Concussion, Mild, Stress Disorders, Post-Traumatic
Conditions
Keywords
Stress Disorders, Post-Traumatic, Concussion, Mild, Brain Injuries, Community Integration, Meditation, Magnetic Resonance Imaging
Brief summary
The goal of this study is to learn more about how Inner Resources for Veterans (IRV), a mindfulness and mantra therapy, helps Veterans with Post Traumatic Stress Disorder (PTSD) and mild traumatic brain injury (mTBI). PTSD is a disorder that occurs after exposure to one or more emotionally traumatic experiences. People with PTSD may experience anxiety, pay extra attention to their surroundings, involuntarily remember their traumatic experiences, and/or want to avoid situations where these symptoms are increased. MTBI may result from being in a blast explosion, with pressure from the blast potentially disrupting the brain's structure and function. At this time, it is not well known how PTSD and mTBI may affect each other. In this study, the investigators will be looking at the behavioral and neurological changes (changes in the brain) and the reductions in PTSD symptoms that may come from participating in this treatment. The investigators are interested in determining if treatment does reverse changes in the brain caused by PTSD and mTBI. To help the investigators understand changes in how the brain functions, the participants will complete a functional magnetic resonance imaging (fMRI) scan before and after either IRV or an active control group. Both conditions are 9-session, 12-week interventions. Participation will help the investigators understand how therapy for PTSD and mTBI impacts the brain's response to emotions and therapeutic processes.
Detailed description
Approximately 18-22% of Operation Enduring Freedom/Operation Iraqi Freedom/ Operation New Dawn (OEF/OIF/OND) Veterans have been diagnosed with posttraumatic stress disorder (PTSD), and 15-30% of Veterans report mild traumatic brain injury (mTBI). The effects of mTBI and PTSD have been evident since military personnel first came home and continue to be difficult to eradicate. At 3-4 months post-deployment, OIF Veterans with mild TBI were more likely to endorse PTSD symptoms than those without mTBI. The co-morbidity may be long-lasting, or at least recurrent, as TBI-related symptoms were strongly associated with traumatic stress five years after injury. In an examination of factors associated with postconcussive symptoms, PTSD was a strong factor. In active duty marines, mTBI during deployment predicted PTSD after deployment, and in a study of OEF-OIF-OND Veterans, 57.3% of those with mTBI had PTSD. The literature on how mTBI and co-morbid PTSD affect each other and the effects on Veterans several years post-deployment is sparse. Treatment recommendations specific to Veterans with both mTBI and PTSD are in flux, and while treatments address each disorder independently, they may not be effective when the two disorders co-occur. Further impacting successful treatment of Veterans is the fact that many Veterans do not seek treatment, in part due to the distance they travel to obtain VA services and stigma. Treatments that are accessible and improve symptoms in patients with mTBI and PTSD alone may facilitate rehabilitation in Veterans with co-morbid mTBI and PTSD. Mindfulness and mantra have been suggested to be effective in Veterans with PTSD and in civilians with TBI, improving quality of life. The current study proposes a type of mindfulness targeted for Veterans, Inner Resources for Veterans (IRV). Inner Resources for Veterans (IRV), a mindfulness and mantra intervention, is based on Inner Resources for Stress, an intervention which utilizes mindfulness, techniques that encourage present moment attention for the purpose of promoting better self-monitoring and self-regulation, and mantra, the repetition of sounds that do not have meaning in order to maintain present focused attention. The Inner Resources protocol targets PTSD and has been associated with reduced PTSD and anxiety symptoms, reduced number of depressive symptoms, and depression remissions at a 9-month follow-up, as well as increased perceived self-efficacy. Pilot results of older combat Veterans with PTSD indicated that Inner Resources is a safe, feasible, and acceptable intervention. The control condition is an active treatment called Essential Skills, a manualized therapy adapted from a similar therapy utilized at multiple VAs as a psychoeducational and symptom management treatment for PTSD. In a previous study at the Michael E. DeBakey VA that did not investigate the effect of mTBI, Essential Skills provided education on the symptoms and effects of PTSD. For example, subjects learned to recognize the circumstances that triggered their symptoms, how to identify and participate in healthy activities, and how to monitor their sleep. In the current study, in Essential Skills, Veterans learn about symptoms of both mTBI and PTSD and coping skills. In addition to the changes in functional and psychological symptoms and neural pathways, IRV would offer Veterans a treatment they could utilize whenever challenging situations occur regardless of location. Since the treatment would be relatively cost-free after initial training, IRV could also dramatically reduce financial burden to both Veterans and VA. Few treatment studies focusing on Veterans with co-morbid mTBI and PTSD support the innovation of this study, as does generation of community integration data to relate to changes in functional connectivity.
Interventions
Mindfulness and breath-focused mantra therapy which uses techniques that encourage present moment attention for the purpose of improving self-monitoring and self-regulation
This active comparator is adapted from a therapy utilized at multiple VAs as a psychoeducational AND symptom management treatment for PTSD. In it, participants learn about mTBI and PTSD symptoms and coping information for PTSD.
Sponsors
Study design
Eligibility
Inclusion criteria
* Mild traumatic brain injury (mTBI) as defined by the VA/DoD Clinical Practice Guideline. * PTSD as assessed by the Clinician Administered PTSD Scale (CAPS); * Aged 18 - 49; * Have not previously participated in meditation training.
Exclusion criteria
The investigators will exclude subjects who: * Meet DSM-IV criteria for drug or alcohol abuse in past 30 days; * Have a history of severe TBI based on any of following: * Glasgow Coma Score \< 8; * alteration of consciousness greater than 24 hours; loss of consciousness greater than 30 minutes; * Have current neurological or general medical conditions known to impact cognitive and/or emotional functioning, including but not limited to: * epilepsy, * Parkinson's disease, * Huntington's disease, * Alzheimer's disease, * stroke, * chemotherapy for cancer; * Have acute psychological instability as assessed by MEDVAMC clinician or study staff or concurrent diagnosis or schizophrenia, schizoaffective disorder, delusional disorder, organic psychosis, and subjects taking antipsychotic medication, and * Have already completed a course of meditation training. * The investigators will also exclude participants with general contraindications for MRI, including metal in or around the head (e.g., orthodontia, non-removable body piercings, etc.), ferromagnetic material in the body (e.g., non-removable body piercings), or non-MRI compatible medical devices.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinician-Administered PTSD Scale (CAPS5) | 12 weeks | Changes in responses in the CAPS5 will be measured in patients following IRV meditation+mantra or ES education control. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Significant Changes in Resting State Functional Connectivity Following Meditation or Control | 12 weeks and baseline | Functional connectivity was measured between the Default Mode Network (DMN) and lateral prefrontal cortex (LPFC), and between the amygdala and anterior cingulate. There were four seeds for the DMN (MPFC, PCC, left lateral parietal, right lateral parietal), and two seeds for the amygdala (right and left). Correlation coefficients representing the degree of connectivity between hypothesized regions were Fisher transformed. An a priori threshold of p\<.001 at the voxel level and p\<.05, FDR corrected for multiple comparisons across the whole brain, at the cluster level were used to determine significant connectivity. |
| Community Reintegration in Service Members (CRIS) | 12 weeks and baseline | Scores at baseline and 12 weeks in responses to the computerized version of the Community Reintegration in Service Members (CRIS-CAT) questionnaire in patients following meditation or control. There are three subscales: Extent of Participation (range 24-90), Perceived Limitations (range 33-99), and Satisfaction (range 34-91). Higher is better. |
Other
| Measure | Time frame | Description |
|---|---|---|
| PTSD Checklist 5 (PCL5) Difference Score | 12 weeks, baseline | The PTSD Checklist 5 (PCL5) is a measure of PTSD symptoms based on DSM-V. The scores fall in the range 0-80; higher scores indicate worse outcome. We calculated the PTSD Checklist 5 (PCL5) difference score by subtracting the value at baseline minus the value at week 12. In this case higher scores represent a reduction in PTSD symptoms. |
| Patient Health Questionnaire-9 (PHQ-9) Patient Depression Questionnaire Difference Score | 12 weeks, baseline | The Patient Health Questionnaire-9 (PHQ-9) measure is a self-report measure of depression symptoms. Scores fall in the range 0-27; higher scores indicate worse outcome. This difference score denotes improvement in symptoms of depression. It was calculated by subtracting the value of PHQ-9 scores at baseline minus PHQ-9 scores scores at week 12. |
Countries
United States
Participant flow
Recruitment details
A total of 364 Veterans were pre-screened. Flyers were posted at the VA and at the University of Houston; however, most of the people who responded had been contacted in Mental Health and Neurology clinics.
Pre-assignment details
Of 364 Veterans pre-screened, 85 were invited to come in for further eligibility assessment for PTSD, mTBI, and exclusionary disorders. Of these, 33 did not attend or excluded themselves, leaving 46 enrolled. Of these, 9 dropped out before group assignment, and 15 dropped out post group assignment, leaving a total of 22 finishing the study.
Participants by arm
| Arm | Count |
|---|---|
| Inner Resources for Veterans Meditation and Mantra Therapy Participants complete meditation and mantra therapy
Inner Resources for Veterans (IRV): Meditation therapy which utilizes mindfulness, techniques that encourage non-judgmental attention to oneself in the present moment | 19 |
| Essential Skills Therapy Participants learn about symptoms of PTSD and mTBI and coping skills for PTSD. | 18 |
| Total | 37 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 7 | 8 |
Baseline characteristics
| Characteristic | Total | Inner Resources for Veterans Meditation and Mantra Therapy | Essential Skills Therapy |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 37 Participants | 19 Participants | 18 Participants |
| Age, Continuous | 36.2 years STANDARD_DEVIATION 6.2 | 36.4 years STANDARD_DEVIATION 7.2 | 36.1 years STANDARD_DEVIATION 5.3 |
| PHQ-9 Depression | 16.5 units on a scale STANDARD_DEVIATION 5.6 | 15.8 units on a scale STANDARD_DEVIATION 5.1 | 17.4 units on a scale STANDARD_DEVIATION 6.4 |
| PTSD Checklist (PCL5) | 49.8 units on a scale STANDARD_DEVIATION 12 | 47.9 units on a scale STANDARD_DEVIATION 11.7 | 52.6 units on a scale STANDARD_DEVIATION 12.3 |
| Race/Ethnicity, Customized Ethnicity Hispanic | 7 Participants | 2 Participants | 5 Participants |
| Race/Ethnicity, Customized Ethnicity Not Hispanic | 30 Participants | 17 Participants | 13 Participants |
| Race/Ethnicity, Customized Race African American | 13 Participants | 5 Participants | 8 Participants |
| Race/Ethnicity, Customized Race African American and Other | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Caucasian | 22 Participants | 13 Participants | 9 Participants |
| Race/Ethnicity, Customized Race Other | 1 Participants | 1 Participants | 0 Participants |
| Region of Enrollment United States | 37 Participants | 19 Participants | 18 Participants |
| Sex: Female, Male Female | 5 Participants | 5 Participants | 0 Participants |
| Sex: Female, Male Male | 32 Participants | 14 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 19 | 0 / 18 |
| other Total, other adverse events | 0 / 19 | 0 / 18 |
| serious Total, serious adverse events | 0 / 19 | 0 / 18 |
Outcome results
Clinician-Administered PTSD Scale (CAPS5)
Changes in responses in the CAPS5 will be measured in patients following IRV meditation+mantra or ES education control.
Time frame: 12 weeks
Population: One CAPS rater did not meet study criteria for expert CAPS administration; as a result, the CAPS data are not considered valid.
Community Reintegration in Service Members (CRIS)
Scores at baseline and 12 weeks in responses to the computerized version of the Community Reintegration in Service Members (CRIS-CAT) questionnaire in patients following meditation or control. There are three subscales: Extent of Participation (range 24-90), Perceived Limitations (range 33-99), and Satisfaction (range 34-91). Higher is better.
Time frame: 12 weeks and baseline
Population: The sample sizes here differ from those reported for other measures because these are the numbers of subjects who had completed the CRIS at both time periods.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Inner Resources for Veterans (IRV) Mindfulness and Mantra | Community Reintegration in Service Members (CRIS) | Baseline Extent of Participation | 34.1 score on a scale | Standard Deviation 5.3 |
| Inner Resources for Veterans (IRV) Mindfulness and Mantra | Community Reintegration in Service Members (CRIS) | Baseline Perceived Limitations | 37.3 score on a scale | Standard Deviation 3.5 |
| Inner Resources for Veterans (IRV) Mindfulness and Mantra | Community Reintegration in Service Members (CRIS) | Baseline Satisfaction | 38.0 score on a scale | Standard Deviation 3.9 |
| Inner Resources for Veterans (IRV) Mindfulness and Mantra | Community Reintegration in Service Members (CRIS) | 12 weeks Extent of Participation | 34.9 score on a scale | Standard Deviation 6 |
| Inner Resources for Veterans (IRV) Mindfulness and Mantra | Community Reintegration in Service Members (CRIS) | 12 weeks Perceived Limitations | 39.1 score on a scale | Standard Deviation 3.5 |
| Inner Resources for Veterans (IRV) Mindfulness and Mantra | Community Reintegration in Service Members (CRIS) | 12 weeks Satisfaction | 38.6 score on a scale | Standard Deviation 5.1 |
| Essential Skills Therapy | Community Reintegration in Service Members (CRIS) | 12 weeks Perceived Limitations | 39.7 score on a scale | Standard Deviation 3.3 |
| Essential Skills Therapy | Community Reintegration in Service Members (CRIS) | Baseline Extent of Participation | 36.4 score on a scale | Standard Deviation 3.7 |
| Essential Skills Therapy | Community Reintegration in Service Members (CRIS) | 12 weeks Extent of Participation | 38.2 score on a scale | Standard Deviation 6.2 |
| Essential Skills Therapy | Community Reintegration in Service Members (CRIS) | Baseline Perceived Limitations | 38.9 score on a scale | Standard Deviation 4.6 |
| Essential Skills Therapy | Community Reintegration in Service Members (CRIS) | 12 weeks Satisfaction | 39.7 score on a scale | Standard Deviation 5.3 |
| Essential Skills Therapy | Community Reintegration in Service Members (CRIS) | Baseline Satisfaction | 38.4 score on a scale | Standard Deviation 3.4 |
Number of Participants With Significant Changes in Resting State Functional Connectivity Following Meditation or Control
Functional connectivity was measured between the Default Mode Network (DMN) and lateral prefrontal cortex (LPFC), and between the amygdala and anterior cingulate. There were four seeds for the DMN (MPFC, PCC, left lateral parietal, right lateral parietal), and two seeds for the amygdala (right and left). Correlation coefficients representing the degree of connectivity between hypothesized regions were Fisher transformed. An a priori threshold of p\<.001 at the voxel level and p\<.05, FDR corrected for multiple comparisons across the whole brain, at the cluster level were used to determine significant connectivity.
Time frame: 12 weeks and baseline
Population: The sample sizes here differ from those reported for other measures because these are the numbers of subjects who had MRI available and with acceptable quality assessment (i.e., not excluded because of excessive motion or sleepiness) for both time periods.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Inner Resources for Veterans (IRV) Mindfulness and Mantra | Number of Participants With Significant Changes in Resting State Functional Connectivity Following Meditation or Control | DMN (MPFC seed) to LPFC | 0 Participants |
| Inner Resources for Veterans (IRV) Mindfulness and Mantra | Number of Participants With Significant Changes in Resting State Functional Connectivity Following Meditation or Control | DMN (LLP seed) to LPFC | 0 Participants |
| Inner Resources for Veterans (IRV) Mindfulness and Mantra | Number of Participants With Significant Changes in Resting State Functional Connectivity Following Meditation or Control | Amygdala (right) to ACC | 0 Participants |
| Inner Resources for Veterans (IRV) Mindfulness and Mantra | Number of Participants With Significant Changes in Resting State Functional Connectivity Following Meditation or Control | DMN (PCC seed) to LPFC | 0 Participants |
| Inner Resources for Veterans (IRV) Mindfulness and Mantra | Number of Participants With Significant Changes in Resting State Functional Connectivity Following Meditation or Control | Amygdala (left) to ACC | 0 Participants |
| Inner Resources for Veterans (IRV) Mindfulness and Mantra | Number of Participants With Significant Changes in Resting State Functional Connectivity Following Meditation or Control | DMN (RLP seed) to LPFC | 0 Participants |
| Essential Skills Therapy | Number of Participants With Significant Changes in Resting State Functional Connectivity Following Meditation or Control | Amygdala (left) to ACC | 0 Participants |
| Essential Skills Therapy | Number of Participants With Significant Changes in Resting State Functional Connectivity Following Meditation or Control | DMN (LLP seed) to LPFC | 0 Participants |
| Essential Skills Therapy | Number of Participants With Significant Changes in Resting State Functional Connectivity Following Meditation or Control | DMN (PCC seed) to LPFC | 0 Participants |
| Essential Skills Therapy | Number of Participants With Significant Changes in Resting State Functional Connectivity Following Meditation or Control | DMN (RLP seed) to LPFC | 0 Participants |
| Essential Skills Therapy | Number of Participants With Significant Changes in Resting State Functional Connectivity Following Meditation or Control | Amygdala (right) to ACC | 0 Participants |
| Essential Skills Therapy | Number of Participants With Significant Changes in Resting State Functional Connectivity Following Meditation or Control | DMN (MPFC seed) to LPFC | 0 Participants |
Patient Health Questionnaire-9 (PHQ-9) Patient Depression Questionnaire Difference Score
The Patient Health Questionnaire-9 (PHQ-9) measure is a self-report measure of depression symptoms. Scores fall in the range 0-27; higher scores indicate worse outcome. This difference score denotes improvement in symptoms of depression. It was calculated by subtracting the value of PHQ-9 scores at baseline minus PHQ-9 scores scores at week 12.
Time frame: 12 weeks, baseline
Population: The sample sizes here differ from those reported for other measures because these are the numbers of subjects who had PHQ-9 forms completed at both time periods.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Inner Resources for Veterans (IRV) Mindfulness and Mantra | Patient Health Questionnaire-9 (PHQ-9) Patient Depression Questionnaire Difference Score | 5.0 Score on a scale |
| Essential Skills Therapy | Patient Health Questionnaire-9 (PHQ-9) Patient Depression Questionnaire Difference Score | 2.0 Score on a scale |
PTSD Checklist 5 (PCL5) Difference Score
The PTSD Checklist 5 (PCL5) is a measure of PTSD symptoms based on DSM-V. The scores fall in the range 0-80; higher scores indicate worse outcome. We calculated the PTSD Checklist 5 (PCL5) difference score by subtracting the value at baseline minus the value at week 12. In this case higher scores represent a reduction in PTSD symptoms.
Time frame: 12 weeks, baseline
Population: The sample sizes here differ from those reported for other measures because these are the numbers of subjects who had completed PCL-5 at both time periods.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Inner Resources for Veterans (IRV) Mindfulness and Mantra | PTSD Checklist 5 (PCL5) Difference Score | 11.77 Score on a scale |
| Essential Skills Therapy | PTSD Checklist 5 (PCL5) Difference Score | 5.58 Score on a scale |
Relating Extent of Participation in the Community (as Measured by the CRIS-CAT) Prior to Therapy to the Functional Connectivity of the Right Hippocampus After Therapy.
The goal was to see if extent of participation in the community prior to therapy could predict the degree of functional connectivity between regions whose connectivity has been suggested to be part of a context processing network, disrupted during PTSD. The hippocampus was investigated because it is one of these regions. (The MPFC and thalamus are others.)
Time frame: 12 weeks
Population: Groups were combined to increase range of the sample size and to examine the general effect of therapy. Subjects (n=16; 9 IRV and 7 ES) were those who had both a post-therapy scan (regardless of therapy, IRV or ES) and CRIS-CAT scores prior to therapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Inner Resources for Veterans (IRV) Mindfulness and Mantra | Relating Extent of Participation in the Community (as Measured by the CRIS-CAT) Prior to Therapy to the Functional Connectivity of the Right Hippocampus After Therapy. | 0.02 beta |
Test of Additional Limbic Seeds (Hippocampal and Parahippocampal Gyri)
Within-group Post vs. Pre t-tests were done for each group with left and right hippocampal and parahippocampal gyrus (PHG) as seeds. Below are mean Fisher-transformed z scores and respective standard deviations of the Pearson's product correlation coefficients between the seed and cluster for each group. Positive mean z-scores scores reflect positive correlations between the seed and the cluster, and negative mean z-scores reflect negative correlations between the seed and the cluster. L IPL = left intraparietal lobule; VMPFC=ventromedial prefrontal cortex
Time frame: 12 weeks
Population: The sample sizes here differ from those reported for other measures because these are the numbers of subjects who had MRI available and with acceptable quality assessment (i.e., not excluded because of excessive motion or sleepiness) for both time periods. Note that the sample sizes are identical to those reported in the secondary outcome section.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Inner Resources for Veterans (IRV) Mindfulness and Mantra | Test of Additional Limbic Seeds (Hippocampal and Parahippocampal Gyri) | 0.17 z-scores | Standard Deviation 0.07 |
| Essential Skills Therapy | Test of Additional Limbic Seeds (Hippocampal and Parahippocampal Gyri) | 0.15 z-scores | Standard Deviation 0.03 |