Recruiting
Phase 2
Phase 3

Observational Study

Sponsor:

Virginia Commonwealth University

Code:

NCT07071350

Conditions

Autonomic Nervous System Disease

Concussive Injury

Mild Traumatic Brain Injury

Post Traumatic Stress Disorder

Persistent Post Concussion Syndrome

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

HRV Coherence Ratio

NSI

Pittsburgh Sleep Quality Index (PSQI)

Quantitative Sleep Measures

Patient Global Impression of Change (PGIC)

Study Details

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

Conditions

Autonomic Nervous System Disease

Concussive Injury

Mild Traumatic Brain Injury

Post Traumatic Stress Disorder

Persistent Post Concussion Syndrome

Study ID

NCT07071350

Start date

Sep 2, 2025

Status verified date

Sep, 2025

Completion date

Sep, 2028

Anticipated

Primary completion date

Sep, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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)

Study Design

Enrollment

148 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Heart rate variability biofeedback (HRV-B)

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.

experimental: Education

Psychoeducational treatment

Interventions

HRV Coherence Ratio

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.

NSI

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.

Pittsburgh Sleep Quality Index (PSQI)

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.

Quantitative Sleep Measures

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.

Patient Global Impression of Change (PGIC)

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

Cognitive Performance/NIH Toolbox Cognitive Battery

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

Pain Interference/TBI-QoL Pain Interference Short-Form

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.

Patient Health Questionnaire-9 (PHQ-9)

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.

PTSD Checklist for DSM-5 (PCL-5)

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.

HRV 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.

Psychoeducational (Edu) Comparator Intervention

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.

Primary outcome measure

  • Neurobehavioral Symptom Inventory (NSI) [ Time Frame: Baseline to end of study procedures (11 weeks) ]

Central Contacts and Locations

Central contacts

Brett Brooks

(804) 827-9692bret.brooks@vcuhealth.org

Jennifer Weggen

8048279692weggenj@vcu.edu

Locations

Virginia Commonwealth University

Recruiting

Richmond, Virginia, United States, 23298

Contacts

Bret Brooks

804-627-9692brooksbm2@vcu.edu

Jennifer Weggen

8046279692weggenj@vcu.edu

Principal Investigator:

James Burch

More Information

Sponsor

Virginia Commonwealth University

Last update posted

Sep 17, 2025

Last verified

Sep, 2025

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-14. This information was provided to ClinicalTrials.gov by Virginia Commonwealth University on 2025-09-17.