<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/NCT02190019</url>
  </required_header>
  <id_info>
    <org_study_id>391721</org_study_id>
    <nct_id>NCT02190019</nct_id>
  </id_info>
  <brief_title>Transcranial Magnetic Stimulation for Apathy in Mild Cognitive Impairment:Pilot Study</brief_title>
  <official_title>Transcranial Magnetic Stimulation for Apathy in Mild Cognitive Impairment:Pilot Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Central Arkansas Veterans Healthcare System</agency>
      <agency_class>U.S. Fed</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Central Arkansas Veterans Healthcare System</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Mild cognitive impairment (MCI) is a precursor of dementia. Apathy, a profound loss of&#xD;
      motivation, is a common behavioral problem in MCI. Presence of apathy may increase the chance&#xD;
      of MCI patients converting to Alzheimer's Dementia. Repetitive Transcranial Magnetic&#xD;
      Stimulation (rTMS), a non-invasive tool, has been recently approved for treatment of&#xD;
      refractory depression. Since dysfunction in the frontal lobe of the brain is seen in patients&#xD;
      with apathy, rTMS to the frontal lobe might be helpful in treating the same. Study hypotheses&#xD;
      include that rTMS to the dorsolateral prefrontal cortex (DLPFC) will improve apathy and&#xD;
      executive function better than sham treatment in those with MCI&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Objective: Mild cognitive impairment (MCI) is a precursor of dementia. Apathy, a profound&#xD;
      loss of motivation, is a common behavioral problem in MCI. Presence of apathy may increase&#xD;
      the chance of MCI patients converting to Alzheimer's Dementia. Repetitive Transcranial&#xD;
      Magnetic Stimulation (rTMS), a non-invasive tool, has been recently approved for treatment of&#xD;
      refractory depression. Since dysfunction in the frontal lobe of the brain is seen in patients&#xD;
      with apathy, rTMS to the frontal lobe might be helpful in treating the same.&#xD;
&#xD;
      Specific Aims:&#xD;
&#xD;
        -  To determine the efficacy of rTMS to the dorsolateral prefrontal cortex (DLPFC) in&#xD;
           treating apathy in MCI in comparison to sham treatment.&#xD;
&#xD;
        -  To compare the efficacy of rTMS to the DLPFC on executive function in MCI in comparison&#xD;
           to sham treatment.&#xD;
&#xD;
      Research Plan: Current study is a randomized sham controlled cross-over study of daily rTMS.&#xD;
&#xD;
      Methods: 20 subjects with MCI and apathy will be enrolled to randomize 8 to a total of 20&#xD;
      sessions of treatment (2 weeks sham, 2 weeks rTMS, with 4 weeks of washout period). Subjects&#xD;
      will be randomly assigned to rTMS or sham treatment after consent. After 2 weeks of treatment&#xD;
      there will be a 4 week period with no treatment. At the end of the 4-week wash out period,&#xD;
      subjects will be crossed over to the next treatment arm (i.e. those who received rTMS in the&#xD;
      beginning will receive sham treatment and vice versa). Subjects will be followed for four&#xD;
      additional weeks after treatment. Apathy will be assessed using the Apathy Evaluation Scale.&#xD;
      Memory, executive function, functional status and caregiver burden will be assessed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date>April 2014</start_date>
  <completion_date type="Anticipated">July 2016</completion_date>
  <primary_completion_date type="Actual">April 2015</primary_completion_date>
  <phase>Phase 4</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Apathy Evaluation Scale (AES)</measure>
    <time_frame>8 weeks</time_frame>
    <description>AES is an 18-item scale that assesses apathy in behavioral, cognitive and emotional domains over the previous four weeks.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Trials making test</measure>
    <time_frame>8 weeks</time_frame>
    <description>Widely used test for assessment of executive function.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Exit 25</measure>
    <time_frame>8 weeks</time_frame>
    <description>EXIT-25 is a bedside measure of executive function. It defines the behavioral sequelae of executive dyscontrol and provides a standardized clinical encounter in which they can be observed.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">14</enrollment>
  <condition>Apathy</condition>
  <condition>Mild Cognitive Impairment</condition>
  <arm_group>
    <arm_group_label>transcranial magnetic stimulator</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Neurostar repetitive transcranial magnetic stimulator. The active procedure will stimulate at 120% motor threshold for 4 seconds at a frequency of 10 Hz, with an inter-train interval of 26 seconds for a total of 3,000 pulses. 10 treatment sessions are given over a two week period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham coil treatment</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Neurostar repetitive transcranial magnetic stimulator. 10 treatments identical in duration will be administered over a two week period.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Neurostar repetitive transcranial magnetic stimulator</intervention_name>
    <description>The active procedure will stimulate at 120% motor threshold for 4 seconds at a frequency of 10 Hz, with an inter-train interval of 26 seconds for a total of 3,000 pulses. 10 treatment sessions are given over a two week period.</description>
    <arm_group_label>Sham coil treatment</arm_group_label>
    <arm_group_label>transcranial magnetic stimulator</arm_group_label>
    <other_name>rTMS</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Subjects age ≥ 55 years,&#xD;
&#xD;
          2. Subjects meeting Petersen's criteria for MCI,&#xD;
&#xD;
          3. Apathy Evaluation Scale-Clinician (AES-C) score of ≥ 30,&#xD;
&#xD;
          4. Mini Mentla Status Examination (MMSE) ≥ 23,&#xD;
&#xD;
          5. Subjects who clear the TMS adult safety scale (TASS)&#xD;
&#xD;
          6. On stable dose of antidepressants (if applicable) for at least two months&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subjects taking medications known to increase the risk of seizures from the 2012 Beers&#xD;
             criteria: Bupropion, chlorpromazine, clozapine, maprotiline, olanzapine, thioridazine,&#xD;
             thiothixene, and tramadol.&#xD;
&#xD;
          2. Subjects taking medications known to increase seizure threshold not listed in the&#xD;
             Beers criteria but in the opinion of PI increase seizure threshold: tricyclic&#xD;
             antidepressants, theophylline, methylphenidate, and high-dose thyroid supplementation.&#xD;
&#xD;
          3. Subjects taking ototoxic medications: Aminoglycosides, Cisplatin.&#xD;
&#xD;
          4. Subjects in current episode of major depression&#xD;
&#xD;
          5. History of bipolar disorder&#xD;
&#xD;
          6. Subjects with history of seizure or first degree relative with seizure disorder&#xD;
&#xD;
          7. Subjects with implanted device: wearable or implantable cardioverter defibrillators,&#xD;
             conductive, ferromagnetic, or other magnetic sensitive metals that are implanted or&#xD;
             are non-removable within 30 cm of the treatment coil or those with cochlear implants&#xD;
&#xD;
          8. Subjects with diagnosis of current alcohol related problems&#xD;
&#xD;
          9. Subjects with history of stroke , aneurysm, or cranial neurosurgery&#xD;
&#xD;
         10. Any condition that in the opinion of the study physician is likely to compromise their&#xD;
             ability to safely participate in the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>55 Years</minimum_age>
    <maximum_age>91 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Prasad R Padala, MD, MS</last_name>
    <role>Principal Investigator</role>
    <affiliation>Central Arkansas Veterans Healthcare System</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Central Arkansas Veterans Healthcare System</name>
      <address>
        <city>Little Rock</city>
        <state>Arkansas</state>
        <zip>72205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2016</verification_date>
  <study_first_submitted>July 11, 2014</study_first_submitted>
  <study_first_submitted_qc>July 14, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 15, 2014</study_first_posted>
  <last_update_submitted>February 9, 2016</last_update_submitted>
  <last_update_submitted_qc>February 9, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">February 10, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Central Arkansas Veterans Healthcare System</investigator_affiliation>
    <investigator_full_name>Prasad R. Padala</investigator_full_name>
    <investigator_title>Associate Director for Clinical Programs, GRECC</investigator_title>
  </responsible_party>
  <keyword>Mild Cognitive Impairment</keyword>
  <keyword>apathy</keyword>
  <keyword>executive function</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cognitive Dysfunction</mesh_term>
  </condition_browse>
  <pending_results>
    <submitted>January 23, 2018</submitted>
    <returned>March 1, 2018</returned>
    <submitted>August 20, 2019</submitted>
    <returned>September 12, 2019</returned>
    <submitted>July 13, 2020</submitted>
    <returned>July 24, 2020</returned>
  </pending_results>
  <!-- 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/NCT02190019
org study id: 391721
nct id: NCT02190019
lead sponsor: 
has dmc: No
Mild cognitive impairment (MCI) is a precursor of dementia. Apathy, a profound loss of
      motivation, is a common behavioral problem in MCI. Presence of apathy may increase the chance
      of MCI patients converting to Alzheimer's Dementia. Repetitive Transcranial Magnetic
      Stimulation (rTMS), a non-invasive tool, has been recently approved for treatment of
      refractory depression. Since dysfunction in the frontal lobe of the brain is seen in patients
      with apathy, rTMS to the frontal lobe might be helpful in treating the same. Study hypotheses
      include that rTMS to the dorsolateral prefrontal cortex (DLPFC) will improve apathy and
      executive function better than sham treatment in those with MCI
Objective: Mild cognitive impairment (MCI) is a precursor of dementia. Apathy, a profound
      loss of motivation, is a common behavioral problem in MCI. Presence of apathy may increase
      the chance of MCI patients converting to Alzheimer's Dementia. Repetitive Transcranial
      Magnetic Stimulation (rTMS), a non-invasive tool, has been recently approved for treatment of
      refractory depression. Since dysfunction in the frontal lobe of the brain is seen in patients
      with apathy, rTMS to the frontal lobe might be helpful in treating the same.

      Specific Aims:

        -  To determine the efficacy of rTMS to the dorsolateral prefrontal cortex (DLPFC) in
           treating apathy in MCI in comparison to sham treatment.

        -  To compare the efficacy of rTMS to the DLPFC on executive function in MCI in comparison
           to sham treatment.

      Research Plan: Current study is a randomized sham controlled cross-over study of daily rTMS.

      Methods: 20 subjects with MCI and apathy will be enrolled to randomize 8 to a total of 20
      sessions of treatment (2 weeks sham, 2 weeks rTMS, with 4 weeks of washout period). Subjects
      will be randomly assigned to rTMS or sham treatment after consent. After 2 weeks of treatment
      there will be a 4 week period with no treatment. At the end of the 4-week wash out period,
      subjects will be crossed over to the next treatment arm (i.e. those who received rTMS in the
      beginning will receive sham treatment and vice versa). Subjects will be followed for four
      additional weeks after treatment. Apathy will be assessed using the Apathy Evaluation Scale.
      Memory, executive function, functional status and caregiver burden will be assessed.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Apathy Evaluation Scale (AES)
time frame: 8 weeks
description: AES is an 18-item scale that assesses apathy in behavioral, cognitive and emotional domains over the previous four weeks.
measure: Trials making test
time frame: 8 weeks
description: Widely used test for assessment of executive function.
measure: Exit 25
time frame: 8 weeks
description: EXIT-25 is a bedside measure of executive function. It defines the behavioral sequelae of executive dyscontrol and provides a standardized clinical encounter in which they can be observed.
arm group label: transcranial magnetic stimulator
arm group type: Active Comparator
description: Neurostar repetitive transcranial magnetic stimulator. The active procedure will stimulate at 120% motor threshold for 4 seconds at a frequency of 10 Hz, with an inter-train interval of 26 seconds for a total of 3,000 pulses. 10 treatment sessions are given over a two week period.
arm group label: Sham coil treatment
arm group type: Sham Comparator
description: Neurostar repetitive transcranial magnetic stimulator. 10 treatments identical in duration will be administered over a two week period.
intervention type: Device
intervention name: Neurostar repetitive transcranial magnetic stimulator
description: The active procedure will stimulate at 120% motor threshold for 4 seconds at a frequency of 10 Hz, with an inter-train interval of 26 seconds for a total of 3,000 pulses. 10 treatment sessions are given over a two week period.
arm group label: Sham coil treatment
arm group label: transcranial magnetic stimulator
other name: rTMS
criteria: 
gender: All
minimum age: 55 Years
maximum age: 91 Years
healthy volunteers: No
last name: Prasad R Padala, MD, MS
role: Principal Investigator
affiliation: Central Arkansas Veterans Healthcare System
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Central Arkansas Veterans Healthcare System
investigator full name: Prasad R. Padala
investigator title: Associate Director for Clinical Programs, GRECC
mesh term: Cognitive Dysfunction
submitted: January 23, 2018
returned: March 1, 2018
submitted: August 20, 2019
returned: September 12, 2019
submitted: July 13, 2020
returned: July 24, 2020