A Multisite Randomized Controlled Trial of Mindfulness Meditation Therapy for PTSD

Study Overview
=================
Brief Summary
-----------------
Currently, veterans with posttraumatic stress disorder (PTSD) are typically treated with antidepressants which have limited efficacy and yield extremely low remission rates. New and improved treatments are sorely needed, especially in light of the inadequate evidence to support the efficacy of most pharmacologic and most psychotherapy treatments for PTSD. Complementary and Alternative Medicine practices, such as meditation, may fill this void. Several other illnesses often found in association with PTSD, such as chronic pain, anxiety, and depression, have shown positive response to meditation, specifically Mindfulness Based Stress Reduction (MBSR). MBSR is manualized program involving 8 weekly classes and a single 6-hour silent retreat session based on a systematic procedure to develop enhanced non-reactive awareness of the moment-to-moment experience of perceptible mental processes. MBSR is well tolerated, already well disseminated. MBSR has been shown to be effective in reducing conditions that are commonly associated with PTSD, including pain, depression, anxiety and panic, and insomnia. The investigators are conducting a multisite study of Mindfulness Based Stress Reduction (MBSR) compared to Present Centered Group Therapy (PCGT) for the treatment of PTSD. The primary aim of this study will be to determine how well the MBSR form of meditation, i.e. MBSR, works to treat symptoms of PTSD in veterans compared to PCGT. The investigators will evaluate the effects of treatment on levels of mindfulness, depression, PTSD symptom clusters, and response rates. The investigators will evaluate veterans' satisfaction and acceptability of the MBSR intervention. Additionally, biomarkers will be utilized to aid in our understanding of the pathophysiology of meditation and explore the relationship between treatment outcome and neuroimmune response.

Detailed Description
-----------------
This study is a prospective, randomized (1:1), controlled multisite study of MBSR in 180 veterans with PTSD. The investigators will compare the clinical outcomes of MBSR to a credible group therapy control condition called Present Centered Group Therapy (PCGT). The investigators will to evaluate the efficacy of MBSR in the treatment of PTSD, as defined by the Clinician Administered PTSD Scale (CAPS), a gold standard measure that is clinically relevant to PTSD. The CAPS will be rated by a trained assessor who is blind to the whether or not the participant receives the MBSR or PCGT intervention. Secondarily, the investigators will evaluate the effects of MBSR on mindfulness, depression, PTSD symptom clusters, rates of response and evaluate the safety and tolerability of MBRS. The investigators will also explore the subjects' acceptance of and satisfaction with MBSR, whether or not the subjects' treatment preference influences outcome; the stress-immunological-biomarkers as they relate to treatment outcome; and the durability of therapeutic effects of MBSR in the treatment of PTSD. Study Design Overview: Male and female subjects from Active Duty, Reserves, National Guard and/or Veterans with a diagnosis of PTSD will be prospectively randomized 1:1 to receive either MBSR Group therapy or Present Centered Therapy (PCGT) Group (control) for 8 weeks. A cluster of at least 12 participants will be randomized individually to either MBRS or PCGT group therapies, which results in at least 6 participants in each intervention group. A total of 30 groups (15 MBSR Groups and 15 PCGT Groups) are anticipated across three clinical research sites involving at least three different MBSR and three different PCGT instructors/therapists. Outcome assessments (single-blind CAPS and self-report measures) will be obtained at baseline, week 3, week 6, and week 9 (primary endpoint). These assessments will be repeated post-acute treatment at week 16 as an exploratory measure of short-term durability effects.

Official Title
-----------------
A Multisite Randomized Controlled Trial of Mindfulness Meditation Therapy for PTSD

Conditions
-----------------
Posttraumatic Stress Disorder

Intervention / Treatment
-----------------
* Behavioral: Mindfulness Based Stress Reduction
* Behavioral: Present Centered Group Therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Signed and dated informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization form. > or = 18 years of age. Diagnosis of PTSD (DSM-IV-TR criteria; confirmed by MINI and CAPS). Total CAPS score > 45 for the week prior to randomization. No substance use disorders (except for nicotine, caffeine) for 2 weeks prior to randomization (Able to Travel to the clinical sites in Tuscaloosa, AL, Atlanta, GA, or Charleston, SC Exclusion Criteria: Lifetime history of bipolar I, schizophrenia, schizoaffective or cognitive disorders (MINI) Actively considering plans of suicide or homicide (assessed by clinical interview) Psychotic symptoms that in the investigator's opinion impair the subject's ability to give informed consent and participate in the study interventions Severe cognitive disorder (Dementia, severe Traumatic Brain Injury) Clinically significant unstable or severe medical condition that would contraindicate study participation or expose them to an undue risk of a significant adverse event. In regard to vulnerable patient populations, persons with dementia, minors (<age 19), the elderly (>age 65), prisoners and the terminally ill are excluded. Individuals with significant psychotic or dissociative symptoms or severe personality disorder.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mindfulness Based Stress Reduction<br>Mindfulness Based Stress Reduction (MBSR) is a manualized program involving 8 weekly classes and a single 6-hour silent retreat session based on a systematic procedure to develop enhanced non-reactive awareness of the moment-to-moment experience of perceptible mental processes. | Behavioral: Mindfulness Based Stress Reduction<br>* MBSR is a manualized program involving 8 weekly classes and a single 6-hour silent retreat session based on a systematic procedure to develop enhanced non-reactive awareness of the moment-to-moment experience of perceptible mental processes.<br>* Other names: MBSR;|
| Sham Comparator: Present Centered Group Therapy<br>Present Centered Group Therapy (PCGT) serves as a credible control for the nonspecific effects of a group-based intervention (i.e. controls for time, attention, expectation of recovery, and recognition of the illness). | Behavioral: Present Centered Group Therapy<br>* The comparison control group will be PCGT, which was initially developed for use as a control group in a VA multi-site study that tested the effects of Trauma-Focused Group Therapy. Correspondingly, PCGT serves as a credible control for the nonspecific effects of a group-based intervention (i.e. controls for time, attention, expectation of recovery, and recognition of the illness).<br>* Other names: PCGT;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Clinician Administered PTSD Scale | Clinician Administered PTSD Scale (CAPS) is a 17-item standard rating scale that measures PTSD severity with scores ranging from 0-136 (higher score = more severe). Scores of frequency and intensity are summed for the 17-items to yield the total CAPS score. | Baseline to week 9 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in PTSD Checklist (PCL) | PTSD Checklist (PCL) is a 17-item self-report scale intended to measure PTSD symptom severity. The PCL has demonstrated excellent internal consistency (alpha = .94-.97), and test-retest reliability over 2 to 3 days was .96 for Vietnam veterans. Respondents rate each item from 1 (not at all) to 5 (extremely) to indicate the degree to which they have been bothered by that particular symptom over the past month. Thus, total possible scores (items summed) range from 17 to 85 (higher score is more severe). A cut-off score of 50 indicates a probable diagnosis of PTSD. | Baseline to week 9 | 
| Change From Baseline in Five Facet Mindfulness Questionnaire (FFMQ) | Five Facet Mindfulness Questionnaire (FFMQ) is used to evaluate the effects of MBSR vs. PCGT on mindfulness (S1). The FFMQ is a 39-item self-report instrument that assesses the general tendency to be mindful in daily life through 5 facets: observing, describing, acting with awareness, non-judging of inner experience, non-reactivity to inner experience. Increases in FFMQ mediate improvements in well being in observational studies of MBSR. Each item is rated 1 to 5 (never or very rarely true to very often or always true). Some of the items are reverse scored (R). Scoring Information: Observe items:1, 6, 11, 15, 20, 26, 31, 36; Describe items: 2, 7, 12R, 16R, 22R, 27, 32, 37; Act with Awareness items: 5R, 8R, 13R, 18R, 23R, 28R, 34R, 38R; Nonjudge items: 3R, 10R, 14R, 17R, 25R, 30R, 35R, 39R; Nonreact items: 4, 9, 19, 21, 24, 29, 33. Total all subscales for score (higher score = greater degree of mindfulness). Score range 39-195 with higher=more mindfulness. | Baseline to week 9 | 
| Change From Baseline in Patient Health Questionnaire (PHQ-9) | Patient Health Questionnaire (PHQ-9) is a brief 9-item measure of depressive symptoms that has established reliability and validity in community and clinical populations. All items are summed for total score ranging from 0 to 27 (higher score = more severe depression). | Baseline to week 9 | 
| Change From Baseline in CAPS B Subscale | Clinician Administered PTSD Scale (CAPS) B subscale measures the re-experiencing cluster (i.e. B criterion) of PTSD symptoms and includes the first 5 items of the CAPS, which is a clinician-administered assessment of posttraumatic stress disorder (PTSD) symptoms. Frequency and intensity scores for each item is summed for a range of 0 to 40 (higher score = more severe PTSD). | Baseline to week 9 | 
| Change From Baseline in CAPS C Subscale | Clinician Administered PTSD Scale (CAPS) C subscale measures the avoidance and emotional numbing cluster (i.e. C criterion) of PTSD symptoms and includes the items 6 - 12 items of the CAPS, which is a clinician-administered assessment of posttraumatic stress disorder (PTSD) symptoms. Frequency and intensity scores for each item is summed for a range of 0 to 56 (higher score = more severe PTSD). | Baseline to week 9 | 
| Change From Baseline in CAPS D Subscale | Clinician Administered PTSD Scale (CAPS) D subscale measures the hyperarousal cluster (i.e. D criterion) of PTSD symptoms and includes the items 13 - 17 of the CAPS, which is a clinician-administered assessment of posttraumatic stress disorder (PTSD) symptoms. Frequency and intensity scores for each item is summed for a range of 0 to 40 (higher score = more severe PTSD). | Baseline to week 9 | 
| PTSD Response | Greater than or equal to 30% improvement on PTSD CAPS scale | Baseline to week 9 | 
| PTSD Remission | Total CAPS score of less than or equal to 45 at week 9 (single observation point) | Week 9 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Posttraumatic Stress Disorder, Meditation, Present Centered Group Therapy, mindfulness, MBSR, complementary alternative medicine