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

NCT ID: NCT07071350

Last Updated: 2025-09-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Clinical Phase

PHASE2/PHASE3

Total Enrollment

148 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-09-02

Study Completion Date

2028-09-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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

See the medical conditions and disease areas that this research is targeting or investigating.

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

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

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.

Group Type EXPERIMENTAL

HRV Coherence Ratio

Intervention Type OTHER

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

Intervention Type BEHAVIORAL

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)

Intervention Type BEHAVIORAL

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

Intervention Type BEHAVIORAL

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)

Intervention Type BEHAVIORAL

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

Intervention Type BEHAVIORAL

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

Intervention Type OTHER

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)

Intervention Type BEHAVIORAL

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)

Intervention Type BEHAVIORAL

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)

Intervention Type OTHER

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.

Education

Psychoeducational treatment

Group Type EXPERIMENTAL

HRV Coherence Ratio

Intervention Type OTHER

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

Intervention Type BEHAVIORAL

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)

Intervention Type BEHAVIORAL

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

Intervention Type BEHAVIORAL

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)

Intervention Type BEHAVIORAL

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

Intervention Type BEHAVIORAL

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

Intervention Type OTHER

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)

Intervention Type BEHAVIORAL

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)

Intervention Type BEHAVIORAL

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.

Psychoeducational (Edu) Comparator Intervention

Intervention Type OTHER

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.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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.

Intervention Type OTHER

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.

Intervention Type 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.

Intervention Type 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.

Intervention Type 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.

Intervention Type 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

Intervention Type BEHAVIORAL

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.

Intervention Type OTHER

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.

Intervention Type 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.

Intervention Type BEHAVIORAL

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.

Intervention Type 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.

Intervention Type OTHER

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are 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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

United States Department of Defense

FED

Sponsor Role collaborator

Virginia Commonwealth University

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

James Burch

Role: PRINCIPAL_INVESTIGATOR

Virginia Commonwealth University

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Virginia Commonwealth University

Richmond, Virginia, United States

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

United States

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Brett Brooks

Role: CONTACT

(804) 827-9692

Jennifer Weggen

Role: CONTACT

8048279692

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Bret Brooks

Role: primary

804-627-9692

Jennifer Weggen

Role: backup

8046279692

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

HM20031279

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

SMART-CPT for PTSD/Concussion Implementation
NCT06995612 ENROLLING_BY_INVITATION NA
Vagal Nerve Stimulation in mTBI
NCT04437498 RECRUITING NA
Improving Cognitive Rehabilitation Outcomes
NCT07055633 NOT_YET_RECRUITING NA
Cognitive Training for PTSD
NCT03316196 COMPLETED NA