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Image-guided, Robotically Delivered TMS Treatment for Combat-Related PTSD

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02853032
Recruitment Status : Completed
First Posted : August 2, 2016
Last Update Posted : September 24, 2019
Sponsor:
Collaborators:
Laurel Ridge Treatment Center
The Consortium to Alleviate PTSD
Information provided by (Responsible Party):
Felipe Salinas, The University of Texas Health Science Center at San Antonio

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.

Condition or disease Intervention/treatment Phase
Stress Disorders, Post-Traumatic Device: Active repetitive transcranial magnetic stimulation Device: robotic arm Device: Sham repetitive transcranial magnetic stimulation Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 129 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Image-guided, Robotically Delivered Transcranial Magnetic Stimulation Treatment for Combat-Related PTSD: a Double-Blind, Randomized Comparison to Sham TMS
Actual Study Start Date : July 5, 2017
Actual Primary Completion Date : March 25, 2019
Actual Study Completion Date : June 21, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Active rTMS to the right DLPFC
Active repetitive transcranial magnetic stimulation will be delivered to the right DLPFC using connectivity-based, image-guided aiming with the rTMS coil positioned using a robotic arm. In this arm, active rTMS will be delivered at 20 Hz in 2 sec trains with 28 sec inter-train intervals, 20 minutes/session (i.e. 1,600 pulses/session), 7 days/week for 20 consecutive days.
Device: Active repetitive transcranial magnetic stimulation
The MagPro R30 is an advanced, high performance magnetic stimulator designed primarily for non-invasive clinical use. The non-invasive brain stimulation system will be used to deliver active repetitive electromagnetic pulses in this research study's treatment of post-traumatic stress disorder.
Other Name: rTMS

Device: robotic arm
This robotic system is based on a commercially available neurosurgical robot. The robot is mounted on a mobile (i.e. retractable wheels) cart which holds the robot controller and the TMS power supply and pulse-generation computer. The robotic system will be used for TMS coil positioning/targeting.

Placebo Comparator: Sham rTMS to the right DLPFC
Sham repetitive transcranial magnetic stimulation will be delivered to the right DLPFC using connectivity-based, image-guided aiming with the rTMS coil positioned using a robotic arm. In this arm, sham rTMS will be delivered at 20 Hz in 2 sec trains with 28 sec inter-train intervals, 20 minutes/session (i.e. 1,600 pulses/session), 7 days/week for 20 consecutive days.
Device: robotic arm
This robotic system is based on a commercially available neurosurgical robot. The robot is mounted on a mobile (i.e. retractable wheels) cart which holds the robot controller and the TMS power supply and pulse-generation computer. The robotic system will be used for TMS coil positioning/targeting.

Device: Sham repetitive transcranial magnetic stimulation
The MagPro R30 is an advanced, high performance magnetic stimulator designed primarily for non-invasive clinical use. The non-invasive brain stimulation system will be used to deliver placebo repetitive electromagnetic pulses in this research study's treatment of post-traumatic stress disorder.
Other Name: sham rTMS




Primary Outcome Measures :
  1. Change in PTSD severity (PCL-5) [ Time Frame: Baseline to three weeks (the conclusion of rTMS treatment) ]
    Measured by the PTSD Checklist (PCL-5)


Secondary Outcome Measures :
  1. Change in depression severity (MADRS) [ Time Frame: Baseline to three weeks (the conclusion of rTMS treatment) ]
    Measured by the Montgomery-Ashberg Depression Rating Scale (MADRS)

  2. Change in depression severity (MADRS) [ Time Frame: Baseline to seven weeks (four weeks after the conclusion of rTMS treatment) ]
    Measured by the Montgomery-Ashberg Depression Rating Scale (MADRS)

  3. Change in depression severity (MADRS) [ Time Frame: Baseline to sixteen weeks (twelve weeks after the conclusion of rTMS treatment) ]
    Measured by the Montgomery-Ashberg Depression Rating Scale (MADRS)

  4. Change in PTSD severity (CAPS-5) [ Time Frame: Baseline to seven weeks (four weeks after the conclusion of rTMS treatment) ]
    Measured by the Clinician-Administered PTSD Scale (CAPS-5)

  5. Change in PTSD severity (CAPS-5) [ Time Frame: Baseline to sixteen weeks (twelve weeks after the conclusion of rTMS treatment) ]
    Measured by the Clinician-Administered PTSD Scale (CAPS-5)

  6. Change in PTSD severity (PCL-5) [ Time Frame: Baseline to seven weeks (four weeks after the conclusion of rTMS treatment) ]
    Measured by the PTSD Checklist (PCL-5)

  7. Change in PTSD severity (PCL-5) [ Time Frame: Baseline to sixteen weeks (twelve weeks after the conclusion of rTMS treatment) ]
    Measured by the PTSD Checklist (PCL-5)

  8. Clinically significant response (MADRS) [ Time Frame: Baseline to three weeks (the conclusion of rTMS treatment) ]
    Defined as greater than or equal to a 50% decrease in the Montgomery-Ashberg Depression Rating Scale

  9. Clinically significant response (MADRS) [ Time Frame: Baseline to seven weeks (four weeks after the conclusion of rTMS treatment) ]
    Defined as greater than or equal to a 50% decrease in the Montgomery-Ashberg Depression Rating Scale

  10. Clinically significant response (MADRS) [ Time Frame: Baseline to sixteen weeks (twelve weeks after the conclusion of rTMS treatment) ]
    Defined as greater than or equal to a 50% decrease in the Montgomery-Ashberg Depression Rating Scale

  11. Clinically significant response (CAPS-5) [ Time Frame: Baseline to seven weeks (four weeks after the conclusion of rTMS treatment) ]
    Defined as greater than or equal to a 50% decrease in the Clinician-Administered PTSD Scale (CAPS-5)

  12. Clinically significant response (CAPS-5) [ Time Frame: Baseline to sixteen weeks (twelve weeks after the conclusion of rTMS treatment) ]
    Defined as greater than or equal to a 50% decrease in the Clinician-Administered PTSD Scale (CAPS-5)

  13. Clinically significant response (PCL-5) [ Time Frame: Baseline to three weeks (the conclusion of rTMS treatment) ]
    Defined as a 10-20 point decrease in the PTSD Checklist (PCL-5) scores

  14. Clinically significant response (PCL-5) [ Time Frame: Baseline to seven weeks (four weeks after the conclusion of rTMS treatment) ]
    Defined as a 10-20 point decrease in the PTSD Checklist (PCL-5) scores

  15. Clinically significant response (PCL-5) [ Time Frame: Baseline to sixteen weeks (twelve weeks after the conclusion of rTMS treatment) ]
    Defined as a 10-20 point decrease in the PTSD Checklist (PCL-5) scores

  16. Remission from PTSD (CAPS-5) [ Time Frame: Baseline to seven weeks (four weeks after the conclusion of rTMS treatment) ]
    Defined as a Clinician-Administered PTSD Scale (CAPS-5) score less than or equal to 29

  17. Remission from PTSD (CAPS-5) [ Time Frame: Baseline to sixteen weeks (twelve weeks after the conclusion of rTMS treatment) ]
    Defined as a Clinician-Administered PTSD Scale (CAPS-5) score less than or equal to 29

  18. Remission from PTSD (PCL-5) [ Time Frame: Baseline to three weeks (the conclusion of rTMS treatment) ]
    Defined as a PTSD Checklist (PCL-5) score less than or equal to 33

  19. Remission from PTSD (PCL-5) [ Time Frame: Baseline to seven weeks (four weeks after the conclusion of rTMS treatment) ]
    Defined as a PTSD Checklist (PCL-5) score less than or equal to 33

  20. Remission from PTSD (PCL-5) [ Time Frame: Baseline to sixteen weeks (twelve weeks after the conclusion of rTMS treatment) ]
    Defined as a PTSD Checklist (PCL-5) score less than or equal to 33

  21. Remission from depression (MADRS) [ Time Frame: Baseline to three weeks (the conclusion of rTMS treatment) ]
    Defined as Montgomery-Ashberg Depression Rating Scale score less than or equal to 10

  22. Remission from depression (MADRS) [ Time Frame: Baseline to seven weeks (four weeks after the conclusion of rTMS treatment) ]
    Defined as Montgomery-Ashberg Depression Rating Scale score less than or equal to 10

  23. Remission from depression (MADRS) [ Time Frame: Baseline to sixteen weeks (twelve weeks after the conclusion of rTMS treatment) ]
    Defined as Montgomery-Ashberg Depression Rating Scale score less than or equal to 10

  24. Functional connectivity changes (measured by resting-state functional Magnetic Resonance Imaging) of the targeted brain network(s) following rTMS treatment [ Time Frame: Baseline to three weeks (the conclusion of rTMS treatment) ]
    Resting-state brain networks will be identified using functional Magnetic Resonance Imaging. Any changes in the the targeted brain network will be reported.

  25. Incidence of treatment-emergent adverse events and serious adverse events [ Time Frame: Baseline to sixteen weeks (twelve weeks after the conclusion of rTMS treatment) ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 for DSM-V (PCL-5) 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02853032


Locations
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United States, Texas
Laurel Ridge Treatment Center
San Antonio, Texas, United States, 78259
Sponsors and Collaborators
The University of Texas Health Science Center at San Antonio
Laurel Ridge Treatment Center
The Consortium to Alleviate PTSD
Investigators
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Principal Investigator: Felipe S Salinas, Ph.D. The University of Texas Health Science Center at San Antonio
Publications of Results:
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Responsible Party: Felipe Salinas, Research Scientist--Senior, The University of Texas Health Science Center at San Antonio
ClinicalTrials.gov Identifier: NCT02853032    
Other Study ID Numbers: HSC20160191H
First Posted: August 2, 2016    Key Record Dates
Last Update Posted: September 24, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: There is no plan to share individual participant data at this time.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Additional relevant MeSH terms:
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Stress Disorders, Post-Traumatic
Stress Disorders, Traumatic
Trauma and Stressor Related Disorders
Mental Disorders