Neurofeedback Impact on Veterans With mTBI — NFBVETmTBI  

Chronic Insomnia Clinical Trial

Official title: Neurofeedback Impact on Chronic Headache, Sleep and Attention Disorders Experienced by Veterans With Mild Traumatic Brain Injury.

Status Recruiting

Clinical Trial Summary

This study will evaluate neurofeedback (NFB) training as a low risk, non-invasive, effective treatment for Veterans diagnosed with mild traumatic brain injury (mTBI) and experiencing chronic post-concussive symptoms (PCSs). It is being funded by the Department of Veterans Affairs. Doing this study will help to determine if NFB will reduce chronic headaches and enhance sleep, attention and quality of life in Veterans with mTBI.

NFB is like other biofeedback processes in which information about a person's specific body functioning is made known to the person through a special computer program, which can help that person make the specific body function work better through training. This type of training is usually fun and easy with the help of a coach and a computer. Nothing is ever put into a person's body with biofeedback and it is natural and safe. When a person becomes focused, calm and alert while training on an NFB system, the computer will recognize this and let the trainee know by automatically displaying on the computer screen the positive progression of the game they are playing, such as the plane moving forward or a flower opening. The brain really likes to be in this pattern and when it is happening, people feel good. As a result, any discomforts, like headaches or insomnia, experienced may decrease.

After learning about the study, Veterans who agree to participate will be randomly placed into one of two groups, either an intervention group (who will receive NFB) or a control group (who will receive only usual care plus once a week 15-minute calls on health topics). Veterans will have an equal chance of being in either group. Those placed in the control, will also receive NFB after completion of the control group activities. Veterans who are placed in the intervention or delayed intervention group will receive NFB up to 5 times a week, but usually 3 times a week for a total of 20 sessions. Each session is an hour long.

Both the intervention and control group will participate in four assessment sessions (lasting up to 2 1/2 hours each) that involve completing 12 questionnaires and a 20-minute attention evaluation. The assessment sessions will occur at the beginning of the study, at 4-6 weeks, at 8-10 weeks, and 2-months later. The participant will receive financial compensation for taking the baseline assessment, 4-6 week, 8-10-week assessments, and for the 2-month follow-up assessment. A participant will receive financial compensation for gas, time and valet parking for each intervention and assessment session. Participation in this research will last about 4 months for those in the intervention and 8 months for those in the delayed intervention group. All participants will receive the NFB treatment by the end of the study.

A person who participates in this study may experience a reduction in his or her chronic headaches, and an enhancement of sleep, attention and quality of life. There may be a worsening of symptoms until the individualized training plan for a person can be identified. During an NFB session, brief moments, lasting only seconds or minutes, of dizziness while sitting, muscle tension, or tingling may be experienced. Most people feel relaxed and calm during and after NFB training.

This project will be an important step towards a broader implementation of an evidence-based treatment solution for Veterans experiencing chronic headaches, insomnia and attention disorders. The experience of these chronic symptoms can lead to debilitation in all areas of Veterans' lives. This project will provide evidence for the use of NFB with Veterans to alleviate their chronic symptoms and enhance their quality of life. If supported, NFB will offer the investigators' Veterans an effective and non-invasive treatment option. NFB is a patient focused intervention that enables Veterans the opportunity for self-health management.

Clinical Trial Description

BACKGROUND AND SIGNIFICANCE Veterans, while serving in Iraq and Afghanistan, may have had exposure to improvised explosive devices (IEDs). These blast exposures resulted in the "signature injury" of these operations, traumatic brain injuries (TBIs). The over-pressurization shock waves emitted from the blast causes human brain injury, which may be considered a mixed mechanism injury event; involving both a focal (direct impact of brain's surface on the bony protuberances of the skull) and diffuse injury (stretching and twisting of axons and blood vessels by shearing forces). The blast event injury is generally followed by a secondary, longer duration injury related to the activation of molecular and biochemical responses stemming from the initial blast injury. This secondary injury was once thought of as self-limiting (hours or days post- injury); however recent findings suggest that the abnormal brain signaling and inflammatory processes last much longer and can lead to long term symptoms. In addition, these processes can cause a disruption of normal brain connectivity, abnormal electrical brain waves and patterns, as well as disruptions of intra- and interhemispheric communication, which can persist from acute to chronic stages in many patients. The changes in the brain stemming from TBI may persist and even progress in the long run. Recent evidence has confirmed the long-suspected association between TBI and the development of neurodegenerative diseases later in life. The majority of blast related injuries are not detectable by current neuroimaging strategies, e.g. computed tomography (CT) or magnetic resonance imaging (MRI) but rely on self-report of blast exposure and its effects for TBI diagnosis.

The prevalence rate of TBI for Service Members (SMs) involved in these operations is estimated to be 20% with about 80% of these injuries considered mild(m)TBI. It has been suggested that the actual rate of mTBI may be under-reported (up to 50%) since cognitive disturbances associated with TBI may impact SM's memory of the blast experience and SMs who are caught up in the battle may not report blast exposures. The residual effects of mTBI can also be unrecognized, undocumented, under reported, misinterpreted or misdiagnosed as only psychological. Most SMs, who experienced mTBI, appear to recover within hours or days, however for a significant number, estimated at 23-48%, symptoms persist and may persist for many years post injury.

SMs and Veterans with mTBI can fatigue easily and have disordered sleep, headache, dizziness, irritability or aggression on little or no provocation, as well as experience anxiety, depression, or affective lability and changes in personality and cognitive functioning. When these symptoms persist, they can negatively impact Veterans' self-rated health, occupational status (ability to return to work, school) social functioning (relationships, participation in groups) and quality of life.

Developing and implementing strategies to reduce the persistent symptoms associated with mTBI is of critical importance. Veterans diagnosed with mTBI and experiencing PCSs present growing treatment challenges to the healthcare system due to limited or suboptimal treatment options. Currently, treatment for PCSs is symptom-focused. For instance, Veterans with migraine headaches associated with mTBIs are often treated with abortive agents (i.e. Triptans) and preventive medications (i.e. anticonvulsants and tricyclics). Cognitive dysfunction and insomnia are treated with cognitive rehabilitation programs, cognitive behavior therapy (CBT), occupational therapy, and medications (i.e., hypnotics for insomnia). Symptom management is just that, applying a temporary fix on symptoms or addressing concerns one at a time. While cognitive rehabilitation and psychological support are widely used to treat mTBI PCSs, neither has been shown to be effective in addressing the core brain deficits associated with mTBIs. Since symptoms often return and persist, it is clear that improved treatment options for these persistent PCSs need to be developed for Veterans with mTBIs.

Rather than a symptom management approach, Defina and colleagues in 2009 describe the possibilities of brain repair in TBI by treatments that would enhance neuroplasticity. Although the concept of neuroplasticity was first presented in the 1940's and further developed in the 1990's, it is only recently that neuroplasticity training and interventions have been developed. According to Defina and colleagues, neuroplasticity interventions may establish a more normalized or stable brain environment and enable the brain to re-organize itself and function more normally. The use of specific neurotransmitters or hormones that are related to the biochemical cascade of TBI, as well as, electromagnetic stimulation, nutraceuticals, median nerve stimulation and neurofeedback have been suggested as possible treatments to effectively normalize the brain environment and maximize natural healing. The benefits of neuro enhancement strategies could potentially reduce suffering and improve quality of life.

Neurofeedback (NFB) is a sub-specialization of biofeedback. Biofeedback is defined as a method of treatment that trains patients to become aware of and learn to control their own physiology to improve physical and psychological health. The NFB system is able to reflect a person's (referred to as the trainee) brain wave pattern instantaneously back to the trainee through conventional electroencephalography (EEG) providing salient information to which the trainee can respond accordingly.

NFB has been demonstrated to influence cortical neuroplasticity significantly and can lead to actual and meaningful microstructural changes in white and gray matter. NFB has been shown to contribute to neuronal rehabilitation by changing connectivities of specific areas of the brain that may have been impaired, and these rehabilitative changes appear to be permanent. Functional (f)MRI studies further validate that NFB may be useful in promoting recovery from neurological disorders that are linked to abnormal patterns of brain connectivity. Hence, this non-invasive and non-pharmacological method may be used to 'normalize' abnormal network activity by manipulating and thereby strengthening region specific brain networks.

In 2019, the PI of this clinical trial conducted a pilot project with the overall objective to ascertain the feasibility of conducting a randomized, controlled trial. In addition to determining its feasibility, this pilot study's objective was to evaluate NFB training as a low risk, non-invasive, effective treatment for Veterans who had an mTBI, while serving in the military. The chronic PCSs targeted were headache, insomnia, and attention difficulties. Perceived quality of life was also assessed pre and post intervention. With the high incidence of PTSD, depression and distress co-occurring with mTBI, these symptoms were also evaluated. It was hypothesized, that those Veterans who receive NFB training will experience a clinically significant benefit. The pilot was expected to show: 1) the study is feasible to conduct at a VA located in the Pacific region; 2) reduction in the frequency and/or severity of headaches; 3) decreased severity of insomnia and/or enhanced perceptions of sleep; 4) improved attention; and 5) improved perceptions of quality of life; and 6) decreased levels of self-reported PTSD, depression, distress and general symptoms. Although 19 Veterans were interested, only four were able to participate in the IRB approved pilot. Since all of the procedures that would be related to a randomized, controlled trial were successfully conducted, the pilot study demonstrated feasibility. All the issues encountered in this pilot study were related to time constraints of the project and the need for funding. The data obtained from the four veterans were very positive. All the hypotheses demonstrated significant clinical gains on the 12 different questionnaires used to assess the outcome of the intervention although the sample size is small.

NFB has been used since the 1960's for symptoms related to mTBI. Duff in his extensive review of the literature, suggests that since the 1960's, studies using NFB, (EEG biofeedback or neurotherapy) have shown that patients can be taught to promote normal functioning in brains with excessively slow wave activity, which is often found in post-concussion syndrome. In a 2013 review of the literature, May and colleagues used a 10-level classification rubric (10 being the highest level e.g. randomized control trials; to the lowest 1 being case study/anecdotal evidence) to classify the research literature of NFB and mTBI. They found two studies at level 5 (randomized waitlist or intention to treat), six studies at level 3 (historical control), ten studies at level 2 (no control group) and five studies at level 1 (case study/anecdotal evidence). Of the 23 studies reviewed, all found NFB to positively impact symptoms associated with mTBI (attention, memory, quality of life, sleep, motor control, coordination, depression, headaches). May and colleagues called for more randomized control group studies and suggested the need for double blind and sham NFB studies. Recent studies have continued to demonstrate support for the use of NFB with symptoms related to mTBI. Nelson and Esty in 2012 found in their small study (n=7) that neurotherapy significantly reduced depression, somatic and memory/attention symptoms, when employed with Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) Veterans diagnosed with TBI and PTSD. A study conducted in 2013 demonstrated that NFB was able to enhance quality of life and perceived control in 29 SMs with mTBI and PTSD. In a control group/waitlist study conducted in 2014, sixty mTBI participants (aged 18-49 years old) received NFB, and it was found that 20 sessions of NFB significantly improved quality of life. Munivenkatappa and colleagues in 2014 provided further validation of the ability of NFB to enhance structural and functional connectivity and cognitive scores of mTBI patients. Arns and Kenemans in 2014 reported in their review of the literature regarding attentional and sleep disorders that NFB is associated with improved sleep quality and sleep onset.

After a thorough meta-analyses of NFB research, Larsen and Sherlin in 2013 rated NFB "probably" efficacious for the treatment of mTBI symptoms, with its limitation being the lack of randomized controlled trials with a large enough sample to obtain power. NFB has been demonstrated as effective in treating symptoms related to mTBI in a sizable number of case reports and research studies. It would appear that the next logical step would be to conduct a randomized control clinical trial evaluating NFB in treating specific persistent PCSs. As post-traumatic headaches, attention problems, and sleep issues were identified as common PCSs, this proposed study will therefore target those Veterans with deployment associated mTBIs and who are experiencing those PCSs of chronic headaches, insomnia and attentional difficulties. Since persistent PCS symptoms have been demonstrated to impact quality of life, this variable will also be evaluated. Quality of life is considered one of the most clinically important variables since it a central part of patients' everyday functioning and experience.

OBJECTIVES: The objective of this randomized control clinical trial is to provide data on the clinical impact of NFB treatment in Operation Enduring Freedom (OEF), Operation Iraqi Freedom (OIF), and/or Operation New Dawn (OND) Veterans diagnosed with mild traumatic brain injury (mTBI) and experiencing persistent post-concussive symptoms as compared to a randomized control group, who will only receive usual care. Comparisons will be made at baseline, at the study treatment midpoint (around 4-6 weeks), and conclusion of study treatment (around 8-10 weeks) and at a two-month follow-up.

The effect of NFB will be assessed on the following:

1. Frequency of headaches as measured by NEUROQOLTBI headache tool, and headache impact on functioning as measured by Headache Impact Tool (HIT-6)

2. Severity of sleep disturbance as measured by Insomnia Severity Index (ISI) and quality of sleep as measured by the NEUROQOLTBI Sleep disturbance tool.

3. Attentional functioning as measured by computerized visual attention performance test (QIKTest) accuracy index

4. Quality of life as measured by Quality of Life after Brain Injury (QOLABI) and NEUROQOLTBI Satisfaction with roles and activities & Ability to Participate in roles and activities.

5. General physical and emotional symptoms possibly co-occurring with mTBI as measured by self-report using General Symptom Scale (GSI), Depression, Anxiety and Stress Scale (DASS21), Post-Traumatic Stress Disorder Checklist (PCL), Patient Health Questionnaire-Depression (PHQ9), and NEUROQOLTB Positive affect and wellbeing short form.

Hypotheses

The investigators hypothesize that the intervention group, receiving NFB training over the course of treatment, relative to the control group, will experience a clinically and statistically significant change in scores that indicates a:

1. decreased severity of headaches on the NEUROQOLTBI headache tool and enhanced functioning on the HIT-6.

2. greater improvement in perceptions of quality of sleep on the NEUROQOLTBI Sleep disturbance tool and decreased severity of sleep disturbance on the ISI.

3. greater improvement in attention function in the QIKTEST accuracy index.

4. greater improvement in quality of life as shown by enhanced involvement in roles on the NEUROQOLTBI Satisfaction with roles and activities & Ability to Participate in roles and activities tools and on the QOLATBI baseline scores.

5. greater improvement in general physical and emotional symptoms score on the PCL-5; on the PHQ9; on the DASS21; on the GSI, and on the NEUROQOLTBI Positive affect and wellbeing tool

RESEARCH DESIGN: The proposed study is a randomized controlled clinical trial using NFB, also known as EEG biofeedback, as the study intervention. The control group members will continue with their usual care and will receive a15-minute phone call from the PI on a weekly basis to briefly discuss one of eight possible health topics that the treatment group would receive as a normal part of their NFB session, with the only difference is the treatment group will receive NFB. For those participants in the control group, when the control group activities are complete, they will receive NBF and become part of the delayed intervention group.

METHODOLOGY: Male and non-pregnant female OEF-OIF-OND Veterans diagnosed with mTBI, ages 18 to 65 with complaints of chronic headaches, insomnia, and attention difficulties will be invited to participate in this study. It is estimated that 72 Veterans need to complete the study for a statistical meaningful effect. Up to 100 veterans may be enrolled to achieve the desired number of participants. All eligible potential participants will be screened for suicide intent and consented and will fill out a contact information form.

NFB will be the study Intervention. The NFB system will read and interpret a person's brain wave pattern which will be instantaneously fed back to the person providing information, to which a person can respond accordingly. The NFB specialist assumes a coaching role with people training on the NFB system to assist in the achievement of a focused relaxed state, which enhances the overall brain functioning. The significance and unique aspect of NFB is the direct impact on physiological dysregulation, which is the basis of this treatment approach.

The Cygnet NFB system to be used during the course of this study is comprised of a desktop computer or laptop with dual monitors fully loaded with operational Cygnet NFB systems with Neuroamp and Alpha-theta feedback capability. Twenty, one-hour, NFB training sessions will be provided to each participant in the intervention group by a trained NFB specialist over an 8-10-week period. Participants in the intervention group will receive up to 5-sessions but usually 3 session a week. Participants in the control group will continue with their usual treatment and receive a 15-minute call for eight weeks from the PI on a health topic. This will help to keep members of the control group engaged in the project and receive the same information that is offered to the intervention group members. The health topics that are generally discussed during NFB sessions include sleep hygiene, basic nutritional concepts, beverage choices, positive thinking, thought reframing, fitness, daily calming activity, and enhancement of focus strategies.

The benefits to the subject could include: For the participants receiving NFB, benefits may include a decrease in the number and severity of headaches, enhanced sleep, and attention ability and an overall perception of enhanced quality of life. In addition, the participant may experience enhanced positive emotions. Indirect benefits include the knowledge that the participant has contributed to the body of knowledge relating to the efficacy of NFB. There may be no direct benefit to volunteers. The risk to volunteers in this study is designed to be minimal. Because this intervention is a personal biofeedback process, whereby the participants are training themselves based on their own physiological parameters, no serious adverse event is anticipated or expected. Anticipated and not serious brief side effects such as anxiety, a tightness in muscles, stomach discomfort, or mental cloudiness may be experienced but are expected to go away within minutes. Most people feel relaxed and calm during and after NFB training.

This project will be an important step towards the broad clinical implementation of an evidence-based treatment solution for Veterans experiencing chronic headaches, insomnia and attention disorders. This study directly maps onto VA initiatives focused on enhancing Veteran's access to evidence based non-invasive and non-pharmacological treatment options. Also, because of the ethno-culturally diverse population in Hawai'i, results can inform VHA providers about the use of NFB among diverse groups of Veterans, including Asian American and Native Hawaiian/Other Pacific Islander Veterans not often adequately represented in other studies. NFB is not widely used in the VA, therefore the results will be highly relevant to VA clinicians, administrators, and policy makers nationwide who seek effective non-invasive treatment options. Results can guide future full clinical trial studies on use of NFB in relation to current best practices for care of Veterans in relation to other issues experienced by Veterans, i.e. PTSD, Pain, etc. Dissemination activities will target a broad audience and will include: (1) a one-sheet summary abstract, (2) web-based fact sheets for several VA venues, (3) manuscripts and publications for both professional and non-professional channels. The publications stemming from this research project will be made available to the public through the National Library of Medicine PubMed Central website within one year after the date of publication. Costs for producing the dissemination materials will be minimal. The investigators will also deliver local and national presentations at VA and academic professional conferences. Finally, long term research results can assist in the future development effective NFB protocols that can be potentially implemented in VA clinical settings and disseminated directly to clinical settings via existing infrastructures established by this research team. ;

Related Conditions & MeSH terms

• Chronic Attention Disorder
• Chronic Headache
• Chronic Insomnia
• Cognition Disorders
• Concussion
• Headache
• Headache Disorders
• mTBI
• Post-Concussion Syndrome
• Post-Concussive Symptoms
• Sleep Initiation and Maintenance Disorders

• NCT number: NCT04195685
• Study type: Interventional
• Source: VA Office of Research and Development
• Contact: Judy M Carlson, EdD
• Phone: (808) 433-6677
• Email: judy.carlson@va.gov
• Status: Recruiting
• Phase: N/A
• Start date: January 18, 2021
• Completion date: March 29, 2025