NCT07071350

Randomized Controlled Trial of Treatment to Optimize Heart Rate Variability for Persistent Post-Concussion Symptoms

• Status: Recruiting
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 148 (estimated)
• Sponsor: Virginia Commonwealth University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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

Detailed description

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. Specifically, we study an intervention for persons with PPCS that promotes sustained functional recovery during the chronic phase of injury, which addresses psychological health and cognitive functioning, and has the potential to address neurodegenerative processes associated with TBI and treat co-occurring TBI and psychological health conditions. Importantly, the intervention is non-invasive, rapidly deployable, and is based on the pathophysiology and a theoretical mechanism of PPCS. Secondarily, this project also has the potential as a more generalized solution to increase readiness and psychological resilience in individuals, small teams, families, and communities to ameliorate the potential negative impacts of specific military and life stressors.

Conditions

• Autonomic Nervous System Disease
• Concussive Injury
• Mild Traumatic Brain Injury
• Post Traumatic Stress Disorder
• Persistent Post Concussion Syndrome

Interventions

Type	Name	Description
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.

Timeline

• Start date: 2025-09-02
• Primary completion: 2028-09-01
• Completion: 2028-09-01
• First posted: 2025-07-17
• Last updated: 2025-09-17

Locations

1 site across 1 country: United States