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Meditation in Veterans With PTSD and Mild TBI

Neuroimaging Meditation Therapy in Veterans With Co-Morbid TBI and PTSD

Status
Completed
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT02280304
Enrollment
46
Registered
2014-10-31
Start date
2014-11-03
Completion date
2018-03-26
Last updated
2020-03-09

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Concussion, Mild, Stress Disorders, Post-Traumatic

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

BEHAVIORALInner Resources for Veterans (IRV)

Mindfulness and breath-focused mantra therapy which uses techniques that encourage present moment attention for the purpose of improving self-monitoring and self-regulation

BEHAVIORALEssential Skills therapy

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

Palo Alto University
CollaboratorOTHER
VA Office of Research and Development
Lead SponsorFED

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)

Eligibility

Sex/Gender
ALL
Age
18 Years to 49 Years
Healthy volunteers
No

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

MeasureTime frameDescription
Clinician-Administered PTSD Scale (CAPS5)12 weeksChanges in responses in the CAPS5 will be measured in patients following IRV meditation+mantra or ES education control.

Secondary

MeasureTime frameDescription
Number of Participants With Significant Changes in Resting State Functional Connectivity Following Meditation or Control12 weeks and baselineFunctional 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 baselineScores 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

MeasureTime frameDescription
PTSD Checklist 5 (PCL5) Difference Score12 weeks, baselineThe 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 Score12 weeks, baselineThe 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

ArmCount
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
Total37

Withdrawals & dropouts

PeriodReasonFG000FG001
Overall StudyLost to Follow-up78

Baseline characteristics

CharacteristicTotalInner Resources for Veterans Meditation and Mantra TherapyEssential Skills Therapy
Age, Categorical
<=18 years
0 Participants0 Participants0 Participants
Age, Categorical
>=65 years
0 Participants0 Participants0 Participants
Age, Categorical
Between 18 and 65 years
37 Participants19 Participants18 Participants
Age, Continuous36.2 years
STANDARD_DEVIATION 6.2
36.4 years
STANDARD_DEVIATION 7.2
36.1 years
STANDARD_DEVIATION 5.3
PHQ-9 Depression16.5 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 Participants2 Participants5 Participants
Race/Ethnicity, Customized
Ethnicity
Not Hispanic
30 Participants17 Participants13 Participants
Race/Ethnicity, Customized
Race
African American
13 Participants5 Participants8 Participants
Race/Ethnicity, Customized
Race
African American and Other
1 Participants0 Participants1 Participants
Race/Ethnicity, Customized
Race
Caucasian
22 Participants13 Participants9 Participants
Race/Ethnicity, Customized
Race
Other
1 Participants1 Participants0 Participants
Region of Enrollment
United States
37 Participants19 Participants18 Participants
Sex: Female, Male
Female
5 Participants5 Participants0 Participants
Sex: Female, Male
Male
32 Participants14 Participants18 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
0 / 190 / 18
other
Total, other adverse events
0 / 190 / 18
serious
Total, serious adverse events
0 / 190 / 18

Outcome results

Primary

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.

Secondary

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.

ArmMeasureGroupValue (MEAN)Dispersion
Inner Resources for Veterans (IRV) Mindfulness and MantraCommunity Reintegration in Service Members (CRIS)Baseline Extent of Participation34.1 score on a scaleStandard Deviation 5.3
Inner Resources for Veterans (IRV) Mindfulness and MantraCommunity Reintegration in Service Members (CRIS)Baseline Perceived Limitations37.3 score on a scaleStandard Deviation 3.5
Inner Resources for Veterans (IRV) Mindfulness and MantraCommunity Reintegration in Service Members (CRIS)Baseline Satisfaction38.0 score on a scaleStandard Deviation 3.9
Inner Resources for Veterans (IRV) Mindfulness and MantraCommunity Reintegration in Service Members (CRIS)12 weeks Extent of Participation34.9 score on a scaleStandard Deviation 6
Inner Resources for Veterans (IRV) Mindfulness and MantraCommunity Reintegration in Service Members (CRIS)12 weeks Perceived Limitations39.1 score on a scaleStandard Deviation 3.5
Inner Resources for Veterans (IRV) Mindfulness and MantraCommunity Reintegration in Service Members (CRIS)12 weeks Satisfaction38.6 score on a scaleStandard Deviation 5.1
Essential Skills TherapyCommunity Reintegration in Service Members (CRIS)12 weeks Perceived Limitations39.7 score on a scaleStandard Deviation 3.3
Essential Skills TherapyCommunity Reintegration in Service Members (CRIS)Baseline Extent of Participation36.4 score on a scaleStandard Deviation 3.7
Essential Skills TherapyCommunity Reintegration in Service Members (CRIS)12 weeks Extent of Participation38.2 score on a scaleStandard Deviation 6.2
Essential Skills TherapyCommunity Reintegration in Service Members (CRIS)Baseline Perceived Limitations38.9 score on a scaleStandard Deviation 4.6
Essential Skills TherapyCommunity Reintegration in Service Members (CRIS)12 weeks Satisfaction39.7 score on a scaleStandard Deviation 5.3
Essential Skills TherapyCommunity Reintegration in Service Members (CRIS)Baseline Satisfaction38.4 score on a scaleStandard Deviation 3.4
Secondary

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.

ArmMeasureGroupValue (COUNT_OF_PARTICIPANTS)
Inner Resources for Veterans (IRV) Mindfulness and MantraNumber of Participants With Significant Changes in Resting State Functional Connectivity Following Meditation or ControlDMN (MPFC seed) to LPFC0 Participants
Inner Resources for Veterans (IRV) Mindfulness and MantraNumber of Participants With Significant Changes in Resting State Functional Connectivity Following Meditation or ControlDMN (LLP seed) to LPFC0 Participants
Inner Resources for Veterans (IRV) Mindfulness and MantraNumber of Participants With Significant Changes in Resting State Functional Connectivity Following Meditation or ControlAmygdala (right) to ACC0 Participants
Inner Resources for Veterans (IRV) Mindfulness and MantraNumber of Participants With Significant Changes in Resting State Functional Connectivity Following Meditation or ControlDMN (PCC seed) to LPFC0 Participants
Inner Resources for Veterans (IRV) Mindfulness and MantraNumber of Participants With Significant Changes in Resting State Functional Connectivity Following Meditation or ControlAmygdala (left) to ACC0 Participants
Inner Resources for Veterans (IRV) Mindfulness and MantraNumber of Participants With Significant Changes in Resting State Functional Connectivity Following Meditation or ControlDMN (RLP seed) to LPFC0 Participants
Essential Skills TherapyNumber of Participants With Significant Changes in Resting State Functional Connectivity Following Meditation or ControlAmygdala (left) to ACC0 Participants
Essential Skills TherapyNumber of Participants With Significant Changes in Resting State Functional Connectivity Following Meditation or ControlDMN (LLP seed) to LPFC0 Participants
Essential Skills TherapyNumber of Participants With Significant Changes in Resting State Functional Connectivity Following Meditation or ControlDMN (PCC seed) to LPFC0 Participants
Essential Skills TherapyNumber of Participants With Significant Changes in Resting State Functional Connectivity Following Meditation or ControlDMN (RLP seed) to LPFC0 Participants
Essential Skills TherapyNumber of Participants With Significant Changes in Resting State Functional Connectivity Following Meditation or ControlAmygdala (right) to ACC0 Participants
Essential Skills TherapyNumber of Participants With Significant Changes in Resting State Functional Connectivity Following Meditation or ControlDMN (MPFC seed) to LPFC0 Participants
Comparison: Z-scores represent Fisher transformed correlation coefficients representing the correlations between hypothesized regions. Positive values represents positive connectivity between regions. Negative values represent anticorrelations, or negative relations, between hypothesized regions.p-value: >0.05t-test, 1 sided
Other Pre-specified

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.

ArmMeasureValue (MEAN)
Inner Resources for Veterans (IRV) Mindfulness and MantraPatient Health Questionnaire-9 (PHQ-9) Patient Depression Questionnaire Difference Score5.0 Score on a scale
Essential Skills TherapyPatient Health Questionnaire-9 (PHQ-9) Patient Depression Questionnaire Difference Score2.0 Score on a scale
Comparison: Cohen's d effect sizes are reported for changes over time (0 weeks vs. 12 weeks) in each group separately.
Comparison: Cohen's d effect sizes are reported for changes over time (0 weeks vs. 12 weeks) in each group separately.
Other Pre-specified

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.

ArmMeasureValue (MEAN)
Inner Resources for Veterans (IRV) Mindfulness and MantraPTSD Checklist 5 (PCL5) Difference Score11.77 Score on a scale
Essential Skills TherapyPTSD Checklist 5 (PCL5) Difference Score5.58 Score on a scale
Comparison: Cohen's d effect sizes are reported for changes over time (0 weeks vs. 12 weeks) in each group separately.
Comparison: Cohen's d effect sizes are reported for changes over time (0 weeks vs. 12 weeks) in each group separately.
Post Hoc

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.

ArmMeasureValue (NUMBER)
Inner Resources for Veterans (IRV) Mindfulness and MantraRelating 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
Comparison: The extent of community participation prior to therapy was correlated with the functional connectivity of the right hippocampus seed after therapy (post-pre).p-value: <0.000038Regression, Linear
Comparison: The extent of community participation prior to therapy was correlated with the functional connectivity of the right hippocampus seed after therapy (post-pre).p-value: <0.000149Regression, Linear
Post Hoc

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.

ArmMeasureValue (MEAN)Dispersion
Inner Resources for Veterans (IRV) Mindfulness and MantraTest of Additional Limbic Seeds (Hippocampal and Parahippocampal Gyri)0.17 z-scoresStandard Deviation 0.07
Essential Skills TherapyTest of Additional Limbic Seeds (Hippocampal and Parahippocampal Gyri)0.15 z-scoresStandard Deviation 0.03
p-value: <0.0099t-test, 2 sided
p-value: <0.02t-test, 2 sided

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026