<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/NCT03790657</url>
  </required_header>
  <id_info>
    <org_study_id>E3115-R</org_study_id>
    <secondary_id>I01RX003115</secondary_id>
    <nct_id>NCT03790657</nct_id>
  </id_info>
  <brief_title>CONTROL Walking Study</brief_title>
  <official_title>Cerebral Networks of Locomotor Learning and Retention in Older Adults</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>VA Office of Research and Development</agency>
      <agency_class>U.S. Fed</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>VA Office of Research and Development</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Older adults often experience substantial deficits in walking ability, especially for walking&#xD;
      tasks that are more complex such as obstacle crossing. This is due in part to changes in the&#xD;
      brain that make performance of physical and cognitive tasks more difficult. Rehabilitation&#xD;
      can help to improve walking ability, but effective rehabilitation is time consuming and&#xD;
      expensive. New approaches are needed to improve the efficiency of rehabilitation so that&#xD;
      gains in walking ability are widely attainable. A promising strategy is to focus on enhancing&#xD;
      motor learning, which is defined as improved ability to perform a motor task due to practice&#xD;
      or experience. The investigators will investigate the use of non-invasive brain stimulation&#xD;
      to increase motor learning and retention of the newly learned walking skills. The&#xD;
      investigators will also use neuroimaging to assess brain characteristics that explain how&#xD;
      motor learning works. The knowledge gained from this study is expected to contribute to&#xD;
      better understanding of mechanistic targets and intervention approaches to improve&#xD;
      rehabilitation of walking.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Aging often leads to substantial declines in walking function, especially for walking tasks&#xD;
      that are more complex such as obstacle crossing. This is due in part to a lack of continued&#xD;
      practice of complex walking (sedentary lifestyle) combined with age-related deficits of brain&#xD;
      structure and the integrity of brain networks. Neurorehabilitation can contribute to recovery&#xD;
      of lost walking function in older adults, but major and persistent improvements are elusive.&#xD;
      A cornerstone of neurorehabilitation is motor learning, defined as an enduring change in the&#xD;
      ability to perform a motor task due to practice or experience. Unfortunately, in most&#xD;
      clinical settings, the time and cost demands of delivering a sufficiently intensive motor&#xD;
      learning intervention is not feasible. There is a need for research to develop strategies for&#xD;
      enhancing motor learning of walking (&quot;locomotor learning&quot;) in order to improve the&#xD;
      effectiveness of neurorehabilitation.&#xD;
&#xD;
      The objective of this study is to use non-invasive brain stimulation to augment locomotor&#xD;
      learning and to investigate brain networks that are responsible for locomotor learning in&#xD;
      mobility-compromised older adults. The investigators have shown that frontal brain regions,&#xD;
      particularly prefrontal cortex, are crucial to control of complex walking tasks. The&#xD;
      investigators' neuroimaging and neuromodulation studies also show that prefrontal cortex&#xD;
      structure and network connectivity are important for acquisition and consolidation of new&#xD;
      motor skills. However, a major gap exists regarding learning of walking tasks. The proposed&#xD;
      study is designed to address this gap. The investigators' pilot data from older adults shows&#xD;
      that prefrontal transcranial direct current stimulation (tDCS) administered during learning&#xD;
      of a complex obstacle walking task contributes to multi-day retention of task performance. In&#xD;
      the proposed study the investigators will build upon this pilot work by conducting a full&#xD;
      scale trial that also investigates mechanisms related to brain structure, functional&#xD;
      activity, and network connectivity. The investigators will address the following specific&#xD;
      aims:&#xD;
&#xD;
      Specific Aim 1: Determine the extent to which prefrontal tDCS augments the effect of task&#xD;
      practice for retention of performance on a complex obstacle walking task.&#xD;
&#xD;
      Specific Aim 2: Determine the extent to which retention of performance is associated with&#xD;
      individual differences in baseline and practice-induced changes in brain measures (including&#xD;
      gray matter volume and brain network segregation).&#xD;
&#xD;
      Specific Aim 3: Investigate the extent to which tDCS modifies resting state network&#xD;
      segregation.&#xD;
&#xD;
      The investigators anticipate that prefrontal tDCS will augment retention of locomotor&#xD;
      learning, and that the data will provide the first evidence of specific brain mechanisms&#xD;
      responsible for locomotor learning/retention in older adults with mobility deficits. This new&#xD;
      knowledge will provide a clinically feasible intervention approach as well as reveal&#xD;
      mechanistic targets for future interventions to enhance locomotor learning and retention.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 1, 2019</start_date>
  <completion_date type="Anticipated">April 30, 2024</completion_date>
  <primary_completion_date type="Anticipated">April 30, 2024</primary_completion_date>
  <phase>Early Phase 1</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>
    <intervention_model_description>Participants will randomized to one of two dosages of transcranial direct current stimulation (tDCS): Dosage A or Dosage B</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
    <masking_description>Participants will not be told which dosage group they are assigned to. Outcomes Assessors will not be told which dosage group the participant was randomized to.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Walking speed change from baseline</measure>
    <time_frame>Measured at follow up visit (approximately three weeks after baseline)</time_frame>
    <description>Change in the fastest safe walking speed over a complex walking course</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Prefrontal cortex gray matter volume change from baseline</measure>
    <time_frame>Measured at follow up visit (approximately three weeks after baseline)</time_frame>
    <description>Change in the volume of gray matter in the prefrontal cortex, as measured by MRI</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Brain resting state network segregation</measure>
    <time_frame>Measured at follow up visit (approximately three weeks after baseline)</time_frame>
    <description>Change in resting state network segregation.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Aging</condition>
  <arm_group>
    <arm_group_label>tDCS Dosage A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>mild electrical stimulation (Dosage level &quot;A&quot;) delivered to the frontal region of the brain during practice of a complex walking task</description>
  </arm_group>
  <arm_group>
    <arm_group_label>tDCS Dosage B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>mild electrical stimulation (Dosage level &quot;B&quot;) delivered to the frontal region of the brain during practice of a complex walking task</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>practice of a complex walking task</intervention_name>
    <description>walking over obstacles</description>
    <arm_group_label>tDCS Dosage A</arm_group_label>
    <arm_group_label>tDCS Dosage B</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Dosage A: transcranial direct current stimulation (tDCS)</intervention_name>
    <description>mild electrical stimulation delivered to the frontal region of the brain</description>
    <arm_group_label>tDCS Dosage A</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Dosage B: transcranial direct current stimulation (tDCS)</intervention_name>
    <description>mild electrical stimulation delivered to the frontal region of the brain</description>
    <arm_group_label>tDCS Dosage B</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  age 65 years or older&#xD;
&#xD;
          -  preferred 10m walking speed &lt; 1.1 m/s&#xD;
&#xD;
          -  self-report of &quot;some difficulty with walking tasks, such as becoming tired when&#xD;
             walking a quarter mile, or when climbing two flights of stairs, or when performing&#xD;
             household chores.&quot;&#xD;
&#xD;
          -  Willingness to be randomized to either study group and to participate in all aspects&#xD;
             of study assessment and intervention&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Diagnosed neurological disorder or injury of the central nervous system, or&#xD;
             observation of symptoms consistent with such a condition (Alzheimer's, Parkinson's,&#xD;
             stroke, etc.)&#xD;
&#xD;
          -  Contraindications to non-invasive brain stimulation (e.g., metal in head, wound on&#xD;
             scalp)&#xD;
&#xD;
          -  Contraindications to magnetic resonance imaging (e.g., metal in body, claustrophobia,&#xD;
             etc).&#xD;
&#xD;
          -  Use of medications affecting the central nervous system&#xD;
&#xD;
          -  severe arthritis, such as awaiting joint replacement&#xD;
&#xD;
          -  severe obesity (body mass index &gt; 35)&#xD;
&#xD;
          -  current cardiovascular, lung or renal disease; diabetes; terminal illness&#xD;
&#xD;
          -  myocardial infarction or major heart surgery in the previous year&#xD;
&#xD;
          -  cancer treatment in the past year, except for nonmelanoma skin cancers and cancers&#xD;
             having an excellent prognosis (e.g., early stage breast or prostate cancer)&#xD;
&#xD;
          -  current diagnosis of schizophrenia, other psychotic disorders, or bipolar disorder&#xD;
&#xD;
          -  uncontrolled hypertension at rest (systolic &gt; 180 mmHg and/or diastolic &gt; 100 mmHg)&#xD;
&#xD;
          -  bone fracture or joint replacement in the previous six months&#xD;
&#xD;
          -  current participation in physical therapy for lower extremity function or&#xD;
             cardiopulmonary rehabilitation&#xD;
&#xD;
          -  current enrollment in any clinical trial&#xD;
&#xD;
          -  difficulty communicating with study personnel, and/or non-English speaking&#xD;
&#xD;
          -  planning to relocate out of the area during the study period&#xD;
&#xD;
          -  clinical judgment of investigative team regarding safety or non-compliance&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>65 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>David J. Clark, DSc</last_name>
    <role>Principal Investigator</role>
    <affiliation>North Florida/South Georgia Veterans Health System, Gainesville, FL</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>David J Clark, DSc</last_name>
    <phone>(352) 376-1611</phone>
    <phone_ext>5244</phone_ext>
    <email>David.Clark1@va.gov</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Dorian K Rose, PhD MS BS</last_name>
    <phone>(352) 273-8307</phone>
    <email>Dorian.Rose@va.gov</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>North Florida/South Georgia Veterans Health System, Gainesville, FL</name>
      <address>
        <city>Gainesville</city>
        <state>Florida</state>
        <zip>32608-1135</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Margaret H McCallum</last_name>
      <phone>352-376-1611</phone>
      <phone_ext>5223</phone_ext>
      <email>Margaret.McCallum@va.gov</email>
    </contact>
    <contact_backup>
      <last_name>Heidi Parrish</last_name>
      <phone>(352) 376-1611</phone>
      <phone_ext>105246</phone_ext>
      <email>heidi.parrish@va.gov</email>
    </contact_backup>
    <investigator>
      <last_name>David J. Clark, DSc</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>December 28, 2018</study_first_submitted>
  <study_first_submitted_qc>December 28, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 31, 2018</study_first_posted>
  <last_update_submitted>May 10, 2023</last_update_submitted>
  <last_update_submitted_qc>May 10, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 11, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>aging</keyword>
  <keyword>walking</keyword>
  <keyword>brain</keyword>
  <keyword>electrical stimulation</keyword>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>A Limited Dataset will be created and shared pursuant to a Data Use Agreement appropriately limiting use of the dataset and prohibiting the recipient from identifying or re-identifying (or taking steps to identify or re-identify) any individual whose data are included in the dataset.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>The Limited Dataset will be completed after the study is completed and primary/secondary data accepted for publication.</ipd_time_frame>
  </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/NCT03790657
org study id: E3115-R
secondary id: I01RX003115
nct id: NCT03790657
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
Older adults often experience substantial deficits in walking ability, especially for walking
      tasks that are more complex such as obstacle crossing. This is due in part to changes in the
      brain that make performance of physical and cognitive tasks more difficult. Rehabilitation
      can help to improve walking ability, but effective rehabilitation is time consuming and
      expensive. New approaches are needed to improve the efficiency of rehabilitation so that
      gains in walking ability are widely attainable. A promising strategy is to focus on enhancing
      motor learning, which is defined as improved ability to perform a motor task due to practice
      or experience. The investigators will investigate the use of non-invasive brain stimulation
      to increase motor learning and retention of the newly learned walking skills. The
      investigators will also use neuroimaging to assess brain characteristics that explain how
      motor learning works. The knowledge gained from this study is expected to contribute to
      better understanding of mechanistic targets and intervention approaches to improve
      rehabilitation of walking.
Aging often leads to substantial declines in walking function, especially for walking tasks
      that are more complex such as obstacle crossing. This is due in part to a lack of continued
      practice of complex walking (sedentary lifestyle) combined with age-related deficits of brain
      structure and the integrity of brain networks. Neurorehabilitation can contribute to recovery
      of lost walking function in older adults, but major and persistent improvements are elusive.
      A cornerstone of neurorehabilitation is motor learning, defined as an enduring change in the
      ability to perform a motor task due to practice or experience. Unfortunately, in most
      clinical settings, the time and cost demands of delivering a sufficiently intensive motor
      learning intervention is not feasible. There is a need for research to develop strategies for
      enhancing motor learning of walking ("locomotor learning") in order to improve the
      effectiveness of neurorehabilitation.

      The objective of this study is to use non-invasive brain stimulation to augment locomotor
      learning and to investigate brain networks that are responsible for locomotor learning in
      mobility-compromised older adults. The investigators have shown that frontal brain regions,
      particularly prefrontal cortex, are crucial to control of complex walking tasks. The
      investigators' neuroimaging and neuromodulation studies also show that prefrontal cortex
      structure and network connectivity are important for acquisition and consolidation of new
      motor skills. However, a major gap exists regarding learning of walking tasks. The proposed
      study is designed to address this gap. The investigators' pilot data from older adults shows
      that prefrontal transcranial direct current stimulation (tDCS) administered during learning
      of a complex obstacle walking task contributes to multi-day retention of task performance. In
      the proposed study the investigators will build upon this pilot work by conducting a full
      scale trial that also investigates mechanisms related to brain structure, functional
      activity, and network connectivity. The investigators will address the following specific
      aims:

      Specific Aim 1: Determine the extent to which prefrontal tDCS augments the effect of task
      practice for retention of performance on a complex obstacle walking task.

      Specific Aim 2: Determine the extent to which retention of performance is associated with
      individual differences in baseline and practice-induced changes in brain measures (including
      gray matter volume and brain network segregation).

      Specific Aim 3: Investigate the extent to which tDCS modifies resting state network
      segregation.

      The investigators anticipate that prefrontal tDCS will augment retention of locomotor
      learning, and that the data will provide the first evidence of specific brain mechanisms
      responsible for locomotor learning/retention in older adults with mobility deficits. This new
      knowledge will provide a clinically feasible intervention approach as well as reveal
      mechanistic targets for future interventions to enhance locomotor learning and retention.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Participants will randomized to one of two dosages of transcranial direct current stimulation (tDCS): Dosage A or Dosage B
primary purpose: Basic Science
masking: Double (Participant, Outcomes Assessor)
masking description: Participants will not be told which dosage group they are assigned to. Outcomes Assessors will not be told which dosage group the participant was randomized to.
measure: Walking speed change from baseline
time frame: Measured at follow up visit (approximately three weeks after baseline)
description: Change in the fastest safe walking speed over a complex walking course
measure: Prefrontal cortex gray matter volume change from baseline
time frame: Measured at follow up visit (approximately three weeks after baseline)
description: Change in the volume of gray matter in the prefrontal cortex, as measured by MRI
measure: Brain resting state network segregation
time frame: Measured at follow up visit (approximately three weeks after baseline)
description: Change in resting state network segregation.
arm group label: tDCS Dosage A
arm group type: Experimental
description: mild electrical stimulation (Dosage level "A") delivered to the frontal region of the brain during practice of a complex walking task
arm group label: tDCS Dosage B
arm group type: Experimental
description: mild electrical stimulation (Dosage level "B") delivered to the frontal region of the brain during practice of a complex walking task
intervention type: Behavioral
intervention name: practice of a complex walking task
description: walking over obstacles
arm group label: tDCS Dosage A
arm group label: tDCS Dosage B
intervention type: Device
intervention name: Dosage A: transcranial direct current stimulation (tDCS)
description: mild electrical stimulation delivered to the frontal region of the brain
arm group label: tDCS Dosage A
intervention type: Device
intervention name: Dosage B: transcranial direct current stimulation (tDCS)
description: mild electrical stimulation delivered to the frontal region of the brain
arm group label: tDCS Dosage B
criteria: 
gender: All
minimum age: 65 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: David J. Clark, DSc
role: Principal Investigator
affiliation: North Florida/South Georgia Veterans Health System, Gainesville, FL
last name: David J Clark, DSc
phone: (352) 376-1611
phone ext: 5244
email: David.Clark1@va.gov
last name: Dorian K Rose, PhD MS BS
phone: (352) 273-8307
email: Dorian.Rose@va.gov
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: United States
responsible party type: Sponsor
sharing ipd: Yes
ipd description: A Limited Dataset will be created and shared pursuant to a Data Use Agreement appropriately limiting use of the dataset and prohibiting the recipient from identifying or re-identifying (or taking steps to identify or re-identify) any individual whose data are included in the dataset.
ipd info type: Study Protocol
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd time frame: The Limited Dataset will be completed after the study is completed and primary/secondary data accepted for publication.