<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04497350</url>
  </required_header>
  <id_info>
    <org_study_id>20193262</org_study_id>
    <nct_id>NCT04497350</nct_id>
  </id_info>
  <brief_title>Transcranial Magnetic Stimulation vs Theta Burst Stimulation in Major Depressive Disorder</brief_title>
  <official_title>A Blinded, Randomized Trial Comparing the Effects of Transcranial Magnetic Stimulation and Theta Burst Stimulation in Patients With Major Depressive Disorder</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Neurological Associates of West Los Angeles</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Neurological Associates of West Los Angeles</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to investigate the differences in efficacy between transcranial&#xD;
      magnetic stimulation (TMS) and intermittent theta burst stimulation (iTBS) treatment in&#xD;
      subjects suffering from major depressive disorder.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Up to 30 patients of any gender aged from 18 to 70 years old will be recruited for inclusion&#xD;
      once candidacy has been established by screening criteria.&#xD;
&#xD;
      Once recruited, patients will be randomly assigned to the TMS treatment group or the iTBS&#xD;
      treatment group. Patients will be blinded to their group assignment, but will be informed of&#xD;
      their assignment upon the final outcome measure collection timepoint (e.g., 1 month&#xD;
      post-treatment). Patients who failed to respond by 1-month post iTBS or TMS treatment will be&#xD;
      allowed to cross-over into the other treatment group and will be re-enrolled into the study.&#xD;
&#xD;
      For patients assigned to the TMS treatment group, the treatment protocol will consist of 20&#xD;
      sessions of TMS treatment. Each TMS session will deliver 5,000 pulses (120-140% MT,&#xD;
      continuous temperature of 24C) over an 61 minute, 51 second time period. Patients will have&#xD;
      one TMS session per day, five days a week, until their treatment is completed (approximately&#xD;
      four weeks). Upon completion, the patient's depressive symptomatology and severity will be&#xD;
      assessed using the same outcome measures used at baseline.&#xD;
&#xD;
      For patients assigned to the iTBS treatment group, the treatment protocol will consist of 20&#xD;
      sessions of iTBS treatment. Each iTBS session will deliver 1,800 pulses (120-140% MT,&#xD;
      continuous temperature of 24C) over an 9-minute-40-second period. Patients will have up to&#xD;
      four iTBS sessions per day, five days a week, until their treatment is completed&#xD;
      (approximately 1 week). Upon completion, the patient's depressive symptomatology and severity&#xD;
      will be assessed using the same outcome measures used at baseline.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Enrolling by invitation</overall_status>
  <start_date type="Actual">January 6, 2020</start_date>
  <completion_date type="Anticipated">December 2024</completion_date>
  <primary_completion_date type="Anticipated">December 2023</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <intervention_model_description>This is a single-site, randomized, blinded, clinical trial comparing the efficacy of transcranial magnetic stimulation (TMS) and intermittent theta burst stimulation (iTBS) in subjects with treatment refractory depression (trMDD). The study will recruit 30 subjects, all suffering from treatment refractory depression (trMDD). Half of the subjects (15) will be randomized to the TMS treatment group, while the other half will be assigned to the iTBS treatment group. The randomization ratio will be 1:1.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Beck Depression Inventory (BDI-II)</measure>
    <time_frame>1 month</time_frame>
    <description>The BDI-II is a 21-question multiple-choice self-report inventory. Each question involves four possible responses, ranging in intensity from &quot;0&quot; (this item does not apply) to &quot;3&quot; (this item applies severely). The test is scored as the sum of all of the response values; this number is used to determine the severity of depressive symptoms. A score of 0 to 3 is possible for each question with a maximum total score of 63 points. The standard cutoff scores are as follows: 0-13 total points = minimal depression; 14-19 total points = mild depression; 20-28 total points = moderate depression; and 29-63 total points = severe depression. A reduction in the total score by at least 30% is considered to be clinically significant.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Patient Depression Questionnaire (PDQ-9)</measure>
    <time_frame>1 month</time_frame>
    <description>The PDQ-9 is a 9-item, self-report questionnaire to evaluate for depressive symptoms. Each question asks the patient if they have experienced a particular depressive symptom over the past two weeks. Answers may range from &quot;0&quot; (not at all), &quot;1&quot; (several days/week), &quot;2&quot; (more than half of the days), and &quot;3&quot; (nearly every day). Maximum total score is 27 points. A higher score indicates more severe depressive symptoms. A reduction in total score by at least 30% is considered clinically meaningful.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Hamilton Depression Rating Scale (HAM-D)</measure>
    <time_frame>1 month</time_frame>
    <description>The HAM-D is a 17-item, interview style questionnaire. A trained staff member administers this form to a patient and scores the patients' responses on a scale of &quot;0&quot; (symptom absent) to &quot;4&quot; (most severe option per symptom). A higher total score indicates a more severe level of depression. The maximum possible score is 50 points. A change in score of at least 30% is considered clinically meaningful.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Global Rating of Change (GRC)</measure>
    <time_frame>1 month</time_frame>
    <description>The GRC consists of a single likert-scale ranging from &quot;-5&quot; (very much worse) to &quot;0&quot; (neutral/no change) to &quot;5&quot; (very much better). The GRC is obtained in an interview format to assess a patient's perceived change in status following a treatment. A score that is at least 2 or greater is considered to indicate clinically significant change.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Beck Depression Inventory (BDI-II)</measure>
    <time_frame>2 months</time_frame>
    <description>The BDI-II is a 21-question multiple-choice self-report inventory. Each question involves four possible responses, ranging in intensity from &quot;0&quot; (this item does not apply) to &quot;3&quot; (this item applies severely). The test is scored as the sum of all of the response values; this number is used to determine the severity of depressive symptoms. A score of 0 to 3 is possible for each question with a maximum total score of 63 points. The standard cutoff scores are as follows: 0-13 total points = minimal depression; 14-19 total points = mild depression; 20-28 total points = moderate depression; and 29-63 total points = severe depression. A reduction in the total score by at least 30% is considered to be clinically significant.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient Depression Questionnaire (PDQ-9)</measure>
    <time_frame>2 months</time_frame>
    <description>The PDQ-9 is a 9-item, self-report questionnaire to evaluate for depressive symptoms. Each question asks the patient if they have experienced a particular depressive symptom over the past two weeks. Answers may range from &quot;0&quot; (not at all), &quot;1&quot; (several days/week), &quot;2&quot; (more than half of the days), and &quot;3&quot; (nearly every day). Maximum total score is 27 points. A higher score indicates more severe depressive symptoms. A reduction in total score by at least 30% is considered clinically meaningful.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hamilton Depression Rating Scale (HAM-D)</measure>
    <time_frame>2 months</time_frame>
    <description>The HAM-D is a 17-item, interview style questionnaire. A trained staff member administers this form to a patient and scores the patients' responses on a scale of &quot;0&quot; (symptom absent) to &quot;4&quot; (most severe option per symptom). A higher total score indicates a more severe level of depression. The maximum possible score is 50 points. A change in score of at least 30% is considered clinically meaningful.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Global Rating of Change (GRC)</measure>
    <time_frame>2 months</time_frame>
    <description>The GRC consists of a single likert-scale ranging from &quot;-5&quot; (very much worse) to &quot;0&quot; (neutral/no change) to &quot;5&quot; (very much better). The GRC is obtained in an interview format to assess a patient's perceived change in status following a treatment. A score that is at least 2 or greater is considered to indicate clinically significant change.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Major Depressive Disorder</condition>
  <arm_group>
    <arm_group_label>Transcranial Magnetic Stimulation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All patients are required to have an advanced MRI of the brain including a structural T1, volume measurements of various brain regions, ASL, and BOLD sequences. Patients will also undergo an in-scanner task designed to activate key neurofunctional regions of interest.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Theta Burst Stimulation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All patients are required to have an advanced MRI of the brain including a structural T1, volume measurements of various brain regions, ASL, and BOLD sequences. Patients will also undergo an in-scanner task designed to activate key neurofunctional regions of interest.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Transcranial Magnetic Stimulation</intervention_name>
    <description>5,000 pulses (120-140% MT, continuous temperature of 24C) will be delivered per session (see Appendix A for timing parameters). Patients will have one TMS session per day, five days a week, until their treatment is completed (approximately four weeks).</description>
    <arm_group_label>Transcranial Magnetic Stimulation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Theta Burst Stimulation</intervention_name>
    <description>One session of iTBS will deliver 1,800 pulses (120-140% MT, continuous temperature of 22ºC) over an 9-minute-40-second period. The minimum break period between iTBS sessions is 25 minutes.</description>
    <arm_group_label>Theta Burst Stimulation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of Major Depressive Disorder&#xD;
&#xD;
          -  Score greater than 13 on the Beck Depression Inventory&#xD;
&#xD;
          -  Failure to remit with 3 antidepressants&#xD;
&#xD;
          -  At least 18 years of age&#xD;
&#xD;
          -  Must be willing to comply with the study protocol&#xD;
&#xD;
          -  English Proficiency&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Hepatic impairment&#xD;
&#xD;
          -  Significant cytopenia&#xD;
&#xD;
          -  Cardiovascular, cerebrovascular, and peripheral vascular arterial thrombosis&#xD;
&#xD;
          -  Advanced terminal illness&#xD;
&#xD;
          -  Any active cancer or chemotherapy&#xD;
&#xD;
          -  Bone marrow disease&#xD;
&#xD;
          -  Neurodegenerative diseases&#xD;
&#xD;
          -  Myeloproliferative disorders&#xD;
&#xD;
          -  Sickle cell disease&#xD;
&#xD;
          -  Subjects with scalp rash or open wounds on the scalp&#xD;
&#xD;
          -  Women who are pregnant, may become pregnant, or are breastfeeding&#xD;
&#xD;
          -  Subjects unable to give informed consent or in vulnerable categories, such as&#xD;
             prisoners&#xD;
&#xD;
          -  Subjects who would not be able to lay down without excessive movement&#xD;
&#xD;
          -  Recent surgery or dental work within 3 months of the scheduled procedure&#xD;
&#xD;
          -  Not English Proficient&#xD;
&#xD;
          -  Advanced stages of any terminal illness or any active cancer that requires&#xD;
             chemotherapy&#xD;
&#xD;
          -  History of epilepsy or seizure, or history of such in first degree relative&#xD;
&#xD;
          -  An increased risk of seizure for any reason&#xD;
&#xD;
          -  Stents in the neck or brain&#xD;
&#xD;
          -  Aneurysm clips or coils&#xD;
&#xD;
          -  Metal devices/objects in or near the head&#xD;
&#xD;
          -  Metallic implants near the ears and eyes&#xD;
&#xD;
          -  Facial tattoos with metallic or magnetic-sensitive ink&#xD;
&#xD;
          -  Comorbid psychiatric conditions&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sheldon E Jordan, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Neurological Associates of West Los Angeles</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Neurological Associates of West Los Angeles</name>
      <address>
        <city>Santa Monica</city>
        <state>California</state>
        <zip>90403</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
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    <citation>Mayberg HS, Liotti M, Brannan SK, McGinnis S, Mahurin RK, Jerabek PA, Silva JA, Tekell JL, Martin CC, Lancaster JL, Fox PT. Reciprocal limbic-cortical function and negative mood: converging PET findings in depression and normal sadness. Am J Psychiatry. 1999 May;156(5):675-82. doi: 10.1176/ajp.156.5.675.</citation>
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    <citation>Botteron KN, Raichle ME, Drevets WC, Heath AC, Todd RD. Volumetric reduction in left subgenual prefrontal cortex in early onset depression. Biol Psychiatry. 2002 Feb 15;51(4):342-4. doi: 10.1016/s0006-3223(01)01280-x.</citation>
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    <citation>Yucel K, McKinnon M, Chahal R, Taylor V, Macdonald K, Joffe R, Macqueen G. Increased subgenual prefrontal cortex size in remitted patients with major depressive disorder. Psychiatry Res. 2009 Jul 15;173(1):71-6. doi: 10.1016/j.pscychresns.2008.07.013. Epub 2009 May 21.</citation>
    <PMID>19464154</PMID>
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    <citation>Rossi S, Hallett M, Rossini PM, Pascual-Leone A; Safety of TMS Consensus Group. Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol. 2009 Dec;120(12):2008-2039. doi: 10.1016/j.clinph.2009.08.016. Epub 2009 Oct 14.</citation>
    <PMID>19833552</PMID>
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    <citation>Daskalakis ZJ, Christensen BK, Fitzgerald PB, Chen R. Transcranial magnetic stimulation: a new investigational and treatment tool in psychiatry. J Neuropsychiatry Clin Neurosci. 2002 Fall;14(4):406-15. doi: 10.1176/jnp.14.4.406.</citation>
    <PMID>12426408</PMID>
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    <citation>Eldaief MC, Press DZ, Pascual-Leone A. Transcranial magnetic stimulation in neurology: A review of established and prospective applications. Neurol Clin Pract. 2013 Dec;3(6):519-526. doi: 10.1212/01.CPJ.0000436213.11132.8e.</citation>
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    <citation>Lefaucheur JP, Andre-Obadia N, Antal A, Ayache SS, Baeken C, Benninger DH, Cantello RM, Cincotta M, de Carvalho M, De Ridder D, Devanne H, Di Lazzaro V, Filipovic SR, Hummel FC, Jaaskelainen SK, Kimiskidis VK, Koch G, Langguth B, Nyffeler T, Oliviero A, Padberg F, Poulet E, Rossi S, Rossini PM, Rothwell JC, Schonfeldt-Lecuona C, Siebner HR, Slotema CW, Stagg CJ, Valls-Sole J, Ziemann U, Paulus W, Garcia-Larrea L. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS). Clin Neurophysiol. 2014 Nov;125(11):2150-2206. doi: 10.1016/j.clinph.2014.05.021. Epub 2014 Jun 5.</citation>
    <PMID>25034472</PMID>
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    <citation>Eldaief MC, Halko MA, Buckner RL, Pascual-Leone A. Transcranial magnetic stimulation modulates the brain's intrinsic activity in a frequency-dependent manner. Proc Natl Acad Sci U S A. 2011 Dec 27;108(52):21229-34. doi: 10.1073/pnas.1113103109. Epub 2011 Dec 12.</citation>
    <PMID>22160708</PMID>
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    <citation>Chen R, Classen J, Gerloff C, Celnik P, Wassermann EM, Hallett M, Cohen LG. Depression of motor cortex excitability by low-frequency transcranial magnetic stimulation. Neurology. 1997 May;48(5):1398-403. doi: 10.1212/wnl.48.5.1398.</citation>
    <PMID>9153480</PMID>
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  <reference>
    <citation>Pascual-Leone A, Valls-Sole J, Wassermann EM, Hallett M. Responses to rapid-rate transcranial magnetic stimulation of the human motor cortex. Brain. 1994 Aug;117 ( Pt 4):847-58. doi: 10.1093/brain/117.4.847.</citation>
    <PMID>7922470</PMID>
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    <citation>Strafella AP, Paus T, Barrett J, Dagher A. Repetitive transcranial magnetic stimulation of the human prefrontal cortex induces dopamine release in the caudate nucleus. J Neurosci. 2001 Aug 1;21(15):RC157. doi: 10.1523/JNEUROSCI.21-15-j0003.2001.</citation>
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    <citation>Larson J, Wong D, Lynch G. Patterned stimulation at the theta frequency is optimal for the induction of hippocampal long-term potentiation. Brain Res. 1986 Mar 19;368(2):347-50. doi: 10.1016/0006-8993(86)90579-2.</citation>
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    <citation>Kearney-Ramos TE, Dowdle LT, Lench DH, Mithoefer OJ, Devries WH, George MS, Anton RF, Hanlon CA. Transdiagnostic Effects of Ventromedial Prefrontal Cortex Transcranial Magnetic Stimulation on Cue Reactivity. Biol Psychiatry Cogn Neurosci Neuroimaging. 2018 Jul;3(7):599-609. doi: 10.1016/j.bpsc.2018.03.016. Epub 2018 Apr 10.</citation>
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    <citation>Oberman L, Edwards D, Eldaief M, Pascual-Leone A. Safety of theta burst transcranial magnetic stimulation: a systematic review of the literature. J Clin Neurophysiol. 2011 Feb;28(1):67-74. doi: 10.1097/WNP.0b013e318205135f.</citation>
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  <verification_date>September 2022</verification_date>
  <study_first_submitted>June 16, 2020</study_first_submitted>
  <study_first_submitted_qc>July 31, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 4, 2020</study_first_posted>
  <last_update_submitted>September 26, 2022</last_update_submitted>
  <last_update_submitted_qc>September 26, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 28, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>transcranial magnetic stimulation</keyword>
  <keyword>theta burst stimulation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Depressive Disorder</mesh_term>
    <mesh_term>Depression</mesh_term>
    <mesh_term>Depressive Disorder, Major</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Data from this study will not be made publicly available due to ethical and privacy concerns. Anonymized data will be available upon reasonable request from any qualified investigator.</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04497350
org study id: 20193262
nct id: NCT04497350
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: Yes
is us export: No
The purpose of this study is to investigate the differences in efficacy between transcranial
      magnetic stimulation (TMS) and intermittent theta burst stimulation (iTBS) treatment in
      subjects suffering from major depressive disorder.
Up to 30 patients of any gender aged from 18 to 70 years old will be recruited for inclusion
      once candidacy has been established by screening criteria.

      Once recruited, patients will be randomly assigned to the TMS treatment group or the iTBS
      treatment group. Patients will be blinded to their group assignment, but will be informed of
      their assignment upon the final outcome measure collection timepoint (e.g., 1 month
      post-treatment). Patients who failed to respond by 1-month post iTBS or TMS treatment will be
      allowed to cross-over into the other treatment group and will be re-enrolled into the study.

      For patients assigned to the TMS treatment group, the treatment protocol will consist of 20
      sessions of TMS treatment. Each TMS session will deliver 5,000 pulses (120-140% MT,
      continuous temperature of 24C) over an 61 minute, 51 second time period. Patients will have
      one TMS session per day, five days a week, until their treatment is completed (approximately
      four weeks). Upon completion, the patient's depressive symptomatology and severity will be
      assessed using the same outcome measures used at baseline.

      For patients assigned to the iTBS treatment group, the treatment protocol will consist of 20
      sessions of iTBS treatment. Each iTBS session will deliver 1,800 pulses (120-140% MT,
      continuous temperature of 24C) over an 9-minute-40-second period. Patients will have up to
      four iTBS sessions per day, five days a week, until their treatment is completed
      (approximately 1 week). Upon completion, the patient's depressive symptomatology and severity
      will be assessed using the same outcome measures used at baseline.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: This is a single-site, randomized, blinded, clinical trial comparing the efficacy of transcranial magnetic stimulation (TMS) and intermittent theta burst stimulation (iTBS) in subjects with treatment refractory depression (trMDD). The study will recruit 30 subjects, all suffering from treatment refractory depression (trMDD). Half of the subjects (15) will be randomized to the TMS treatment group, while the other half will be assigned to the iTBS treatment group. The randomization ratio will be 1:1.
primary purpose: Treatment
masking: Single (Participant)
measure: Beck Depression Inventory (BDI-II)
time frame: 1 month
description: The BDI-II is a 21-question multiple-choice self-report inventory. Each question involves four possible responses, ranging in intensity from "0" (this item does not apply) to "3" (this item applies severely). The test is scored as the sum of all of the response values; this number is used to determine the severity of depressive symptoms. A score of 0 to 3 is possible for each question with a maximum total score of 63 points. The standard cutoff scores are as follows: 0-13 total points = minimal depression; 14-19 total points = mild depression; 20-28 total points = moderate depression; and 29-63 total points = severe depression. A reduction in the total score by at least 30% is considered to be clinically significant.
measure: Patient Depression Questionnaire (PDQ-9)
time frame: 1 month
description: The PDQ-9 is a 9-item, self-report questionnaire to evaluate for depressive symptoms. Each question asks the patient if they have experienced a particular depressive symptom over the past two weeks. Answers may range from "0" (not at all), "1" (several days/week), "2" (more than half of the days), and "3" (nearly every day). Maximum total score is 27 points. A higher score indicates more severe depressive symptoms. A reduction in total score by at least 30% is considered clinically meaningful.
measure: Hamilton Depression Rating Scale (HAM-D)
time frame: 1 month
description: The HAM-D is a 17-item, interview style questionnaire. A trained staff member administers this form to a patient and scores the patients' responses on a scale of "0" (symptom absent) to "4" (most severe option per symptom). A higher total score indicates a more severe level of depression. The maximum possible score is 50 points. A change in score of at least 30% is considered clinically meaningful.
measure: Global Rating of Change (GRC)
time frame: 1 month
description: The GRC consists of a single likert-scale ranging from "-5" (very much worse) to "0" (neutral/no change) to "5" (very much better). The GRC is obtained in an interview format to assess a patient's perceived change in status following a treatment. A score that is at least 2 or greater is considered to indicate clinically significant change.
measure: Beck Depression Inventory (BDI-II)
time frame: 2 months
description: The BDI-II is a 21-question multiple-choice self-report inventory. Each question involves four possible responses, ranging in intensity from "0" (this item does not apply) to "3" (this item applies severely). The test is scored as the sum of all of the response values; this number is used to determine the severity of depressive symptoms. A score of 0 to 3 is possible for each question with a maximum total score of 63 points. The standard cutoff scores are as follows: 0-13 total points = minimal depression; 14-19 total points = mild depression; 20-28 total points = moderate depression; and 29-63 total points = severe depression. A reduction in the total score by at least 30% is considered to be clinically significant.
measure: Patient Depression Questionnaire (PDQ-9)
time frame: 2 months
description: The PDQ-9 is a 9-item, self-report questionnaire to evaluate for depressive symptoms. Each question asks the patient if they have experienced a particular depressive symptom over the past two weeks. Answers may range from "0" (not at all), "1" (several days/week), "2" (more than half of the days), and "3" (nearly every day). Maximum total score is 27 points. A higher score indicates more severe depressive symptoms. A reduction in total score by at least 30% is considered clinically meaningful.
measure: Hamilton Depression Rating Scale (HAM-D)
time frame: 2 months
description: The HAM-D is a 17-item, interview style questionnaire. A trained staff member administers this form to a patient and scores the patients' responses on a scale of "0" (symptom absent) to "4" (most severe option per symptom). A higher total score indicates a more severe level of depression. The maximum possible score is 50 points. A change in score of at least 30% is considered clinically meaningful.
measure: Global Rating of Change (GRC)
time frame: 2 months
description: The GRC consists of a single likert-scale ranging from "-5" (very much worse) to "0" (neutral/no change) to "5" (very much better). The GRC is obtained in an interview format to assess a patient's perceived change in status following a treatment. A score that is at least 2 or greater is considered to indicate clinically significant change.
arm group label: Transcranial Magnetic Stimulation
arm group type: Experimental
description: All patients are required to have an advanced MRI of the brain including a structural T1, volume measurements of various brain regions, ASL, and BOLD sequences. Patients will also undergo an in-scanner task designed to activate key neurofunctional regions of interest.
arm group label: Theta Burst Stimulation
arm group type: Experimental
description: All patients are required to have an advanced MRI of the brain including a structural T1, volume measurements of various brain regions, ASL, and BOLD sequences. Patients will also undergo an in-scanner task designed to activate key neurofunctional regions of interest.
intervention type: Device
intervention name: Transcranial Magnetic Stimulation
description: 5,000 pulses (120-140% MT, continuous temperature of 24C) will be delivered per session (see Appendix A for timing parameters). Patients will have one TMS session per day, five days a week, until their treatment is completed (approximately four weeks).
arm group label: Transcranial Magnetic Stimulation
intervention type: Device
intervention name: Theta Burst Stimulation
description: One session of iTBS will deliver 1,800 pulses (120-140% MT, continuous temperature of 22ºC) over an 9-minute-40-second period. The minimum break period between iTBS sessions is 25 minutes.
arm group label: Theta Burst Stimulation
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Sheldon E Jordan, M.D.
role: Principal Investigator
affiliation: Neurological Associates of West Los Angeles
facility: 
country: United States
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responsible party type: Sponsor
mesh term: Depressive Disorder
mesh term: Depression
mesh term: Depressive Disorder, Major
sharing ipd: No
ipd description: Data from this study will not be made publicly available due to ethical and privacy concerns. Anonymized data will be available upon reasonable request from any qualified investigator.