rTMS for Orthopaedic Trauma Patients

NCT03924024 | Withdrawn FDA Device

• 1 other identifier: 49006
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Orthopaedic Trauma

Keywords

Depression; Transcranial Magnetic Stimulation (TMS); Theta Burst; Orthopaedic Trauma; Pain

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline and immediate post-stimulation (up to 10 minutes to complete questionnaire)

Secondary Outcomes (3)

• Change from baseline in the Numeric Pain Rating Scale (NRS)

  Baseline and immediate post-stimulation (up to 10 minutes to complete questionnaire)

• Change from baseline in the PTSD Checklist for DSM-5 (PCL-5)

  Baseline and immediate post-stimulation (up to 10 minutes to complete questionnaire)

• Change from baseline in the Trauma Coping Self-Efficacy (CSE-T) scale

  Baseline and immediate post-stimulation (up to 10 minutes to complete questionnaire)

Study Arms (1)

Accelerated intermittent theta burst treatment

EXPERIMENTAL

All participants will receive accelerated intermittent theta-burst stimulation.

Device: Accelerated intermittent theta burst treatment

Interventions

Accelerated intermittent theta burst treatment DEVICE

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.

Accelerated intermittent theta burst treatment

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Department of Orthopaedic Surgery, Stanford Hospital

Palo Alto, California, 94305, United States

Location

Related Publications (21)

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• 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.

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• 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.

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• 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.

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• 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.

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• 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.

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• 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.

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• 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.

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• 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.

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• 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.

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• 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.

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• 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.

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• 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.

  PMID: 18080048 BACKGROUND

• 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.

  PMID: 19594842 BACKGROUND

• 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.

  PMID: 19759838 BACKGROUND

MeSH Terms

Conditions

Depression; Pain

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Nolan Williams, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, Director of Interventional Psychiatry Clinical Research, Department of Psychiatry and Behavioral Sciences, Stanford University Medical Center

Study Record Dates

• First Submitted: April 18, 2019
• First Posted: April 23, 2019
• Study Start: August 1, 2019
• Primary Completion: February 1, 2021
• Study Completion: February 1, 2021
• Last Updated: May 9, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)