NCT07071350 · Virginia Commonwealth University
Randomized Controlled Trial of Treatment to Optimize Heart Rate Variability for Persistent Post-Concussion Symptoms
What this study is about
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.
View original scientific description
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.
Interventions
OTHER
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.
BEHAVIORAL
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.
BEHAVIORAL
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.
BEHAVIORAL
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.
BEHAVIORAL
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.
BEHAVIORAL
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
OTHER
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.
BEHAVIORAL
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.
BEHAVIORAL
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.
OTHER
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.
OTHER
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 measures
Neurobehavioral Symptom Inventory (NSI)
Time frame: Baseline to end of study procedures (11 weeks)
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
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
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)
Where
- Richmond, Virginia
Collaborators
United States Department of Defense
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Sep 22, 2026 · Source of record for eligibility and locations