<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/NCT01718730</url>
  </required_header>
  <id_info>
    <org_study_id>12-000335</org_study_id>
    <nct_id>NCT01718730</nct_id>
    <nct_alias>NCT00896090</nct_alias>
  </id_info>
  <brief_title>Cortical Excitability and Inhibition in MDD</brief_title>
  <official_title>Cortical Excitability and Inhibition in Children and Adolescents With Major Depressive Disorder</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mayo Clinic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Neuronetics</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Mayo Clinic</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_unapproved_device>Yes</is_unapproved_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to learn if measures of brain activity are different in children&#xD;
      and adolescents with depression who are in different stages of treatment. This is important&#xD;
      because it may identify a biological marker for depression that could one day be used to&#xD;
      identify depressed children who would benefit from certain treatments (medications for&#xD;
      example), or to monitor how well treatments are working. Brain activity measures(known as&#xD;
      cortical excitability and inhibition) will be collected by Transcranial Magnetic Stimulation&#xD;
      (TMS). TMS is a noninvasive (no surgery or implants) brain stimulation technology which can&#xD;
      make parts of the brain work without putting any wires or chemicals into the body.&#xD;
      Measurements will take place over one 3-hour visit. This study does not provide any form of&#xD;
      treatment.&#xD;
&#xD;
      *There is an optional portion of the study that uses a brain scan to gather measures of brain&#xD;
      structure and brain chemicals. The brain scan is called magnetic resonance and spectroscopy&#xD;
      (MRI/MRS). MRI/MRS uses magnetic fields to study the structure of the brain and brain&#xD;
      chemicals. The PI will determine eligibility for the MRI/MRS portion of the study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is focused on understanding the neurophysiology of major depressive disorder&#xD;
      (MDD), and the impact of selective serotonin reuptake inhibitors (SSRIs) in children and&#xD;
      adolescents. This is a cross-sectional study which will utilize single and paired-pulse&#xD;
      transcranial magnetic stimulation (TMS) to collect measures of glutamatergic cortical&#xD;
      excitability (the motor threshold and intracortical facilitation), and GABAergic cortical&#xD;
      inhibition (the cortical silent period and intracortical inhibition) of the motor cortex in&#xD;
      chilren and adolescents in various disease states of MDD. The optional proton magnetic&#xD;
      resonance spectroscopy and imaging scans (MRS/MRI) at 3 Tesla (3T) will examine glutamate&#xD;
      concentrations in the motor cortex and anterior cingulate cortex.&#xD;
&#xD;
      This is a biomarker study (MRI/MRS and TMS neurophysiology measures); treatment is not&#xD;
      provided in any form. This study will not utilize Repetitive Transcranial Magnetic&#xD;
      Stimulation (rTMS).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">August 2019</completion_date>
  <primary_completion_date type="Actual">August 2019</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Cortical Excitability and Inhibition at Motor Cortex</measure>
    <time_frame>Baseline</time_frame>
    <description>Motor Threshold (MT) is a single-pulse TMS measure of cortical excitability. A higher MT indicates decreased cortical excitability. Intracortical Facilitation (ICF) is a paired-pulse TMS measure of cortical excitability. A higher ICF indicates increased cortical excitability. Cortical Silent Period (CSP) is a single-pulse TMS measure of cortical inhibition. Longer CSP durations indicate greater cortical inhibition. Intracortical Inhibition (ICI) is a paired pulse TMS measure of cortical inhibition. A lower ICI indicates increased cortical inhibition, and a higher ICI indicates decreased cortical inhibition.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Glutamate Concentrations in the Motor Cortex and Anterior Cingulate Cortex</measure>
    <time_frame>Baseline</time_frame>
    <description>Glutamate concentrations will be measured with proton magnetic resonance imaging at 3T.</description>
  </secondary_outcome>
  <number_of_groups>4</number_of_groups>
  <enrollment type="Actual">23</enrollment>
  <condition>Major Depressive Disorder, Recurrent, Mild</condition>
  <condition>Depressive Disorder, Major</condition>
  <arm_group>
    <arm_group_label>Mild depression</arm_group_label>
    <description>Subjects with mild, but clinically significant depression</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Moderate to Severe MDD</arm_group_label>
    <description>Subjects with moderate to severe major depressive disorder who have not yet initiated treatment with an SSRI</description>
  </arm_group>
  <arm_group>
    <arm_group_label>MDD with response to SSRI</arm_group_label>
    <description>Subjects with moderate to severe major depressive disorder that has responded to an SSRI</description>
  </arm_group>
  <arm_group>
    <arm_group_label>MDD without response to SSRI</arm_group_label>
    <description>Subjects with moderate to severe major depressive disorder which has not responded to treatment with an SSRI</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Transcranial Magnetic Stimulation (TMS)</intervention_name>
    <description>Single and paired-pulse TMS applied to the motor cortex will collect measures of cortical excitability and inhibition.</description>
    <arm_group_label>MDD with response to SSRI</arm_group_label>
    <arm_group_label>MDD without response to SSRI</arm_group_label>
    <arm_group_label>Mild depression</arm_group_label>
    <arm_group_label>Moderate to Severe MDD</arm_group_label>
    <other_name>Device: Magstim Model 200</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Magnetic Resonance Spectroscopy and Imaging</intervention_name>
    <description>MRS/MRI Scans will examine glutamate concentrations in the motor cortex and anterior cingulate cortex.</description>
    <arm_group_label>MDD with response to SSRI</arm_group_label>
    <arm_group_label>MDD without response to SSRI</arm_group_label>
    <arm_group_label>Mild depression</arm_group_label>
    <arm_group_label>Moderate to Severe MDD</arm_group_label>
    <other_name>MRS/MRI</other_name>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        This protocol will plan to screen depressed children and adolescents who are seeking&#xD;
        treatment at Mayo Clinic in Rochester, MN, using strict inclusion and exclusion criteria.&#xD;
        These adolescents will represent gender and minority distribution consistent with the&#xD;
        Rochester metro/rural area demographic distribution. This study will be inclusive of all&#xD;
        races, genders, and socioeconomic classes.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adolescents from the ages of 13 to 21, male or female.&#xD;
&#xD;
          -  Subjects with MDD (groups 2, 3, and 4):&#xD;
&#xD;
          -  Must have a Children's Depression Rating Scale, Revised (CDRS-R) score of 40 or higher&#xD;
&#xD;
          -  Must have a Clinical Global Impression-Severity scale (CGI-S) score of 4 or higher.&#xD;
&#xD;
          -  Group 1: (50 subjects): Subjects who have mild (CDRS-R score &lt; 40) but clinically&#xD;
             significant depression.&#xD;
&#xD;
          -  Group 2: (50 subjects): Subjects with moderate to severe MDD who have not yet&#xD;
             initiated treatment with an SSRI.&#xD;
&#xD;
          -  Group 3: (50 subjects): Subjects with moderate to severe MDD that has responded to&#xD;
             treatment with an SSRI.&#xD;
&#xD;
          -  Group 4: (50 subjects): Subjects with moderate to severe MDD which has not responded&#xD;
             to treatment with an SSRI.&#xD;
&#xD;
          -  Capable of providing informed assent (consent if age 18) in addition to consent by&#xD;
             parent or guardian.&#xD;
&#xD;
          -  Subjects and at least 1 parent must be fluent in English.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Primary Axis I or II disorder other than MDD.&#xD;
&#xD;
          -  Unprovoked seizure history, seizure disorder, history of febrile seizures, family&#xD;
             history of epilepsy.&#xD;
&#xD;
          -  Any significant findings on the TMS Adult Safety Screen (TASS) or contraindications to&#xD;
             MRI/MRS&#xD;
&#xD;
          -  Subjects who are judged by the Principal Investigator to be at imminent risk for self&#xD;
             harm or suicide as indicated by interview or C-SSRS.&#xD;
&#xD;
          -  Pregnancy or suspected pregnancy in females.&#xD;
&#xD;
          -  Metal in the head (except the mouth*), implanted medication pumps, cardiac pacemaker.&#xD;
&#xD;
             * Subjects with braces will be excluded from MRI/MRS portion of study only&#xD;
&#xD;
          -  Prior brain surgery.&#xD;
&#xD;
          -  Risk for increased intracranial pressure such as a brain tumor.&#xD;
&#xD;
          -  Any unstable medical condition.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>13 Years</minimum_age>
    <maximum_age>21 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Paul E Croarkin, D.O.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mayo Clinic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.mayo.edu/research/clinical-trials</url>
    <description>Mayo Clinic Clinical Trials</description>
  </link>
  <verification_date>October 2019</verification_date>
  <study_first_submitted>October 29, 2012</study_first_submitted>
  <study_first_submitted_qc>October 29, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 31, 2012</study_first_posted>
  <last_update_submitted>October 20, 2019</last_update_submitted>
  <last_update_submitted_qc>October 20, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">October 22, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Mayo Clinic</investigator_affiliation>
    <investigator_full_name>Paul E. Croarkin</investigator_full_name>
    <investigator_title>PI</investigator_title>
  </responsible_party>
  <keyword>TMS</keyword>
  <keyword>Adolescent</keyword>
  <keyword>Child</keyword>
  <keyword>MDD</keyword>
  <keyword>Major depressive disorder</keyword>
  <keyword>Mild MDD</keyword>
  <keyword>Mild depression</keyword>
  <keyword>SSRI</keyword>
  <keyword>Motor cortex</keyword>
  <keyword>Cortical excitability</keyword>
  <keyword>Cortical inhibition</keyword>
  <keyword>Cortical silent period</keyword>
  <keyword>Motor threshold</keyword>
  <keyword>Intracortical facilitation</keyword>
  <keyword>Intracortical inhibition</keyword>
  <keyword>gamma-aminobutyric acid (GABA)</keyword>
  <keyword>Glutamate</keyword>
  <keyword>N-methyl-D-aspartate (NMDA)</keyword>
  <keyword>Magnetic resonance spectroscopy</keyword>
  <keyword>MRS</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>
  </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/NCT01718730
org study id: 12-000335
nct id: NCT01718730
nct alias: NCT00896090
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: Yes
is unapproved device: Yes
The purpose of this study is to learn if measures of brain activity are different in children
      and adolescents with depression who are in different stages of treatment. This is important
      because it may identify a biological marker for depression that could one day be used to
      identify depressed children who would benefit from certain treatments (medications for
      example), or to monitor how well treatments are working. Brain activity measures(known as
      cortical excitability and inhibition) will be collected by Transcranial Magnetic Stimulation
      (TMS). TMS is a noninvasive (no surgery or implants) brain stimulation technology which can
      make parts of the brain work without putting any wires or chemicals into the body.
      Measurements will take place over one 3-hour visit. This study does not provide any form of
      treatment.

      *There is an optional portion of the study that uses a brain scan to gather measures of brain
      structure and brain chemicals. The brain scan is called magnetic resonance and spectroscopy
      (MRI/MRS). MRI/MRS uses magnetic fields to study the structure of the brain and brain
      chemicals. The PI will determine eligibility for the MRI/MRS portion of the study.
This study is focused on understanding the neurophysiology of major depressive disorder
      (MDD), and the impact of selective serotonin reuptake inhibitors (SSRIs) in children and
      adolescents. This is a cross-sectional study which will utilize single and paired-pulse
      transcranial magnetic stimulation (TMS) to collect measures of glutamatergic cortical
      excitability (the motor threshold and intracortical facilitation), and GABAergic cortical
      inhibition (the cortical silent period and intracortical inhibition) of the motor cortex in
      chilren and adolescents in various disease states of MDD. The optional proton magnetic
      resonance spectroscopy and imaging scans (MRS/MRI) at 3 Tesla (3T) will examine glutamate
      concentrations in the motor cortex and anterior cingulate cortex.

      This is a biomarker study (MRI/MRS and TMS neurophysiology measures); treatment is not
      provided in any form. This study will not utilize Repetitive Transcranial Magnetic
      Stimulation (rTMS).
observational model: Case-Control
time perspective: Cross-Sectional
measure: Cortical Excitability and Inhibition at Motor Cortex
time frame: Baseline
description: Motor Threshold (MT) is a single-pulse TMS measure of cortical excitability. A higher MT indicates decreased cortical excitability. Intracortical Facilitation (ICF) is a paired-pulse TMS measure of cortical excitability. A higher ICF indicates increased cortical excitability. Cortical Silent Period (CSP) is a single-pulse TMS measure of cortical inhibition. Longer CSP durations indicate greater cortical inhibition. Intracortical Inhibition (ICI) is a paired pulse TMS measure of cortical inhibition. A lower ICI indicates increased cortical inhibition, and a higher ICI indicates decreased cortical inhibition.
measure: Glutamate Concentrations in the Motor Cortex and Anterior Cingulate Cortex
time frame: Baseline
description: Glutamate concentrations will be measured with proton magnetic resonance imaging at 3T.
arm group label: Mild depression
description: Subjects with mild, but clinically significant depression
arm group label: Moderate to Severe MDD
description: Subjects with moderate to severe major depressive disorder who have not yet initiated treatment with an SSRI
arm group label: MDD with response to SSRI
description: Subjects with moderate to severe major depressive disorder that has responded to an SSRI
arm group label: MDD without response to SSRI
description: Subjects with moderate to severe major depressive disorder which has not responded to treatment with an SSRI
intervention type: Device
intervention name: Transcranial Magnetic Stimulation (TMS)
description: Single and paired-pulse TMS applied to the motor cortex will collect measures of cortical excitability and inhibition.
arm group label: MDD with response to SSRI
arm group label: MDD without response to SSRI
arm group label: Mild depression
arm group label: Moderate to Severe MDD
other name: Device: Magstim Model 200
intervention type: Device
intervention name: Magnetic Resonance Spectroscopy and Imaging
description: MRS/MRI Scans will examine glutamate concentrations in the motor cortex and anterior cingulate cortex.
arm group label: MDD with response to SSRI
arm group label: MDD without response to SSRI
arm group label: Mild depression
arm group label: Moderate to Severe MDD
other name: MRS/MRI
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 13 Years
maximum age: 21 Years
healthy volunteers: No
last name: Paul E Croarkin, D.O.
role: Principal Investigator
affiliation: Mayo Clinic
facility: 
country: United States
url: https://www.mayo.edu/research/clinical-trials
description: Mayo Clinic Clinical Trials
responsible party type: Principal Investigator
investigator affiliation: Mayo Clinic
investigator full name: Paul E. Croarkin
investigator title: PI
mesh term: Depressive Disorder
mesh term: Depression
mesh term: Depressive Disorder, Major
sharing ipd: No