<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/NCT02190084</url>
  </required_header>
  <id_info>
    <org_study_id>547461</org_study_id>
    <nct_id>NCT02190084</nct_id>
  </id_info>
  <brief_title>Repetitive Transcranial Magnetic Stimulation for Apathy in Alzheimer's Dementia</brief_title>
  <official_title>Repetitive Transcranial Magnetic Stimulation for Apathy in Alzheimer's Dementia</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>
      Alzheimer's Dementia (AD) is a major public health problem. Apathy, a profound loss of&#xD;
      motivation, is seen in majority of patients with AD. Dysfunction of the front of the brain&#xD;
      and loss of dopamine, a type of neurochemical, in this part of brain results in apathy.&#xD;
      Presence of apathy is linked to deficits in planning sequential tasks such as keeping a&#xD;
      routine. Patients with apathy have poor physical function and their caregivers experience&#xD;
      extra burden. Unfortunately there are no good medications to treat apathy. FDA has approved&#xD;
      the use of brain stimulation by a magnet known as repetitive transcranial magnetic&#xD;
      stimulation (rTMS), for treatment of depression. rTMS increases dopamine when applied to&#xD;
      frontal lobe of brain so we propose that rTMS would be a good treatment option for apathy in&#xD;
      AD. Study hypotheses include that rTMS to the dorsolateral prefrontal cortex (DLPFC) will&#xD;
      improve apathy and executive function better than sham treatment in those with AD.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Objective: Alzheimer's Dementia (AD) is a major public health problem. Apathy, a profound&#xD;
      loss of motivation, is seen in majority of patients with AD. Dysfunction of the front of the&#xD;
      brain and loss of dopamine, a type of neurochemical, in this part of brain results in apathy.&#xD;
      Presence of apathy is linked to deficits in planning sequential tasks such as keeping a&#xD;
      routine. Patients with apathy have poor physical function and their caregivers experience&#xD;
      extra burden. Unfortunately there are no good medications to treat apathy. FDA has approved&#xD;
      the use of brain stimulation by a magnet known as repetitive transcranial magnetic&#xD;
      stimulation (rTMS), for treatment of depression. rTMS increases dopamine when applied to&#xD;
      frontal lobe of brain so we propose that rTMS would be a good treatment option for apathy in&#xD;
      AD.&#xD;
&#xD;
      Specific Aims: To determine the efficacy of rTMS to the dorsolateral prefrontal cortex&#xD;
      (DLPFC) in treating apathy in mild AD in comparison to sham treatment.&#xD;
&#xD;
      • To compare the efficacy of rTMS to the DLPFC on executive function in mild AD in comparison&#xD;
      to sham treatment.&#xD;
&#xD;
      Research Plan: Current study is a prospective randomized sham controlled study of daily rTMS.&#xD;
&#xD;
      Methods: Up to 500 subjects will be pre-screened to enroll 100 subjects for screening and&#xD;
      randomizing up to 50 subjects to analyze 20 completers. Subjects with mild AD and apathy will&#xD;
      be randomly assigned to rTMS or sham treatment after consent. All subjects will be tested for&#xD;
      memory, behavioral problems, functioning and caregiver burden. Apathy will be assessed using&#xD;
      the Apathy Evaluation Scale. Memory, executive function, functional status and caregiver&#xD;
      burden will be assessed. Subjects will receive daily treatments for 4 weeks with either rTMS&#xD;
      or sham coil for a total of 20 treatments. Neither the subject nor the investigators will&#xD;
      know which treatment the subject is receiving. Testing will be repeated at the end of 4 weeks&#xD;
      and at 8 and 12 weeks after treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 2014</start_date>
  <completion_date type="Actual">July 2019</completion_date>
  <primary_completion_date type="Actual">May 2019</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>Parallel 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>4 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>4 weeks</time_frame>
    <description>Widely used test for assessment of executive function.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Exit 25</measure>
    <time_frame>4 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">20</enrollment>
  <condition>Apathy</condition>
  <condition>Alzheimer's Dementia</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. 20 treatment sessions are given over a four 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. 20 treatments identical in duration will be administered over a four 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. 20 treatment sessions are given over a four 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. Diagnosis of Alzheimer's dementia meeting the DSM-IV TR criteria,&#xD;
&#xD;
          3. Apathy Evaluation Scale-Clinician (AES-C) score of ≥ 30,&#xD;
&#xD;
          4. Mini Mental Status Examination (MMSE) ≥ 18,&#xD;
&#xD;
          5. Subjects who clear the TMS adult safety scale (TASS)&#xD;
&#xD;
          6. On stable dose of antidepressants or dementia medicines (if applicable) for at least&#xD;
             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>
  <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>August 2019</verification_date>
  <study_first_submitted>July 11, 2014</study_first_submitted>
  <study_first_submitted_qc>July 11, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 15, 2014</study_first_posted>
  <last_update_submitted>August 20, 2019</last_update_submitted>
  <last_update_submitted_qc>August 20, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 21, 2019</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>apathy</keyword>
  <keyword>Alzheimer's</keyword>
  <keyword>executive function</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dementia</mesh_term>
    <mesh_term>Alzheimer Disease</mesh_term>
  </condition_browse>
  <!-- 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/NCT02190084
org study id: 547461
nct id: NCT02190084
lead sponsor: 
has dmc: No
Alzheimer's Dementia (AD) is a major public health problem. Apathy, a profound loss of
      motivation, is seen in majority of patients with AD. Dysfunction of the front of the brain
      and loss of dopamine, a type of neurochemical, in this part of brain results in apathy.
      Presence of apathy is linked to deficits in planning sequential tasks such as keeping a
      routine. Patients with apathy have poor physical function and their caregivers experience
      extra burden. Unfortunately there are no good medications to treat apathy. FDA has approved
      the use of brain stimulation by a magnet known as repetitive transcranial magnetic
      stimulation (rTMS), for treatment of depression. rTMS increases dopamine when applied to
      frontal lobe of brain so we propose that rTMS would be a good treatment option for apathy in
      AD. Study hypotheses include that rTMS to the dorsolateral prefrontal cortex (DLPFC) will
      improve apathy and executive function better than sham treatment in those with AD.
Objective: Alzheimer's Dementia (AD) is a major public health problem. Apathy, a profound
      loss of motivation, is seen in majority of patients with AD. Dysfunction of the front of the
      brain and loss of dopamine, a type of neurochemical, in this part of brain results in apathy.
      Presence of apathy is linked to deficits in planning sequential tasks such as keeping a
      routine. Patients with apathy have poor physical function and their caregivers experience
      extra burden. Unfortunately there are no good medications to treat apathy. FDA has approved
      the use of brain stimulation by a magnet known as repetitive transcranial magnetic
      stimulation (rTMS), for treatment of depression. rTMS increases dopamine when applied to
      frontal lobe of brain so we propose that rTMS would be a good treatment option for apathy in
      AD.

      Specific Aims: To determine the efficacy of rTMS to the dorsolateral prefrontal cortex
      (DLPFC) in treating apathy in mild AD in comparison to sham treatment.

      • To compare the efficacy of rTMS to the DLPFC on executive function in mild AD in comparison
      to sham treatment.

      Research Plan: Current study is a prospective randomized sham controlled study of daily rTMS.

      Methods: Up to 500 subjects will be pre-screened to enroll 100 subjects for screening and
      randomizing up to 50 subjects to analyze 20 completers. Subjects with mild AD and apathy will
      be randomly assigned to rTMS or sham treatment after consent. All subjects will be tested for
      memory, behavioral problems, functioning and caregiver burden. Apathy will be assessed using
      the Apathy Evaluation Scale. Memory, executive function, functional status and caregiver
      burden will be assessed. Subjects will receive daily treatments for 4 weeks with either rTMS
      or sham coil for a total of 20 treatments. Neither the subject nor the investigators will
      know which treatment the subject is receiving. Testing will be repeated at the end of 4 weeks
      and at 8 and 12 weeks after treatment.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Apathy Evaluation Scale (AES)
time frame: 4 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: 4 weeks
description: Widely used test for assessment of executive function.
measure: Exit 25
time frame: 4 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. 20 treatment sessions are given over a four week period.
arm group label: Sham coil treatment
arm group type: Sham Comparator
description: Neurostar repetitive transcranial magnetic stimulator. 20 treatments identical in duration will be administered over a four 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. 20 treatment sessions are given over a four 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
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: Dementia
mesh term: Alzheimer Disease