Image-guided, Robotically Delivered Transcranial Magnetic Stimulation Treatment for Combat-Related Post-Traumatic Stress Disorder: a Double-Blind, Randomized Comparison to Sham Transcranial Magnetic Stimulation
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 119
- 试验地点
- 2
- 主要终点
- Change in PTSD Severity as Measured by the PTSD Checklist (PCL-5)
研究概览
简要总结
Mounting amounts of evidence suggests that non-invasive stimulation of the dorsolateral prefrontal cortex (DLPFC) using repetitive transcranial magnetic stimulation (rTMS) maybe a safe and effective treatment modality for Post-Traumatic Stress Disorder (PTSD). However the large variability in the magnitude of clinical outcomes reported is likely related to the current lack of knowledge of ideal side of stimulation (left vs right) and the limited precision in the targeting of brain circuits needed to obtain an optimal treatment response. In this protocol the investigators will: 1) generate individualized treatment plans based on an individual's functional Magnetic Resonance Imaging (fMRI) and meta-analytical based connectivity analysis to guide the delivery of adjunct, imaging-based & robotically delivered rTMS to active duty military (ADM) subjects with PTSD participating in an intensive program providing integrated evidence-based psychotherapy and pharmacological management (Treatment as Usual (TAU)). 2) To use clinician ratings and self-report PTSD symptom scales, as well as other indicators of clinical change, to determine whether compared with TAU, addition of adjunct rTMS improves clinical outcomes. 3) To conduct neuroimaging-based assessments aimed to measure rTMS effects on network connectivity in ADM receiving treatment for PTSD and the potential correlation of connectivity changes with clinical outcomes.
详细描述
The investigators propose a randomized, double-blind, sham-controlled, 20 consecutive day trial of adjunct rTMS to the right DLPFC for ADM with PTSD receiving TAU at Laurel Ridge Treatment Center (LRTC; San Antonio, TX). Methods: Consenting ADM receiving TAU for PTSD at LRTC will be randomized to receive 20 consecutive days of adjunct rTMS according to one of these two treatment arms: Arm 1 TAU plus rTMS to the right DLPFC and Arm 2 TAU plus sham rTMS. At UTHSCSA's Research Imaging Institute (RII), where all brain imaging will be conducted, rTMS treatment plans will be generated based on (pre-treatment) anatomical and functional magnetic resonance imaging (fMRI) to guide the optimal robotic positioning of the TMS coil to accurately target each subject's DLPFC. Initial diagnostic interview and weekly clinical follows ups will be conducted at the LRTC by research clinicians blinded to subjects' research group. A comparison of baseline brain connectivity measurements with subjects' neuroimaging follow ups conducted at treatment Week 3 will be conducted to identify network connectivity changes potentially associated to treatment response.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female English-speaking active duty or recently retired veteran patients who have deployed post 9/11 receiving treatment at LRTC between the ages of 18-65 years;
- •Patients must have a diagnosis of PTSD confirmed by the Clinician-Administered PTSD Scale (CAPS-5) at screening,
- •Subjects must have a minimum PTSD Symptom Checklist (PCL-5) for DSM-V symptom severity rating of 25.
排除标准
- •Subjects with a diagnostic history of bipolar disorder, schizophrenia or schizoaffective disorder as documented in the medical record.
- •Substance use disorder during the 12 months prior to screening; except that Mild - Moderate, but not Severe, Alcohol Use Disorder (using DSM-5 criteria) will be allowed as determined by LRTC medical provider review.
- •Any history or signs of serious medical or neurological illness including seizure disorders. Except for seizures, a subject with a clinical abnormality may be included only if the study clinician considers the illness will not introduce additional risk and will not interfere with the study procedures. This will be determined during the screening phase via self-report and/or medical history review.
- •History of traumatic brain injury (TBI) with loss of consciousness for 20 minutes or more as determined by the History of Head Injuries questionnaire.
- •Females will be excluded if they are pregnant (i.e. positive pregnancy test identified after their LRTC intake).
- •Any history or signs of metal objects deemed unsafe for MRI or that may adversely affect image quality of the brain region (e.g. surgical clips, cardiac pacemakers, metal implants, etc.) in the body at the time of screening as indicated by self-report. MRI can have risks for persons with foreign bodies implanted in their body.
结局指标
主要结局
Change in PTSD Severity as Measured by the PTSD Checklist (PCL-5)
时间窗: Baseline to three weeks (the conclusion of rTMS treatment)
The PCL-5 is a 20-item measure that assesses the presence and severity of PTSD symptoms. Responders are asked to rate how bothered they have been by each item in the past month on a 5-point Likert scale ranging from 0-4. Items are summed to provide a total score. Severity can be determined adding scores of each item together to determine a total score. The range is 0-80, with a lower score suggesting a lower incidence of PTSD. A total score of 33 or higher suggests the patient needs further assessment to confirm a diagnosis of PTSD.
次要结局
- Remission From Depression as Measured by the Montgomery-Ashberg Depression Rating Scale (MADRS)(Baseline to sixteen weeks (twelve weeks after the conclusion of rTMS treatment))
- Clinically Significant Response as Measured by the PTSD Checklist for DSM-5 (PCL-5)(Baseline to sixteen weeks (twelve weeks after the conclusion of rTMS treatment))
- Remission From Depression as Measured by the 9-item Patient Health Questionnaire (PHQ-9)(Baseline to sixteen weeks (twelve weeks after the conclusion of rTMS treatment))
- Change in Depression Severity as Measured by the 9-item Patient Health Questionnaire (PHQ-9)(Baseline to sixteen weeks (twelve weeks after the conclusion of rTMS treatment))
- Clinically Significant Response in Depression Severity as Measured by the Montgomery-Ashberg Depression Rating Scale (MADRS)(Baseline to sixteen weeks (twelve weeks after the conclusion of rTMS treatment))
- Remission From PTSD as Measured by the PTSD Checklist for DSM-5 (PCL-5)(Baseline to sixteen weeks (twelve weeks after the conclusion of rTMS treatment))
- Change in PTSD Severity as Measured by the PTSD Checklist for DSM-5 (PCL-5)(Baseline to sixteen weeks (twelve weeks after the conclusion of rTMS treatment))
- Change in PTSD Severity as Measured by the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)(Baseline to seven weeks (four weeks after the conclusion of rTMS treatment))
- Change in PTSD Severity as Measured by the Clinician-Administered PTSD Scale (CAPS-5)(Baseline to sixteen weeks (twelve weeks after the conclusion of rTMS treatment))
- Change in Depression Severity as Measured by the Montgomery-Ashberg Depression Rating Scale (MADRS)(Baseline to sixteen weeks (twelve weeks after the conclusion of rTMS treatment))
- Clinically Significant Response in Depression Severity as Measured by the 9-item Patient Health Questionnaire (PHQ-9)(Baseline to sixteen weeks (twelve weeks after the conclusion of rTMS treatment))
- Clinically Significant Response as Measured by the Clinician-Administered PTSD Scale (CAPS-5)(Baseline to sixteen weeks (twelve weeks after the conclusion of rTMS treatment))
- Remission From PTSD as Measured by the Clinician-Administered PTSD Scale (CAPS-5)(Baseline to sixteen weeks (twelve weeks after the conclusion of rTMS treatment))
- Number of Participants With Treatment-emergent Adverse Events and Serious Adverse Events(Baseline to sixteen weeks (twelve weeks after the conclusion of rTMS treatment))
- Functional Connectivity Changes (Measured by Resting-state Functional Magnetic Resonance Imaging) of the Targeted Brain Network(s) Following rTMS Treatment(Baseline to three weeks (the conclusion of rTMS treatment))
研究者
Felipe S. Salinas, Ph.D.
Assistant Professor--Research
The University of Texas Health Science Center at San Antonio