Back to resultsrTMS for Orthopaedic Trauma Patients
Primary Purpose
Orthopaedic Trauma
Status
Withdrawn
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Accelerated intermittent theta burst treatment
Sponsored by
About this trial
This is an interventional treatment trial for Orthopaedic Trauma focused on measuring Depression, Transcranial Magnetic Stimulation (TMS), Theta Burst, Orthopaedic Trauma, Pain
Eligibility Criteria
Inclusion Criteria:
- Male or female, 18 to 65 years of age.
- Able to provide informed consent.
- Present to Stanford Emergency Department as a trauma with a major operative lower extremity injury
- Glasgow coma scale of 15 within 24 hours after admission or extubation
- Negative urinary toxicology screen for illicit substances;
- Negative pregnancy test if female and less then 60 y/o;
- No suspicion for a head injury and/or negative head CT scan for intracranial hemorrhage or injury based on standard of care
- No history of seizure disorder or other neurological disorders.
- All patients included must screen positive for PHQ-9 score >4 (positive symptoms of depression) and CES-T score <36 (poor coping self-efficacy).
Exclusion Criteria:
- Incarceration,
- Pregnant females,
- Prior psychotic disorder,
- Current use of anti-depressant or anti-psychotic medications,
- Prior-admission opioid use within 30 days (patients will be screened for recent prescription opioid use using the CURES report),
- Heavy alcohol use,
- Lesional neurological disorder or brain implant or intracranial ferromagnetic material,
- Seizure disorder
Sites / Locations
- Department of Orthopaedic Surgery, Stanford Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Accelerated intermittent theta burst treatment
Arm Description
All participants will receive accelerated intermittent theta-burst stimulation.
Outcomes
Primary Outcome Measures
Change from baseline in the Hospital Anxiety and Depression Scale (HADS)
The Hospital Anxiety and Depression Scale (HADS) (Zigmond & Snaith, 1983) is a 14-item measure designed to assess anxiety and depression symptoms in medical patients, with emphasis on reducing the impact of physical illness on the total score. The depression items tend to focus on the anhedonic symptoms of depression. Items are rated on a 4-point severity scale (0 to 3). Overall scores range from 0 to 42, with lower scores corresponding to fewer symptoms. The HADS produces two scales, one for anxiety (HADS-A) and one for depression (HADS-D), differentiating the two states; each subscale score ranges from 0 to 21, with lower scores corresponding to fewer symptoms. Scores of greater than or equal to 11 on either HADS-A or HADS-D scales indicate a definitive case of anxiety and/or depression, respectively.
Secondary Outcome Measures
Change from baseline in the Numeric Pain Rating Scale (NRS)
In a Numerical Rating Scale (NRS), patients are asked to make three pain ratings, corresponding to current, best and worst pain experienced over the past 24 hours.
The average of the 3 ratings is used to represent the patient's level of pain over the previous 24 hours.
Patients are asked to circle the number between 0 and 10 (first rating), 0 and 20 (second rating) and 0 and 100 (third rating) that fits best to their pain intensity. Zero usually represents 'no pain at all' whereas the upper limit represents 'the worst pain ever possible'.
Change from baseline in the PTSD Checklist for DSM-5 (PCL-5)
The PCL-5 is a 20-item self-report measure that assesses the 20 DSM-5 symptoms of PTSD. It takes approximately 5-10 minutes to complete. It uses a 5-point Likert scale (0 = "Not at all" to 4 = "Extremely") to rate symptoms of PTSD. Scores can range from 0 to 60, with a cut-off score of 33 indicating a provisional diagnosis of PTSD until further psychometric work is available.
The PCL-5 has a variety of purposes, including:
Monitoring symptom change during and after treatment
Screening individuals for PTSD
Making a provisional PTSD diagnosis
When necessary, the PCL-5 can be scored to provide a provisional PTSD diagnosis.
Change from baseline in the Trauma Coping Self-Efficacy (CSE-T) scale
9 item self-report scale designed to assess participants' capability of dealing with events following exposure to a traumatic event. Participants are asked to rate their ability from 1 "I'm not at all capable" to 7 "I'm totally capable". The lower the score, the more likely the participant is struggling to cope with their trauma.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03924024
Brief Title
rTMS for Orthopaedic Trauma Patients
Official Title
Repetitive Transcranial Magnetic Stimulation (rTMS) for Orthopaedic Trauma Patients
Study Type
Interventional
2. Study Status
Record Verification Date
May 2022
Overall Recruitment Status
Withdrawn
Why Stopped
We never started the study due to logistical limitations.
Study Start Date
August 1, 2019 (Actual)
Primary Completion Date
February 1, 2021 (Actual)
Study Completion Date
February 1, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Stanford University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study evaluates an accelerated schedule of theta-burst stimulation using a transcranial magnetic stimulation device for orthopaedic trauma patients. In this open label study, all participants will receive accelerated theta-burst stimulation. This study will examine whether symptoms of psychiatric distress and opioid use in orthopaedic trauma patients can be mitigated with rTMS to improve post-injury recovery.
Detailed Description
A large percentage of orthopaedic trauma patients suffer from psychiatric distress and chronic pain related to their injury and underlying psychosocial factors; this predicts poor post-injury recovery.
Repetitive transcranial magnetic stimulation (rTMS) is a neuromodulation technique used to stimulate areas of the brain that may modulate symptoms of pain, depression, and post-traumatic stress. The FDA-approved rTMS protocol for treatment is 10Hz stimulation for 40 minutes over the left dorsolateral prefrontal cortex (L-DLPFC) for the treatment of depression. This methodology has been very successful in real world situations, however poses some limitations, including the duration of the treatment session (approximately 40 minutes per treatment session). Recently, researchers have aggressively pursued modifying the treatment parameters to reduce treatment times with some preliminary success. This study will use modified parameters to create a more rapid form of treatment and look at outcome changes in pain and depression, commonly seen in orthopaedic trauma patients.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Orthopaedic Trauma
Keywords
Depression, Transcranial Magnetic Stimulation (TMS), Theta Burst, Orthopaedic Trauma, Pain
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Accelerated intermittent theta burst treatment
Arm Type
Experimental
Arm Description
All participants will receive accelerated intermittent theta-burst stimulation.
Intervention Type
Device
Intervention Name(s)
Accelerated intermittent theta burst treatment
Intervention Description
All participants will receive accelerated intermittent theta-burst stimulation to the left DLPFC. Stimulation intensity will be standardized to 80% of resting motor threshold.
Stimulation will be delivered to L-DLPFC using the Brainsway stimulator.
Primary Outcome Measure Information:
Title
Change from baseline in the Hospital Anxiety and Depression Scale (HADS)
Description
The Hospital Anxiety and Depression Scale (HADS) (Zigmond & Snaith, 1983) is a 14-item measure designed to assess anxiety and depression symptoms in medical patients, with emphasis on reducing the impact of physical illness on the total score. The depression items tend to focus on the anhedonic symptoms of depression. Items are rated on a 4-point severity scale (0 to 3). Overall scores range from 0 to 42, with lower scores corresponding to fewer symptoms. The HADS produces two scales, one for anxiety (HADS-A) and one for depression (HADS-D), differentiating the two states; each subscale score ranges from 0 to 21, with lower scores corresponding to fewer symptoms. Scores of greater than or equal to 11 on either HADS-A or HADS-D scales indicate a definitive case of anxiety and/or depression, respectively.
Time Frame
Baseline and immediate post-stimulation (up to 10 minutes to complete questionnaire)
Secondary Outcome Measure Information:
Title
Change from baseline in the Numeric Pain Rating Scale (NRS)
Description
In a Numerical Rating Scale (NRS), patients are asked to make three pain ratings, corresponding to current, best and worst pain experienced over the past 24 hours.
The average of the 3 ratings is used to represent the patient's level of pain over the previous 24 hours.
Patients are asked to circle the number between 0 and 10 (first rating), 0 and 20 (second rating) and 0 and 100 (third rating) that fits best to their pain intensity. Zero usually represents 'no pain at all' whereas the upper limit represents 'the worst pain ever possible'.
Time Frame
Baseline and immediate post-stimulation (up to 10 minutes to complete questionnaire)
Title
Change from baseline in the PTSD Checklist for DSM-5 (PCL-5)
Description
The PCL-5 is a 20-item self-report measure that assesses the 20 DSM-5 symptoms of PTSD. It takes approximately 5-10 minutes to complete. It uses a 5-point Likert scale (0 = "Not at all" to 4 = "Extremely") to rate symptoms of PTSD. Scores can range from 0 to 60, with a cut-off score of 33 indicating a provisional diagnosis of PTSD until further psychometric work is available.
The PCL-5 has a variety of purposes, including:
Monitoring symptom change during and after treatment
Screening individuals for PTSD
Making a provisional PTSD diagnosis
When necessary, the PCL-5 can be scored to provide a provisional PTSD diagnosis.
Time Frame
Baseline and immediate post-stimulation (up to 10 minutes to complete questionnaire)
Title
Change from baseline in the Trauma Coping Self-Efficacy (CSE-T) scale
Description
9 item self-report scale designed to assess participants' capability of dealing with events following exposure to a traumatic event. Participants are asked to rate their ability from 1 "I'm not at all capable" to 7 "I'm totally capable". The lower the score, the more likely the participant is struggling to cope with their trauma.
Time Frame
Baseline and immediate post-stimulation (up to 10 minutes to complete questionnaire)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female, 18 to 65 years of age.
Able to provide informed consent.
Present to Stanford Emergency Department as a trauma with a major operative lower extremity injury
Glasgow coma scale of 15 within 24 hours after admission or extubation
Negative urinary toxicology screen for illicit substances;
Negative pregnancy test if female and less then 60 y/o;
No suspicion for a head injury and/or negative head CT scan for intracranial hemorrhage or injury based on standard of care
No history of seizure disorder or other neurological disorders.
All patients included must screen positive for PHQ-9 score >4 (positive symptoms of depression) and CES-T score <36 (poor coping self-efficacy).
Exclusion Criteria:
Incarceration,
Pregnant females,
Prior psychotic disorder,
Current use of anti-depressant or anti-psychotic medications,
Prior-admission opioid use within 30 days (patients will be screened for recent prescription opioid use using the CURES report),
Heavy alcohol use,
Lesional neurological disorder or brain implant or intracranial ferromagnetic material,
Seizure disorder
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nolan Williams, MD
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Orthopaedic Surgery, Stanford Hospital
City
Palo Alto
State/Province
California
ZIP/Postal Code
94305
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
No plan to share data
Citations:
PubMed Identifier
20439832
Citation
George MS, Lisanby SH, Avery D, McDonald WM, Durkalski V, Pavlicova M, Anderson B, Nahas Z, Bulow P, Zarkowski P, Holtzheimer PE 3rd, Schwartz T, Sackeim HA. Daily left prefrontal transcranial magnetic stimulation therapy for major depressive disorder: a sham-controlled randomized trial. Arch Gen Psychiatry. 2010 May;67(5):507-16. doi: 10.1001/archgenpsychiatry.2010.46.
Results Reference
background
PubMed Identifier
8547583
Citation
George MS, Wassermann EM, Williams WA, Callahan A, Ketter TA, Basser P, Hallett M, Post RM. Daily repetitive transcranial magnetic stimulation (rTMS) improves mood in depression. Neuroreport. 1995 Oct 2;6(14):1853-6. doi: 10.1097/00001756-199510020-00008.
Results Reference
background
PubMed Identifier
8684201
Citation
Pascual-Leone A, Rubio B, Pallardo F, Catala MD. Rapid-rate transcranial magnetic stimulation of left dorsolateral prefrontal cortex in drug-resistant depression. Lancet. 1996 Jul 27;348(9022):233-7. doi: 10.1016/s0140-6736(96)01219-6.
Results Reference
background
PubMed Identifier
26850210
Citation
Chung SW, Hill AT, Rogasch NC, Hoy KE, Fitzgerald PB. Use of theta-burst stimulation in changing excitability of motor cortex: A systematic review and meta-analysis. Neurosci Biobehav Rev. 2016 Apr;63:43-64. doi: 10.1016/j.neubiorev.2016.01.008. Epub 2016 Feb 3.
Results Reference
background
PubMed Identifier
25281475
Citation
Jelic MB, Milanovic SD, Filipovic SR. Differential effects of facilitatory and inhibitory theta burst stimulation of the primary motor cortex on motor learning. Clin Neurophysiol. 2015 May;126(5):1016-23. doi: 10.1016/j.clinph.2014.09.003. Epub 2014 Sep 16.
Results Reference
background
PubMed Identifier
25450537
Citation
Chung SW, Hoy KE, Fitzgerald PB. Theta-burst stimulation: a new form of TMS treatment for depression? Depress Anxiety. 2015 Mar;32(3):182-92. doi: 10.1002/da.22335. Epub 2014 Nov 28.
Results Reference
background
PubMed Identifier
24411682
Citation
Plewnia C, Pasqualetti P, Grosse S, Schlipf S, Wasserka B, Zwissler B, Fallgatter A. Treatment of major depression with bilateral theta burst stimulation: a randomized controlled pilot trial. J Affect Disord. 2014 Mar;156:219-23. doi: 10.1016/j.jad.2013.12.025. Epub 2013 Dec 28.
Results Reference
background
PubMed Identifier
25430687
Citation
Prasser J, Schecklmann M, Poeppl TB, Frank E, Kreuzer PM, Hajak G, Rupprecht R, Landgrebe M, Langguth B. Bilateral prefrontal rTMS and theta burst TMS as an add-on treatment for depression: a randomized placebo controlled trial. World J Biol Psychiatry. 2015 Jan;16(1):57-65. doi: 10.3109/15622975.2014.964768. Epub 2014 Nov 28.
Results Reference
background
PubMed Identifier
24833712
Citation
Daskalakis ZJ. Theta-burst transcranial magnetic stimulation in depression: when less may be more. Brain. 2014 Jul;137(Pt 7):1860-2. doi: 10.1093/brain/awu123. Epub 2014 May 15. No abstract available.
Results Reference
background
PubMed Identifier
19862614
Citation
Thut G, Pascual-Leone A. A review of combined TMS-EEG studies to characterize lasting effects of repetitive TMS and assess their usefulness in cognitive and clinical neuroscience. Brain Topogr. 2010 Jan;22(4):219-32. doi: 10.1007/s10548-009-0115-4. Epub 2009 Oct 28.
Results Reference
background
PubMed Identifier
20734360
Citation
Holtzheimer PE 3rd, McDonald WM, Mufti M, Kelley ME, Quinn S, Corso G, Epstein CM. Accelerated repetitive transcranial magnetic stimulation for treatment-resistant depression. Depress Anxiety. 2010 Oct;27(10):960-3. doi: 10.1002/da.20731.
Results Reference
background
PubMed Identifier
24060620
Citation
Fung PK, Robinson PA. Neural field theory of synaptic metaplasticity with applications to theta burst stimulation. J Theor Biol. 2014 Jan 7;340:164-76. doi: 10.1016/j.jtbi.2013.09.021. Epub 2013 Sep 21.
Results Reference
background
PubMed Identifier
12506194
Citation
Greicius MD, Krasnow B, Reiss AL, Menon V. Functional connectivity in the resting brain: a network analysis of the default mode hypothesis. Proc Natl Acad Sci U S A. 2003 Jan 7;100(1):253-8. doi: 10.1073/pnas.0135058100. Epub 2002 Dec 27.
Results Reference
background
PubMed Identifier
18403396
Citation
Greicius MD, Supekar K, Menon V, Dougherty RF. Resting-state functional connectivity reflects structural connectivity in the default mode network. Cereb Cortex. 2009 Jan;19(1):72-8. doi: 10.1093/cercor/bhn059. Epub 2008 Apr 9.
Results Reference
background
PubMed Identifier
25770818
Citation
Hanlon CA, Dowdle LT, Austelle CW, DeVries W, Mithoefer O, Badran BW, George MS. What goes up, can come down: Novel brain stimulation paradigms may attenuate craving and craving-related neural circuitry in substance dependent individuals. Brain Res. 2015 Dec 2;1628(Pt A):199-209. doi: 10.1016/j.brainres.2015.02.053. Epub 2015 Mar 11.
Results Reference
background
PubMed Identifier
22444187
Citation
Taylor JJ, Borckardt JJ, George MS. Endogenous opioids mediate left dorsolateral prefrontal cortex rTMS-induced analgesia. Pain. 2012 Jun;153(6):1219-1225. doi: 10.1016/j.pain.2012.02.030. Epub 2012 Mar 22.
Results Reference
background
PubMed Identifier
16931989
Citation
Borckardt JJ, Weinstein M, Reeves ST, Kozel FA, Nahas Z, Smith AR, Byrne TK, Morgan K, George MS. Postoperative left prefrontal repetitive transcranial magnetic stimulation reduces patient-controlled analgesia use. Anesthesiology. 2006 Sep;105(3):557-62. doi: 10.1097/00000542-200609000-00020.
Results Reference
background
PubMed Identifier
17143157
Citation
Borckardt JJ, Smith AR, Hutcheson K, Johnson K, Nahas Z, Anderson B, Schneider MB, Reeves ST, George MS. Reducing pain and unpleasantness during repetitive transcranial magnetic stimulation. J ECT. 2006 Dec;22(4):259-64. doi: 10.1097/01.yct.0000244248.40662.9a.
Results Reference
background
PubMed Identifier
18080048
Citation
Borckardt JJ, Smith AR, Reeves ST, Weinstein M, Kozel FA, Nahas Z, Shelley N, Branham RK, Thomas KJ, George MS. Fifteen minutes of left prefrontal repetitive transcranial magnetic stimulation acutely increases thermal pain thresholds in healthy adults. Pain Res Manag. 2007 Winter;12(4):287-90. doi: 10.1155/2007/741897.
Results Reference
background
PubMed Identifier
19594842
Citation
Borckardt JJ, Smith AR, Reeves ST, Madan A, Shelley N, Branham R, Nahas Z, George MS. A pilot study investigating the effects of fast left prefrontal rTMS on chronic neuropathic pain. Pain Med. 2009 Jul-Aug;10(5):840-9. doi: 10.1111/j.1526-4637.2009.00657.x. Epub 2009 Jul 6.
Results Reference
background
PubMed Identifier
19759838
Citation
Borckardt JJ, Reeves ST, Weinstein M, Smith AR, Shelley N, Kozel FA, Nahas Z, Byrne KT, Morgan K, George MS. Significant analgesic effects of one session of postoperative left prefrontal cortex repetitive transcranial magnetic stimulation: a replication study. Brain Stimul. 2008 Apr;1(2):122-7. doi: 10.1016/j.brs.2008.04.002.
Results Reference
background
Learn more about this trial
rTMS for Orthopaedic Trauma Patients
We'll reach out to this number within 24 hrs