Clinical trial NCT02853032: Image-guided, Robotically Delivered Transcranial Magnetic Stimulation Treatment for Combat-Related Post-Traumatic Stress Disorder
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Stress Disorders, Post-Traumatic
Lead sponsor: The University of Texas Health Science Center at San Antonio
Sponsor class: OTHER
Collaborators: name: Laurel Ridge Treatment Center
name: Consortium to Alleviate PTSD
First posted: 2016-08-02
Enrollment: 119
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. 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;
2. Patients must have a diagnosis of PTSD confirmed by the Clinician-Administered PTSD Scale (CAPS-5) at screening,
3. Subjects must have a minimum PTSD Symptom Checklist (PCL-5) for DSM-V symptom severity rating of 25.

Exclusion Criteria:

1. Subjects with a diagnostic history of bipolar disorder, schizophrenia or schizoaffective disorder as documented in the medical record.
2. 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.
3. 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.
4. History of traumatic brain injury (TBI) with loss of consciousness for 20 minutes or more as determined by the History of Head Injuries questionnaire.
5. Females will be excluded if they are pregnant (i.e. positive pregnancy test identified after their LRTC intake).
6. 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.

Primary outcomes:
measure: Change in PTSD Severity as Measured by the PTSD Checklist (PCL-5)
timeFrame: Baseline to three weeks (the conclusion of rTMS treatment)
Secondary outcomes:
measure: Change in Depression Severity as Measured by the 9-item Patient Health Questionnaire (PHQ-9)
timeFrame: Baseline to three weeks (the conclusion of rTMS treatment)
measure: Change in Depression Severity as Measured by the Montgomery-Ashberg Depression Rating Scale (MADRS)
timeFrame: Baseline to three weeks (the conclusion of rTMS treatment)
measure: Change in PTSD Severity as Measured by the PTSD Checklist for DSM-5 (PCL-5)
timeFrame: Baseline to seven weeks (four weeks after the conclusion of rTMS treatment)
measure: Change in PTSD Severity as Measured by the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)
timeFrame: Baseline to seven weeks (four weeks after the conclusion of rTMS treatment)
measure: Change in Depression Severity as Measured by the 9-item Patient Health Questionnaire (PHQ-9)
timeFrame: Baseline to seven weeks (four weeks after the conclusion of rTMS treatment)
measure: Change in Depression Severity as Measured by the Montgomery-Ashberg Depression Rating Scale (MADRS)
timeFrame: Baseline to seven weeks (four weeks after the conclusion of rTMS treatment)
measure: Change in PTSD Severity as Measured by the PTSD Checklist for DSM-5 (PCL-5)
timeFrame: Baseline to sixteen weeks (twelve weeks after the conclusion of rTMS treatment)
measure: Change in PTSD Severity as Measured by the Clinician-Administered PTSD Scale (CAPS-5)
timeFrame: Baseline to sixteen weeks (twelve weeks after the conclusion of rTMS treatment)
measure: Change in Depression Severity as Measured by the 9-item Patient Health Questionnaire (PHQ-9)
timeFrame: Baseline to sixteen weeks (twelve weeks after the conclusion of rTMS treatment)
measure: Change in Depression Severity as Measured by the Montgomery-Ashberg Depression Rating Scale (MADRS)
timeFrame: Baseline to sixteen weeks (twelve weeks after the conclusion of rTMS treatment)
measure: Clinically Significant Response as Measured by the PTSD Checklist for DSM-5 (PCL-5)
timeFrame: Baseline to three weeks (the conclusion of rTMS treatment)
measure: Clinically Significant Response in Depression Severity as Measured by the 9-item Patient Health Questionnaire (PHQ-9)
timeFrame: Baseline to three weeks (the conclusion of rTMS treatment)
measure: Clinically Significant Response in Depression Severity as Measured by the Montgomery-Ashberg Depression Rating Scale (MADRS)
timeFrame: Baseline to three weeks (the conclusion of rTMS treatment)
measure: Clinically Significant Response as Measured by the PTSD Checklist for DSM-5 (PCL-5)
timeFrame: Baseline to seven weeks (four weeks after the conclusion of rTMS treatment)
measure: Clinically Significant Response as Measured by the Clinician-Administered PTSD Scale (CAPS-5)
timeFrame: Baseline to seven weeks (four weeks after the conclusion of rTMS treatment)
measure: Clinically Significant Response in Depression Severity as Measured by the 9-item Patient Health Questionnaire (PHQ-9)
timeFrame: Baseline to seven weeks (four weeks after the conclusion of rTMS treatment)
measure: Clinically Significant Response in Depression Severity as Measured by the Montgomery-Ashberg Depression Rating Scale (MADRS)
timeFrame: Baseline to seven weeks (four weeks after the conclusion of rTMS treatment)
measure: Clinically Significant Response as Measured by the PTSD Checklist for DSM-5 (PCL-5)
timeFrame: Baseline to sixteen weeks (twelve weeks after the conclusion of rTMS treatment)
measure: Clinically Significant Response as Measured by the Clinician-Administered PTSD Scale (CAPS-5)
timeFrame: Baseline to sixteen weeks (twelve weeks after the conclusion of rTMS treatment)
measure: Clinically Significant Response in Depression Severity as Measured by the 9-item Patient Health Questionnaire (PHQ-9)
timeFrame: Baseline to sixteen weeks (twelve weeks after the conclusion of rTMS treatment)
measure: Clinically Significant Response in Depression Severity as Measured by the Montgomery-Ashberg Depression Rating Scale (MADRS)
timeFrame: Baseline to sixteen weeks (twelve weeks after the conclusion of rTMS treatment)
measure: Remission From PTSD as Measured by the PTSD Checklist for DSM-5 (PCL-5)
timeFrame: Baseline to three weeks (the conclusion of rTMS treatment)
measure: Remission From Depression as Measured by the 9-item Patient Health Questionnaire (PHQ-9)
timeFrame: Baseline to three weeks (the conclusion of rTMS treatment)
measure: Remission From Depression as Measured by the Montgomery-Ashberg Depression Rating Scale (MADRS)
timeFrame: Baseline to three weeks (the conclusion of rTMS treatment)
measure: Remission From PTSD as Measured by the PTSD Checklist for DSM-5 (PCL-5)
timeFrame: Baseline to seven weeks (four weeks after the conclusion of rTMS treatment)
measure: Remission From PTSD as Measured by the Clinician-Administered PTSD Scale (CAPS-5)
timeFrame: Baseline to seven weeks (four weeks after the conclusion of rTMS treatment)
measure: Remission From Depression as Measured by the 9-item Patient Health Questionnaire (PHQ-9)
timeFrame: Baseline to seven weeks (four weeks after the conclusion of rTMS treatment)
measure: Remission From Depression as Measured by the Montgomery-Ashberg Depression Rating Scale (MADRS)
timeFrame: Baseline to seven weeks (four weeks after the conclusion of rTMS treatment)
measure: Remission From PTSD as Measured by the PTSD Checklist for DSM-5 (PCL-5)
timeFrame: Baseline to sixteen weeks (twelve weeks after the conclusion of rTMS treatment)
measure: Remission From PTSD as Measured by the Clinician-Administered PTSD Scale (CAPS-5)
timeFrame: Baseline to sixteen weeks (twelve weeks after the conclusion of rTMS treatment)
measure: Remission From Depression as Measured by the 9-item Patient Health Questionnaire (PHQ-9)
timeFrame: Baseline to sixteen weeks (twelve weeks after the conclusion of rTMS treatment)
measure: Remission From Depression as Measured by the Montgomery-Ashberg Depression Rating Scale (MADRS)
timeFrame: Baseline to sixteen weeks (twelve weeks after the conclusion of rTMS treatment)
measure: Functional Connectivity Changes (Measured by Resting-state Functional Magnetic Resonance Imaging) of the Targeted Brain Network(s) Following rTMS Treatment
timeFrame: Baseline to three weeks (the conclusion of rTMS treatment)
measure: Number of Participants With Treatment-emergent Adverse Events and Serious Adverse Events
timeFrame: Baseline to sixteen weeks (twelve weeks after the conclusion of rTMS treatment)
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: Laurel Ridge Treatment Center
state: Texas
Study officials:
affiliation: The University of Texas Health Science Center at San Antonio
name: Felipe S Salinas, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Boggio PS, Rocha M, Oliveira MO, Fecteau S, Cohen RB, Campanha C, Ferreira-Santos E, Meleiro A, Corchs F, Zaghi S, Pascual-Leone A, Fregni F. Noninvasive brain stimulation with high-frequency and low-intensity repetitive transcranial magnetic stimulation treatment for posttraumatic stress disorder. J Clin Psychiatry. 2010 Aug;71(8):992-9. doi: 10.4088/JCP.08m04638blu. Epub 2009 Dec 29.