of Change (PGIC)Behavioral: Cognitive Performance/NIH Toolbox Cognitive BatteryOther: Pain Interference/TBI-QoL Pain Interference Short-FormBehavioral: Patient Health Questionnaire-9 (PHQ-9)Behavioral: PTSD Checklist for DSM-5 (PCL-5)Other: HRV Biofeedback (HRV-B)

Education

EXPERIMENTAL

Psychoeducational treatment

Other: HRV Coherence RatioBehavioral: NSIBehavioral: Pittsburgh Sleep Quality Index (PSQI)Behavioral: Quantitative Sleep MeasuresBehavioral: Patient Global Impression of Change (PGIC)Behavioral: Cognitive Performance/NIH Toolbox Cognitive BatteryOther: Pain Interference/TBI-QoL Pain Interference Short-FormBehavioral: Patient Health Questionnaire-9 (PHQ-9)Behavioral: PTSD Checklist for DSM-5 (PCL-5)Other: Psychoeducational (Edu) Comparator Intervention

Interventions

Evaluates autonomic function and the intervention process's efficacy, specifically resonance frequency breathing. The HRV Coherence Ratio will be quantified using a non-invasive procedure during resonance frequency breathing conditions and a standardized definition.

EducationHeart rate variability biofeedback (HRV-B)
NSIBEHAVIORAL

This inventory assesses the overall symptom burden, including post-concussion symptoms, on a 5-point scale. It is a well-established measure used by the Department of Defense (DoD) and VA and in mTBI outcome research at large, and includes 27 items that capture vestibular, somatosensory, cognitive, and affective symptoms.

EducationHeart rate variability biofeedback (HRV-B)

It includes seven components: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. Higher PSQI scores indicate poorer sleep quality.

EducationHeart rate variability biofeedback (HRV-B)

Measured using wrist actigraphy, which provides objective data on sleep parameters such as sleep latency, duration, efficiency, fragmentation, and wake time after sleep onset (WASO). Participants will wear the actigraphy monitors at baseline, post-training, and follow-up assessments.

EducationHeart rate variability biofeedback (HRV-B)

It evaluates patients' perceptions of clinically meaningful changes in their condition following the intervention. It is considered the gold standard for such assessments.

EducationHeart rate variability biofeedback (HRV-B)

Assessed using the NIH Toolbox Cognitive Battery, which measures executive function, episodic memory, working memory, processing speed, language, attention, and reading through a brief, computer-based test

EducationHeart rate variability biofeedback (HRV-B)

Evaluated using the TBI-QoL Pain Interference Short-Form, a 10-item questionnaire that measures the extent to which pain interferes with daily activities and overall quality of life. Each BPI-I item is scored from 0="Does not interfere" to 10="Completely interferes," and the scale score is the mean of the 7 items. Scores range from 0 to 10 with higher scores indicating greater pain interference.

EducationHeart rate variability biofeedback (HRV-B)

Assesses the severity of depressive symptoms over the past two weeks. Scores less than 5 almost always signified the absence of a depressive disorder; scores of 5 to 9 predominantly represented patients with either no depression or subthreshold (i.e., other) depression; scores of 10 to 14 represented a spectrum of patients; and scores of 15 or greater usually indicated major depression.

EducationHeart rate variability biofeedback (HRV-B)

The PCL-5 (PTSD Checklist for DSM-5) is a screening tool that assesses the presence and severity of PTSD symptoms according to DSM-5 criteria. It's not a diagnostic tool itself but helps clinicians determine if further evaluation is needed. Scores range from 0 to 80, with higher scores indicating more severe symptoms.

EducationHeart rate variability biofeedback (HRV-B)

participants will receive weekly biofeedback training over a six-week period. Each session includes approximately 30-40 minutes of biofeedback training where participants are affixed with HRV monitoring equipment. They will be guided to synchronize their heart rate variability (HRV) through slow diaphragmatic breathing and focusing on positive emotions. This process involves viewing real-time HRV patterns on a computer monitor, with coaching to help participants achieve resonant frequency breathing.

Heart rate variability biofeedback (HRV-B)

Six weekly meetings 30-40 minutes, viewing standardized educational content on concussion recovery. No information on breathing will be provided to participants in the Edu group.

Education

Eligibility Criteria

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

You may qualify if:

  • age 18 or older
  • History of military service
  • Self-Reported hx of 1 or more mild TBI
  • Most recent TBI more than 1 year ago
  • Significant Persistent Post-Concussion Symptom burden (Neurobehavioral Symptom Inventory \[NSI\] total score greater than or equal to 20).
  • Current Sleep Difficulties
  • Fluent English
  • Able to provide Informed Consent

You may not qualify if:

  • Any TBI with severity greater than mild (i.e., Moderate or Severe TBI defined as initial injury loss of consciousness (LOC) duration \>30 minutes, posttraumatic amnesia (PTA) duration \>24 hours, or traumatic hemorrhage on head computerized tomography (CT) and determined by the study investigator based on information gathered during administration of the study's validated TBI structured interview instrument.
  • Conditions or medications that can affect HRV measurement (pacemaker or an implant that stimulates your heart (e.g., cardioverter-defibrillator or ICD); heart transplant or heart surgery within the last year, including bypass or other surgery, but not including a stent)
  • Hx of stroke
  • Mental conditions that may impede adherence (e.g., dementia, psychotic disorder, panic disorder)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

RECRUITING

MeSH Terms

Conditions

Brain ConcussionStress Disorders, Post-Traumatic

Interventions

Patient Health Questionnaire

Condition Hierarchy (Ancestors)

Brain Injuries, TraumaticBrain InjuriesBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesCraniocerebral TraumaTrauma, Nervous SystemHead Injuries, ClosedWounds and InjuriesWounds, NonpenetratingStress Disorders, TraumaticTrauma and Stressor Related DisordersMental Disorders

Intervention Hierarchy (Ancestors)

Surveys and QuestionnairesData CollectionEpidemiologic MethodsInvestigative TechniquesPsychological TestsBehavioral Disciplines and ActivitiesHealth Care Evaluation MechanismsQuality of Health CareHealth Care Quality, Access, and EvaluationPublic HealthEnvironment and Public Health

Study Officials

  • James Burch

    Virginia Commonwealth University

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: This study, a randomized, controlled trial (RCT) of an easily implemented, mechanism-driven, behavioral intervention using HRV biofeedback (HRV-B) to treat PPCS among adults, including c-Vs and SMs, with history of single or repeated mTBI from blast-related or other mechanism.
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 26, 2025

First Posted

July 17, 2025

Study Start

September 2, 2025

Primary Completion (Estimated)

September 1, 2028

Study Completion (Estimated)

September 1, 2028

Last Updated

September 17, 2025

Record last verified: 2025-09

Data Sharing

IPD Sharing
Will not share

Locations