Chronic Attention Disorder, Chronic Headache, Chronic Insomnia, Concussion, mTBI, Post-Concussive Symptoms
Conditions
Keywords
Neurofeedback, Infra-Low Frequency Neurofeedback, Veterans, Integrative Health Treatment, mTBI, Concussion, Post-concussive Symptoms, Chronic Headaches, Chronic Insomnia, Chronic Attention Disorder, Quality of Life, Emotional Responses, PTSD, Depression
Brief 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). Participants will be randomized into the intervention or control group. Groups will be compared on primary measures of headache, insomnia and attention. Other outcomes of interest include post-traumatic stress symptoms, depression, quality of life and other measures of well-being.
Detailed description
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). Participants will be randomized into the intervention or control group. Groups will be compared on primary measures of headache, insomnia and attention. Other outcomes of interest include post-traumatic stress symptoms, depression, quality of life and other measures of well-being. Both the intervention and control group will participate in four assessment sessions. The assessment sessions will occur at the beginning of the study, at 4-6 weeks, at 8-10 weeks, and 2-months later. Participation in this research will last about 4 months. Those in the control group will be offered neurofeedback treatment, extending their participation time by 4 months (8 months total participation).
Interventions
PROCEDURENeurofeedback (NFB)
Participants are seated in a comfortable chair and have common EEG electrodes with a pre-application of EEG adhesion conductive paste placed on scalp. The participant will receive coaching as they look at the game training screen and focus on the image. The game training screen provides almost instantaneous feedback (within 200 milliseconds) to participants about brain functioning. Twenty, one-hour, NFB training sessions will be provided by a trained NFB specialist over an 8-10-week period with up to 5-sessions but usually 3 sessions a week. The specific NFB special use system that will be used is the Cygnet NFB System from Bee Medic Corporation. The latest technological advances in this system has enabled training frequencies in the infra-low frequency range as well as in all other relevant frequency ranges which is a breakthrough capacity not available on any other NFB system. This will enable the individualized training to the person's brain training preference.
Sponsors
VA Office of Research and Development
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The proposed study is a randomized controlled clinical trial using Neurofeedback (NFB) as the study intervention. The control group members will continue with their usual care and will receive a 15-minute phone call from an Investigator on a weekly basis to briefly discuss one of eight possible health topics (sleep hygiene, basic nutritional concepts, beverage choices, positive thinking, thought reframing, fitness, daily calming activity, and enhancement of focus strategies) that the treatment group would receive as a normal part of their NFB session. At the end of the Control group activities, the participant will enter the delayed intervention group. 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 (up to 5-sessions but usually 3 sessions a week).
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Male and non-pregnant female OEF-OIF-OND Veterans diagnosed with mTBI ages 18 to 65 * Complaints of chronic headaches, insomnia, and attention difficulties * Able to read and write English * Able to comprehend what they read * Able to follow directions
Exclusion criteria
* Pregnant female Veteran * Non OEF-OIF-OND Veteran who is diagnosed with mTBI * Under the age of 18 or over the age of 65 * Severe TBI * Impaired decision-making capacity * Unable to comply with study visit schedule * Suicide Intent as indicated by a positive response to questions 3, 4, 5, or 8 on the Columbia Suicide Severity Rating Scale (C-SSRS) secondary screen
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| NEUROQOLTBI Positive Affect and Well-being-short Form | Change from baseline midtreatment at 4-6 weeks, change from baseline endpoint at 8-10 weeks, and change from baseline at 2 month follow-up | Developed as part of NIH Toolbox NEUROQOL TBI. It is comprised of 10 questions related to level of positive attitude and sense of well-being (9 items, 5 min). Score range: 9-45. Higher score better outcome. |
| QIKtest Continuous Performance Test - Accuracy Index | Change from baseline midtreatment at 4-6 weeks, change from baseline endpoint at 8-10 weeks, and change from baseline at 2 month follow-up | Computerized visual performance test to assess attention and impulse control, speed and consistency of response. Specifically intended for use by neurofeedback clinicians. (21 min). Higher scores indicate better performance. Score range: 165-420. |
| Quality of Life After Brain Injury (QOLIBRI) | Change from baseline midtreatment at 4-6 weeks, change from baseline endpoint at 8-10 weeks, and change from baseline at 2 month follow-up | A 37-item instrument consisting of 6 scales measuring cognition, self, daily life and autonomy, social relationships, emotions, and physical problems. Designed to measure quality of life specific for TBI. (37 items, 15 min). Score range: 0-100. Higher score suggests better outcome. |
| NEUROQOLTBI Satisfaction With Social Roles and Activities Short Form | Change from baseline midtreatment at 4-6 weeks, change from baseline endpoint at 8-10 weeks, and change from baseline at 2 month follow-up | Developed as part of NIH Toolbox NEUROQOL TBI. It is comprised of 10 questions related to level of satisfaction with life roles and activities. (10 items, 5 min). Score range: 8-40. Higher score suggests better outcome. |
| NEUROQOLTBI Ability to Participate in Social Roles and Activities Short Form | Change from baseline midtreatment at 4-6 weeks, change from baseline endpoint at 8-10 weeks, and change from baseline at 2 month follow-up | Developed as part of NIH Toolbox NEUROQOL TBI. It is comprised of 10 questions related to level of ability to do life roles and activities. (10 items, 5 min). Score range 8-40. Higher score suggests better outcome. |
| Headache Impact Test (HIT-6) | Change from baseline midtreatment at 4-6 weeks, change from baseline endpoint at 8-10 weeks, and change from baseline at 2 month follow-up | The HIT-6 is a 6-question tool designed to describe and communicate the way people feel and what they cannot do because of their headache. (6 questions, 3 min) Scores vary from 36 - 78. Higher score worse outcome. |
| NEUROQOLTBI Headache Pain Short Form | Change from baseline midtreatment at 4-6 weeks, change from baseline endpoint at 8-10 weeks, and change from baseline at 2 month follow-up | Developed as part of NIH Toolbox NEUROQOL TBI. It is comprised of 10 questions related to the nature and response to headaches. (10 items, 5 minutes). Score range 10-50. Higher scores suggest worse outcome. |
| Insomnia Severity Index (ISI) | Change from baseline midtreatment at 4-6 weeks, change from baseline endpoint at 8-10 weeks, and change from baseline at 2 month follow-up | Seven question self-report instrument used to quantify perceived current insomnia. Targets past week's symptoms and daytime consequences consistent with DSM-IV criteria. (7 items, 5 min) Scores vary from 0 - 28. Higher score worse outcome. |
| NEUROQOLTBI Sleep Disturbance Short Form | Change from baseline midtreatment at 4-6 weeks, change from baseline endpoint at 8-10 weeks, and change from baseline at 2 month follow-up | Developed as part of NIH Toolbox NEUROQOL TBI. It is comprised of 8 questions related to the sleep experience and impact. (8 items, 5 minutes). Score range: 8-40. Higher scores suggest worse outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Depression, Anxiety and Stress Scale 21 (DASS21) | Change from baseline midtreatment at 4-6 weeks, change from baseline endpoint at 8-10 weeks, and change from baseline at 2 month follow-up | DASS21 is a set of three self-report scales designed to measure the negative emotional states of depression, anxiety and stress. Can be used as a single assessment of psychological distress (21 items, 10 min). Score varies from 0 - 63. Higher score suggests worse outcome. |
| Patient Health Questionnaire-9 (PHQ-9) | Change from baseline midtreatment at 4-6 weeks, change from baseline endpoint at 8-10 weeks, and change from baseline at 2 month follow-up | PHQ-9 is a nine-item depression self-report module from the full Patient Health Questionnaire. Scores range from 0-27. (9 items, 2-5 min) Score varies from 0-27. Higher score suggests worse outcome. |
| General Symptom Inventory (GSI) | Change from baseline midtreatment at 4-6 weeks, change from baseline endpoint at 8-10 weeks, and change from baseline at 2 month follow-up | Self-report instrument of symptoms in 7 categories including sleep, attention and learning, sensory, behavioral, emotional, physical, and pain (less than 10 min). Score varies from 0-464. Higher score suggests worse outcome. |
| Posttraumatic Stress Disorder Checklist (PCL-5) | Change from baseline midtreatment at 4-6 weeks, change from baseline endpoint at 8-10 weeks, and change from baseline at 2 month follow-up | The PCL-5 is a 20-item questionnaire, corresponding to the DSM-5 symptom criteria for PTSD. The wording of PCL-5 items reflects both changes to existing symptoms and the addition of new symptoms in DSM-5. (20 items, 5-10 min) Score varies from 0-80. Higher score suggests worse outcome. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| NFB Intervention The NFB system will read and interpret a participant's brain wave pattern which will be instantaneously fed back to the participant providing information, to which a participant can respond accordingly. The NFB specialist assumes a coaching role with people training on the NFB special use 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. Twenty, one-hour, NFB training sessions will be provided to each participant in the intervention group and Delayed intervention group (those participants who completed the Control Group activities) 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 sessions a week
Neurofeedback (NFB): Participants are seated in a comfortable chair and have common EEG electrodes with a pre-application of EEG adhesion conductive paste placed on scalp. The participant will receive coaching as they look at the game training screen and focus on the image. The game training screen provides almost instantaneous feedback (within 200 milliseconds) to participants about brain functioning. The Cygnet NFB System will be used, which enables training frequencies in the infra-low frequency range. This will enable the individualized training to the person's brain training preference. | 43 |
| Control Group Participants in the control group will continue with their usual treatment and will receive a 15-minute call once a week for eight weeks from an Investigator 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. | 44 |
| Total | 87 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 4 |
| Overall Study | Withdrawal by Subject | 6 | 2 |
Baseline characteristics
| Characteristic | NFB Intervention | Control Group | Total |
|---|---|---|---|
| Age, Continuous | 45.8 years STANDARD_DEVIATION 7.7 | 45.0 years STANDARD_DEVIATION 8.4 | 45.4 years STANDARD_DEVIATION 8.1 |
| Depression, Anxiety and Stress Scale (DASS21) | 24.2 score on a scale STANDARD_DEVIATION 15.3 | 23.9 score on a scale STANDARD_DEVIATION 12.4 | 24.1 score on a scale STANDARD_DEVIATION 13.9 |
| General Symptom Scale (GSI) | 166.6 score on a scale STANDARD_DEVIATION 83.7 | 156.7 score on a scale STANDARD_DEVIATION 54 | 161.7 score on a scale STANDARD_DEVIATION 68.9 |
| Headache Impact Tool (HIT-6) | 61.7 score on a scale STANDARD_DEVIATION 8.8 | 62.8 score on a scale STANDARD_DEVIATION 5.6 | 62.3 score on a scale STANDARD_DEVIATION 7.2 |
| Insomnia Severity Index (ISI) | 19.4 score on a scale STANDARD_DEVIATION 4.6 | 18.5 score on a scale STANDARD_DEVIATION 5.6 | 19.0 score on a scale STANDARD_DEVIATION 5.1 |
| NEUROQOLTBI Ability to participate in social roles and activities | 25.0 score on a scale STANDARD_DEVIATION 6.8 | 24.4 score on a scale STANDARD_DEVIATION 5.7 | 24.7 score on a scale STANDARD_DEVIATION 6.3 |
| NEUROQOLTBI Headache Tool | 32.0 score on a scale STANDARD_DEVIATION 10.9 | 31.7 score on a scale STANDARD_DEVIATION 8.5 | 31.9 score on a scale STANDARD_DEVIATION 9.7 |
| NEUROQOLTBI Positive affect and wellbeing | 29.9 score on a scale STANDARD_DEVIATION 8.2 | 29.8 score on a scale STANDARD_DEVIATION 5.8 | 29.9 score on a scale STANDARD_DEVIATION 7 |
| NEUROQOLTBI Satisfaction with roles and activities | 23.1 score on a scale STANDARD_DEVIATION 7.4 | 21.9 score on a scale STANDARD_DEVIATION 6.1 | 22.5 score on a scale STANDARD_DEVIATION 6.8 |
| NEUROQOLTBI Sleep Disturbance | 25.8 score on a scale STANDARD_DEVIATION 6.7 | 26.0 score on a scale STANDARD_DEVIATION 6 | 25.9 score on a scale STANDARD_DEVIATION 6.4 |
| Patient Health Questionnaire-Depression (PHQ9) | 14.3 score on a scale STANDARD_DEVIATION 6.6 | 14.3 score on a scale STANDARD_DEVIATION 5.7 | 14.3 score on a scale STANDARD_DEVIATION 6.2 |
| Post-Traumatic Stress Disorder Checklist (PCL-5) | 40.7 score on a scale STANDARD_DEVIATION 20.4 | 40.9 score on a scale STANDARD_DEVIATION 18.7 | 40.8 score on a scale STANDARD_DEVIATION 19.6 |
| QIK test accuracy index | 232.9 score on a scale STANDARD_DEVIATION 39 | 241.3 score on a scale STANDARD_DEVIATION 44.9 | 237.1 score on a scale STANDARD_DEVIATION 42 |
| Quality of Life after Brain Injury (QOLIBRI) | 46.3 score on a scale STANDARD_DEVIATION 17.3 | 46.3 score on a scale STANDARD_DEVIATION 17.2 | 46.3 score on a scale STANDARD_DEVIATION 17.3 |
| Race/Ethnicity, Customized Self-identified ethnicity African/Black | 4 Participants | 8 Participants | 12 Participants |
| Race/Ethnicity, Customized Self-identified ethnicity Asian | 4 Participants | 5 Participants | 9 Participants |
| Race/Ethnicity, Customized Self-identified ethnicity European/Caucasian | 12 Participants | 10 Participants | 22 Participants |
| Race/Ethnicity, Customized Self-identified ethnicity Hawaiian/Pacific Islander | 3 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized Self-identified ethnicity Hispanic | 9 Participants | 3 Participants | 12 Participants |
| Race/Ethnicity, Customized Self-identified ethnicity More than one ethnicity | 10 Participants | 15 Participants | 25 Participants |
| Race/Ethnicity, Customized Self-identified ethnicity Native American | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Self-identified ethnicity Refused/Unknown | 0 Participants | 2 Participants | 2 Participants |
| Sex: Female, Male Female | 6 Participants | 8 Participants | 14 Participants |
| Sex: Female, Male Male | 37 Participants | 36 Participants | 73 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 43 | 0 / 44 |
| other Total, other adverse events | 3 / 43 | 12 / 44 |
| serious Total, serious adverse events | 1 / 43 | 1 / 44 |
Outcome results
Primary
Headache Impact Test (HIT-6)
The HIT-6 is a 6-question tool designed to describe and communicate the way people feel and what they cannot do because of their headache. (6 questions, 3 min) Scores vary from 36 - 78. Higher score worse outcome.
Time frame: Change from baseline midtreatment at 4-6 weeks, change from baseline endpoint at 8-10 weeks, and change from baseline at 2 month follow-up
Population: Primary analyses were intention to treat, which included all participants assigned to either group. Missing data were addressed using a multiple imputation approach.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NFB Intervention | Headache Impact Test (HIT-6) | Mid-treatment | 53.2 score on a scale | Standard Deviation 9.8 |
| NFB Intervention | Headache Impact Test (HIT-6) | Post-treatment | 49.2 score on a scale | Standard Deviation 10.4 |
| NFB Intervention | Headache Impact Test (HIT-6) | 2-month follow-up | 52.2 score on a scale | Standard Deviation 11.5 |
| Control Group | Headache Impact Test (HIT-6) | Mid-treatment | 61.4 score on a scale | Standard Deviation 6.6 |
| Control Group | Headache Impact Test (HIT-6) | Post-treatment | 60.9 score on a scale | Standard Deviation 7.4 |
| Control Group | Headache Impact Test (HIT-6) | 2-month follow-up | 62.6 score on a scale | Standard Deviation 8.7 |
Comparison: The primary endpoint was evaluated by assessing the change in severity scores from baseline to the end of treatment, comparing the NFB and control groups. A two-sample t-test was used to test the mean change in severity scores between treatment arms. Statistical tests were two-sided with a 5% significance level (Type I error rate).p-value: <0.000195% CI: [7, 14.4]t-test, 2 sided
Primary
Insomnia Severity Index (ISI)
Seven question self-report instrument used to quantify perceived current insomnia. Targets past week's symptoms and daytime consequences consistent with DSM-IV criteria. (7 items, 5 min) Scores vary from 0 - 28. Higher score worse outcome.
Time frame: Change from baseline midtreatment at 4-6 weeks, change from baseline endpoint at 8-10 weeks, and change from baseline at 2 month follow-up
Population: Primary analyses were intention to treat, which included all participants assigned to either group. Missing data were addressed using a multiple imputation approach
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NFB Intervention | Insomnia Severity Index (ISI) | Mid-treatment | 11.5 score on a scale | Standard Deviation 7.1 |
| NFB Intervention | Insomnia Severity Index (ISI) | Post-treatment | 7.7 score on a scale | Standard Deviation 7.3 |
| NFB Intervention | Insomnia Severity Index (ISI) | 2-month follow-up | 10.2 score on a scale | Standard Deviation 7.9 |
| Control Group | Insomnia Severity Index (ISI) | Mid-treatment | 17.2 score on a scale | Standard Deviation 6.2 |
| Control Group | Insomnia Severity Index (ISI) | Post-treatment | 17.1 score on a scale | Standard Deviation 6.3 |
| Control Group | Insomnia Severity Index (ISI) | 2-month follow-up | 17.0 score on a scale | Standard Deviation 7 |
Comparison: The primary endpoint was evaluated by assessing the change in severity scores from baseline to the end of treatment, comparing the NFB and control groups. A two-sample t-test was used to test the mean change in severity scores between treatment arms. Statistical tests were two-sided with a 5% significance level (Type I error rate).p-value: <0.000195% CI: [7.4, 13.2]t-test, 2 sided
Primary
NEUROQOLTBI Ability to Participate in Social Roles and Activities Short Form
Developed as part of NIH Toolbox NEUROQOL TBI. It is comprised of 10 questions related to level of ability to do life roles and activities. (10 items, 5 min). Score range 8-40. Higher score suggests better outcome.
Time frame: Change from baseline midtreatment at 4-6 weeks, change from baseline endpoint at 8-10 weeks, and change from baseline at 2 month follow-up
Population: Primary analyses were intention to treat, which included all participants assigned to either group. Missing data were addressed using a multiple imputation approach.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NFB Intervention | NEUROQOLTBI Ability to Participate in Social Roles and Activities Short Form | Mid-treatment | 29.1 score on a scale | Standard Deviation 7.3 |
| NFB Intervention | NEUROQOLTBI Ability to Participate in Social Roles and Activities Short Form | Post-treatment | 31.0 score on a scale | Standard Deviation 8.2 |
| NFB Intervention | NEUROQOLTBI Ability to Participate in Social Roles and Activities Short Form | 2-month follow-up | 29.7 score on a scale | Standard Deviation 8.4 |
| Control Group | NEUROQOLTBI Ability to Participate in Social Roles and Activities Short Form | Mid-treatment | 24.7 score on a scale | Standard Deviation 5.8 |
| Control Group | NEUROQOLTBI Ability to Participate in Social Roles and Activities Short Form | Post-treatment | 24.2 score on a scale | Standard Deviation 6.7 |
| Control Group | NEUROQOLTBI Ability to Participate in Social Roles and Activities Short Form | 2-month follow-up | 24.8 score on a scale | Standard Deviation 6.6 |
Comparison: The primary endpoint was evaluated by assessing the change in severity scores from baseline to the end of treatment, comparing the NFB and control groups. A two-sample t-test was used to test the mean change in severity scores between treatment arms. Statistical tests were two-sided with a 5% significance level (Type I error rate).p-value: <0.000195% CI: [-9, -3.4]t-test, 2 sided
Primary
NEUROQOLTBI Headache Pain Short Form
Developed as part of NIH Toolbox NEUROQOL TBI. It is comprised of 10 questions related to the nature and response to headaches. (10 items, 5 minutes). Score range 10-50. Higher scores suggest worse outcome.
Time frame: Change from baseline midtreatment at 4-6 weeks, change from baseline endpoint at 8-10 weeks, and change from baseline at 2 month follow-up
Population: Primary analyses were intention to treat, which included all participants assigned to either group. Missing data were addressed using a multiple imputation approach.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NFB Intervention | NEUROQOLTBI Headache Pain Short Form | Mid-treatment | 21.3 score on a scale | Standard Deviation 11.3 |
| NFB Intervention | NEUROQOLTBI Headache Pain Short Form | Post-treatment | 18.9 score on a scale | Standard Deviation 11.2 |
| NFB Intervention | NEUROQOLTBI Headache Pain Short Form | 2-month follow-up | 23.1 score on a scale | Standard Deviation 13 |
| Control Group | NEUROQOLTBI Headache Pain Short Form | Mid-treatment | 28.5 score on a scale | Standard Deviation 10.2 |
| Control Group | NEUROQOLTBI Headache Pain Short Form | Post-treatment | 28.0 score on a scale | Standard Deviation 11.6 |
| Control Group | NEUROQOLTBI Headache Pain Short Form | 2-month follow-up | 32.4 score on a scale | Standard Deviation 11.3 |
Comparison: The primary endpoint was evaluated by assessing the change in severity scores from baseline to the end of treatment, comparing the NFB and control groups. A two-sample t-test was used to test the mean change in severity scores between treatment arms. Statistical tests were two-sided with a 5% significance level (Type I error rate).p-value: <0.000195% CI: [4.9, 14]t-test, 2 sided
Primary
NEUROQOLTBI Positive Affect and Well-being-short Form
Developed as part of NIH Toolbox NEUROQOL TBI. It is comprised of 10 questions related to level of positive attitude and sense of well-being (9 items, 5 min). Score range: 9-45. Higher score better outcome.
Time frame: Change from baseline midtreatment at 4-6 weeks, change from baseline endpoint at 8-10 weeks, and change from baseline at 2 month follow-up
Population: Primary analyses were intention to treat, which included all participants assigned to either group. Missing data were addressed using a multiple imputation approach.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NFB Intervention | NEUROQOLTBI Positive Affect and Well-being-short Form | Mid-treatment | 33.5 score on a scale | Standard Deviation 7.3 |
| NFB Intervention | NEUROQOLTBI Positive Affect and Well-being-short Form | Post-treatment | 35.5 score on a scale | Standard Deviation 8.2 |
| NFB Intervention | NEUROQOLTBI Positive Affect and Well-being-short Form | 2-month follow-up | 34.7 score on a scale | Standard Deviation 8.5 |
| Control Group | NEUROQOLTBI Positive Affect and Well-being-short Form | Mid-treatment | 30.2 score on a scale | Standard Deviation 6.8 |
| Control Group | NEUROQOLTBI Positive Affect and Well-being-short Form | Post-treatment | 31.0 score on a scale | Standard Deviation 7 |
| Control Group | NEUROQOLTBI Positive Affect and Well-being-short Form | 2-month follow-up | 30.1 score on a scale | Standard Deviation 7.1 |
p-value: 0.003395% CI: [-7.4, -1.5]t-test, 2 sided
Primary
NEUROQOLTBI Satisfaction With Social Roles and Activities Short Form
Developed as part of NIH Toolbox NEUROQOL TBI. It is comprised of 10 questions related to level of satisfaction with life roles and activities. (10 items, 5 min). Score range: 8-40. Higher score suggests better outcome.
Time frame: Change from baseline midtreatment at 4-6 weeks, change from baseline endpoint at 8-10 weeks, and change from baseline at 2 month follow-up
Population: Primary analyses were intention to treat, which included all participants assigned to either group. Missing data were addressed using a multiple imputation approach.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NFB Intervention | NEUROQOLTBI Satisfaction With Social Roles and Activities Short Form | Mid-treatment | 33.5 score on a scale | Standard Deviation 7.6 |
| NFB Intervention | NEUROQOLTBI Satisfaction With Social Roles and Activities Short Form | Post-treatment | 35.4 score on a scale | Standard Deviation 8.7 |
| NFB Intervention | NEUROQOLTBI Satisfaction With Social Roles and Activities Short Form | 2-month follow-up | 34.8 score on a scale | Standard Deviation 8.5 |
| Control Group | NEUROQOLTBI Satisfaction With Social Roles and Activities Short Form | Mid-treatment | 30.0 score on a scale | Standard Deviation 6.8 |
| Control Group | NEUROQOLTBI Satisfaction With Social Roles and Activities Short Form | Post-treatment | 31.2 score on a scale | Standard Deviation 7.6 |
| Control Group | NEUROQOLTBI Satisfaction With Social Roles and Activities Short Form | 2-month follow-up | 30.0 score on a scale | Standard Deviation 7.5 |
Comparison: The primary endpoint was evaluated by assessing the change in severity scores from baseline to the end of treatment, comparing the NFB and control groups. A two-sample t-test was used to test the mean change in severity scores between treatment arms. Statistical tests were two-sided with a 5% significance level (Type I error rate).p-value: 0.000295% CI: [-11.1, -3.4]t-test, 2 sided
Primary
NEUROQOLTBI Sleep Disturbance Short Form
Developed as part of NIH Toolbox NEUROQOL TBI. It is comprised of 8 questions related to the sleep experience and impact. (8 items, 5 minutes). Score range: 8-40. Higher scores suggest worse outcome.
Time frame: Change from baseline midtreatment at 4-6 weeks, change from baseline endpoint at 8-10 weeks, and change from baseline at 2 month follow-up
Population: Primary analyses were intention to treat, which included all participants assigned to either group. Missing data were addressed using a multiple imputation approach
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NFB Intervention | NEUROQOLTBI Sleep Disturbance Short Form | 2-month follow-up | 28.6 score on a scale | Standard Deviation 9.9 |
| NFB Intervention | NEUROQOLTBI Sleep Disturbance Short Form | Mid-treatment | 29.2 score on a scale | Standard Deviation 8.1 |
| NFB Intervention | NEUROQOLTBI Sleep Disturbance Short Form | Post-treatment | 31.2 score on a scale | Standard Deviation 9.9 |
| Control Group | NEUROQOLTBI Sleep Disturbance Short Form | Post-treatment | 22.3 score on a scale | Standard Deviation 8 |
| Control Group | NEUROQOLTBI Sleep Disturbance Short Form | Mid-treatment | 22.0 score on a scale | Standard Deviation 7.3 |
| Control Group | NEUROQOLTBI Sleep Disturbance Short Form | 2-month follow-up | 22.7 score on a scale | Standard Deviation 7.8 |
Comparison: The primary endpoint was evaluated by assessing the change in severity scores from baseline to the end of treatment, comparing the NFB and control groups. A two-sample t-test was used to test the mean change in severity scores between treatment arms. Statistical tests were two-sided with a 5% significance level (Type I error rate).p-value: <0.000195% CI: [4.2, 10.6]t-test, 2 sided
Primary
QIKtest Continuous Performance Test - Accuracy Index
Computerized visual performance test to assess attention and impulse control, speed and consistency of response. Specifically intended for use by neurofeedback clinicians. (21 min). Higher scores indicate better performance. Score range: 165-420.
Time frame: Change from baseline midtreatment at 4-6 weeks, change from baseline endpoint at 8-10 weeks, and change from baseline at 2 month follow-up
Population: Primary analyses were intention to treat, which included all participants assigned to either group. Missing data were addressed using a multiple imputation approach
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NFB Intervention | QIKtest Continuous Performance Test - Accuracy Index | Mid-treatment | 252.0 score on a scale | Standard Deviation 41.9 |
| NFB Intervention | QIKtest Continuous Performance Test - Accuracy Index | Post-treatment | 271.4 score on a scale | Standard Deviation 60.8 |
| NFB Intervention | QIKtest Continuous Performance Test - Accuracy Index | 2-month follow-up | 254.4 score on a scale | Standard Deviation 48.4 |
| Control Group | QIKtest Continuous Performance Test - Accuracy Index | Mid-treatment | 241.6 score on a scale | Standard Deviation 50.1 |
| Control Group | QIKtest Continuous Performance Test - Accuracy Index | Post-treatment | 247.3 score on a scale | Standard Deviation 58.7 |
| Control Group | QIKtest Continuous Performance Test - Accuracy Index | 2-month follow-up | 256.8 score on a scale | Standard Deviation 56.8 |
Comparison: The primary endpoint was evaluated by assessing the change in severity scores from baseline to the end of treatment, comparing the NFB and control groups. A two-sample t-test was used to test the mean change in severity scores between treatment arms. Statistical tests were two-sided with a 5% significance level (Type I error rate).p-value: 0.002295% CI: [-53.3, -11.7]t-test, 2 sided
Primary
Quality of Life After Brain Injury (QOLIBRI)
A 37-item instrument consisting of 6 scales measuring cognition, self, daily life and autonomy, social relationships, emotions, and physical problems. Designed to measure quality of life specific for TBI. (37 items, 15 min). Score range: 0-100. Higher score suggests better outcome.
Time frame: Change from baseline midtreatment at 4-6 weeks, change from baseline endpoint at 8-10 weeks, and change from baseline at 2 month follow-up
Population: Primary analyses were intention to treat, which included all participants assigned to either group. Missing data were addressed using a multiple imputation approach.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NFB Intervention | Quality of Life After Brain Injury (QOLIBRI) | Mid-treatment | 127.4 score on a scale | Standard Deviation 32.6 |
| NFB Intervention | Quality of Life After Brain Injury (QOLIBRI) | Post-treatment | 139.8 score on a scale | Standard Deviation 36.3 |
| NFB Intervention | Quality of Life After Brain Injury (QOLIBRI) | 2-month follow-up | 133.8 score on a scale | Standard Deviation 38.8 |
| Control Group | Quality of Life After Brain Injury (QOLIBRI) | Mid-treatment | 106.8 score on a scale | Standard Deviation 27.4 |
| Control Group | Quality of Life After Brain Injury (QOLIBRI) | Post-treatment | 107.6 score on a scale | Standard Deviation 31 |
| Control Group | Quality of Life After Brain Injury (QOLIBRI) | 2-month follow-up | 108.6 score on a scale | Standard Deviation 30.3 |
Comparison: The primary endpoint was evaluated by assessing the change in severity scores from baseline to the end of treatment, comparing the NFB and control groups. A two-sample t-test was used to test the mean change in severity scores between treatment arms. Statistical tests were two-sided with a 5% significance level (Type I error rate).p-value: <0.000195% CI: [-45, -19.4]t-test, 2 sided
Secondary
Depression, Anxiety and Stress Scale 21 (DASS21)
DASS21 is a set of three self-report scales designed to measure the negative emotional states of depression, anxiety and stress. Can be used as a single assessment of psychological distress (21 items, 10 min). Score varies from 0 - 63. Higher score suggests worse outcome.
Time frame: Change from baseline midtreatment at 4-6 weeks, change from baseline endpoint at 8-10 weeks, and change from baseline at 2 month follow-up
Population: Primary analyses were intention to treat, which included all participants assigned to either group. Missing data were addressed using a multiple imputation approach.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NFB Intervention | Depression, Anxiety and Stress Scale 21 (DASS21) | Mid-treatment | 12.0 score on a scale | Standard Deviation 11.6 |
| NFB Intervention | Depression, Anxiety and Stress Scale 21 (DASS21) | Post-treatment | 10.2 score on a scale | Standard Deviation 12.7 |
| NFB Intervention | Depression, Anxiety and Stress Scale 21 (DASS21) | 2-month follow-up | 13.3 score on a scale | Standard Deviation 13.9 |
| Control Group | Depression, Anxiety and Stress Scale 21 (DASS21) | Mid-treatment | 20.3 score on a scale | Standard Deviation 12.4 |
| Control Group | Depression, Anxiety and Stress Scale 21 (DASS21) | Post-treatment | 19.9 score on a scale | Standard Deviation 13.4 |
| Control Group | Depression, Anxiety and Stress Scale 21 (DASS21) | 2-month follow-up | 23.1 score on a scale | Standard Deviation 13.6 |
Comparison: The primary endpoint was evaluated by assessing the change in severity scores from baseline to the end of treatment, comparing the NFB and control groups. A two-sample t-test was used to test the mean change in severity scores between treatment arms. Statistical tests were two-sided with a 5% significance level (Type I error rate).p-value: 0.000595% CI: [4.4, 15.6]t-test, 2 sided
Secondary
General Symptom Inventory (GSI)
Self-report instrument of symptoms in 7 categories including sleep, attention and learning, sensory, behavioral, emotional, physical, and pain (less than 10 min). Score varies from 0-464. Higher score suggests worse outcome.
Time frame: Change from baseline midtreatment at 4-6 weeks, change from baseline endpoint at 8-10 weeks, and change from baseline at 2 month follow-up
Population: Primary analyses were intention to treat, which included all participants assigned to either group. Missing data were addressed using a multiple imputation approach.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NFB Intervention | General Symptom Inventory (GSI) | Mid-treatment | 108.7 score on a scale | Standard Deviation 75.9 |
| NFB Intervention | General Symptom Inventory (GSI) | Post-treatment | 81.3 score on a scale | Standard Deviation 90.2 |
| NFB Intervention | General Symptom Inventory (GSI) | 2-month follow-up | 103.1 score on a scale | Standard Deviation 97.9 |
| Control Group | General Symptom Inventory (GSI) | Mid-treatment | 151.7 score on a scale | Standard Deviation 61 |
| Control Group | General Symptom Inventory (GSI) | Post-treatment | 139.4 score on a scale | Standard Deviation 73.4 |
| Control Group | General Symptom Inventory (GSI) | 2-month follow-up | 150.4 score on a scale | Standard Deviation 72.9 |
Comparison: The primary endpoint was evaluated by assessing the change in severity scores from baseline to the end of treatment, comparing the NFB and control groups. A two-sample t-test was used to test the mean change in severity scores between treatment arms. Statistical tests were two-sided with a 5% significance level (Type I error rate).p-value: <0.000195% CI: [36.9, 99.2]t-test, 2 sided
Secondary
Patient Health Questionnaire-9 (PHQ-9)
PHQ-9 is a nine-item depression self-report module from the full Patient Health Questionnaire. Scores range from 0-27. (9 items, 2-5 min) Score varies from 0-27. Higher score suggests worse outcome.
Time frame: Change from baseline midtreatment at 4-6 weeks, change from baseline endpoint at 8-10 weeks, and change from baseline at 2 month follow-up
Population: Primary analyses were intention to treat, which included all participants assigned to either group. Missing data were addressed using a multiple imputation approach.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NFB Intervention | Patient Health Questionnaire-9 (PHQ-9) | Mid-treatment | 8.2 score on a scale | Standard Deviation 6.8 |
| NFB Intervention | Patient Health Questionnaire-9 (PHQ-9) | Post-treatment | 5.7 score on a scale | Standard Deviation 7.2 |
| NFB Intervention | Patient Health Questionnaire-9 (PHQ-9) | 2-month follow-up | 7.4 score on a scale | Standard Deviation 7.5 |
| Control Group | Patient Health Questionnaire-9 (PHQ-9) | Mid-treatment | 12.2 score on a scale | Standard Deviation 6.2 |
| Control Group | Patient Health Questionnaire-9 (PHQ-9) | Post-treatment | 12.0 score on a scale | Standard Deviation 6.7 |
| Control Group | Patient Health Questionnaire-9 (PHQ-9) | 2-month follow-up | 13.1 score on a scale | Standard Deviation 7 |
Comparison: The primary endpoint was evaluated by assessing the change in severity scores from baseline to the end of treatment, comparing the NFB and control groups. A two-sample t-test was used to test the mean change in severity scores between treatment arms. Statistical tests were two-sided with a 5% significance level (Type I error rate).p-value: <0.000195% CI: [3.5, 9.2]t-test, 2 sided
Secondary
Posttraumatic Stress Disorder Checklist (PCL-5)
The PCL-5 is a 20-item questionnaire, corresponding to the DSM-5 symptom criteria for PTSD. The wording of PCL-5 items reflects both changes to existing symptoms and the addition of new symptoms in DSM-5. (20 items, 5-10 min) Score varies from 0-80. Higher score suggests worse outcome.
Time frame: Change from baseline midtreatment at 4-6 weeks, change from baseline endpoint at 8-10 weeks, and change from baseline at 2 month follow-up
Population: Primary analyses were intention to treat, which included all participants assigned to either group. Missing data were addressed using a multiple imputation approach.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NFB Intervention | Posttraumatic Stress Disorder Checklist (PCL-5) | Mid-treatment | 25.4 score on a scale | Standard Deviation 19.3 |
| NFB Intervention | Posttraumatic Stress Disorder Checklist (PCL-5) | Post-treatment | 19.3 score on a scale | Standard Deviation 20.2 |
| NFB Intervention | Posttraumatic Stress Disorder Checklist (PCL-5) | 2-follow follow-up | 23.0 score on a scale | Standard Deviation 21 |
| Control Group | Posttraumatic Stress Disorder Checklist (PCL-5) | Mid-treatment | 35.7 score on a scale | Standard Deviation 17.5 |
| Control Group | Posttraumatic Stress Disorder Checklist (PCL-5) | Post-treatment | 33.7 score on a scale | Standard Deviation 19.1 |
| Control Group | Posttraumatic Stress Disorder Checklist (PCL-5) | 2-follow follow-up | 37.1 score on a scale | Standard Deviation 20.3 |
Comparison: The primary endpoint was evaluated by assessing the change in severity scores from baseline to the end of treatment, comparing the NFB and control groups. A two-sample t-test was used to test the mean change in severity scores between treatment arms. Statistical tests were two-sided with a 5% significance level (Type I error rate).p-value: 0.000195% CI: [7.1, 21.4]t-test, 2 sided