<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/NCT03256643</url>
  </required_header>
  <id_info>
    <org_study_id>123</org_study_id>
    <nct_id>NCT03256643</nct_id>
  </id_info>
  <brief_title>Brain Injury Therapy of Exercise and Enriched Environment</brief_title>
  <acronym>BITEEE</acronym>
  <official_title>Cognitive and Physical Effects of Exercise or Exercise With Enrichment on People With TBI</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Wayne State University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Wayne State University</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine whether exercise or exercise with enrichment is&#xD;
      beneficial in individuals who previously had a head injury. The enrichment will consist of a&#xD;
      cultural educational program that will include ethnic food, music, slides and a talk. A&#xD;
      series of tests that measure mental function and balance will be done before and after the&#xD;
      exercise or the exercise/enrichment program will be done to measure efficacy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Traumatic brain injury (TBI) results in long-lasting physical and cognitive deficits. The&#xD;
      purpose of this study is to determine whether exercise or exercise with enrichment is&#xD;
      beneficial in individuals who previously had a head injury. The environmental enrichment will&#xD;
      consist of a cultural educational program that will include ethnic food, music, slides and a&#xD;
      talk on 8 different cultures. Individuals will be evaluated using neuropsychological and&#xD;
      physical tests before and after the intervention. Testing will consist of Repeatable Battery&#xD;
      for the Assessment of Neuropsychological Status (RBANS), Trailmaking Test (TMT), Immediate&#xD;
      Post-Concussion Assessment and Cognitive Testing (ImPACT), Quality of Life in Brain Injury&#xD;
      Questionnaire (QOLIBRI), 10 meter walk, and the NIH Toolbox Standing Balance Test. Initial&#xD;
      testing will include the Disability Rating Scale to help balance groups (after random&#xD;
      assignment) in terms of baseline ability.&#xD;
&#xD;
      In rodents, exercise or an enriched environment after TBI improve cognitive function and&#xD;
      motor function and the combination results in even greater improvement. The mechanism of&#xD;
      cognitive improvement from exercise or environmental enrichment relates to increases in brain&#xD;
      derived neurotrophic factor and neurogenesis in the hippocampus. An additional possible&#xD;
      mechanism of the positive effects of exercise or enrichment is a reduction in inflammation.&#xD;
      Our hypothesis is that exercise or exercise with enrichment will result in better motor&#xD;
      performance and improved cognitive ability.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">May 1, 2016</start_date>
  <completion_date type="Anticipated">December 1, 2020</completion_date>
  <primary_completion_date type="Actual">July 1, 2018</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Trail Making Part B</measure>
    <time_frame>Change from Baseline at 9 weeks.</time_frame>
    <description>Trail Making test is a measure of visual conceptual and visuomotor tracking, attention, and maintenance of cognitive set-shifting that is known to be highly sensitive to brain damage.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Quality of Life in Brain Injury Questionnaire</measure>
    <time_frame>Change from Baseline at 9 weeks.</time_frame>
    <description>Quality of Life in Brain Injury Questionnaire is a thirty-seven question self-reported measure of overall patient health.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT)</measure>
    <time_frame>Change from Baseline at 9 weeks.</time_frame>
    <description>ImPACT is a measure which consists of a word discrimination, design memory, X/O, symbol matching, color matching, and three letter memory tasks.</description>
  </other_outcome>
  <other_outcome>
    <measure>Ten Minute Walk</measure>
    <time_frame>Change from Baseline at 9 weeks.</time_frame>
    <description>Ten Meter Walk is a physical measure of balance and gait, consisting of measuring the time it takes for participants to walk.</description>
  </other_outcome>
  <other_outcome>
    <measure>NIH Toolbox Standing Balance Test</measure>
    <time_frame>Change from Baseline and at 9 weeks.</time_frame>
    <description>Standing Balance Test measures the detection of spatial orientation, maintenance of posture in static and dynamic conditions.</description>
  </other_outcome>
  <other_outcome>
    <measure>Repeatable Battery for the Assessment of Neuropsychological Status</measure>
    <time_frame>Change from Baseline at 9 weeks.</time_frame>
    <description>is a measure of immediate memory, visuospatial/constructional skills, language, attention, and delayed memory.</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">42</enrollment>
  <condition>Brain Injuries</condition>
  <arm_group>
    <arm_group_label>Exercise</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Exercise is the intervention. People be tested before the start of, and after the end of the eight (8) week exercise program.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Delayed Exercise</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Delayed Exercise Group will have exercise as intervention. People be tested before the start of, and after the end of the eight (8) weeks then after exercise intervention.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Exercise and Enrichment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Exercise and Enrichment Group is the intervention. The group will be tested at the beginning and end of their exercise/enrichment program.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Exercise</intervention_name>
    <description>Exercise intervention will consist of 8 exercise classes and exercises at home. A booklet will be given to each person that has a description and photograph of each exercise that designed to work on core strength and balance.</description>
    <arm_group_label>Exercise</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Delayed Exercise</intervention_name>
    <description>People will be tested up to 40 weeks after beginning the intervention.</description>
    <arm_group_label>Delayed Exercise</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Exercise and enrichment</intervention_name>
    <description>Exercise and enrichment will consist of the same exercise program described for the exercise intervention. The enrichment protocol consisting of cultural educational program will take place during the exercises and breaks for this group.</description>
    <arm_group_label>Exercise and Enrichment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Traumatic brain injury (TBI) person&#xD;
&#xD;
          -  1 to 15 year post-TBI&#xD;
&#xD;
          -  Initial Glascow Coma SCale (GCS) of &lt; or = 12&#xD;
&#xD;
          -  18-75 years old&#xD;
&#xD;
          -  able to perform standardized exercise program&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          -  Inability to walk independently without assistive aids.&#xD;
&#xD;
          -  Severe cardiovascular limitations limiting exercise of up to 5 metabolic equivalents.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jean Peduzzi-Nelson, Ph.D.</last_name>
    <role>Study Director</role>
    <affiliation>Wayne State University I</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Oakwood Heritage</name>
      <address>
        <city>Taylor</city>
        <state>Michigan</state>
        <zip>48180</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Alwis DS, Rajan R. Environmental enrichment and the sensory brain: the role of enrichment in remediating brain injury. Front Syst Neurosci. 2014 Sep 2;8:156. doi: 10.3389/fnsys.2014.00156. eCollection 2014.</citation>
    <PMID>25228861</PMID>
  </reference>
  <reference>
    <citation>Bondi CO, Klitsch KC, Leary JB, Kline AE. Environmental enrichment as a viable neurorehabilitation strategy for experimental traumatic brain injury. J Neurotrauma. 2014 May 15;31(10):873-88. doi: 10.1089/neu.2014.3328. Epub 2014 Apr 17.</citation>
    <PMID>24555571</PMID>
  </reference>
  <reference>
    <citation>Fischer FR, Peduzzi JD. Functional recovery in rats with chronic spinal cord injuries after exposure to an enriched environment. J Spinal Cord Med. 2007;30(2):147-55. doi: 10.1080/10790268.2007.11753926.</citation>
    <PMID>17591227</PMID>
  </reference>
  <reference>
    <citation>Gomez-Pinilla F, Hillman C. The influence of exercise on cognitive abilities. Compr Physiol. 2013 Jan;3(1):403-28. doi: 10.1002/cphy.c110063.</citation>
    <PMID>23720292</PMID>
  </reference>
  <reference>
    <citation>Piao CS, Stoica BA, Wu J, Sabirzhanov B, Zhao Z, Cabatbat R, Loane DJ, Faden AI. Late exercise reduces neuroinflammation and cognitive dysfunction after traumatic brain injury. Neurobiol Dis. 2013 Jun;54:252-63. doi: 10.1016/j.nbd.2012.12.017. Epub 2013 Jan 8.</citation>
    <PMID>23313314</PMID>
  </reference>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>December 9, 2014</study_first_submitted>
  <study_first_submitted_qc>August 19, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 22, 2017</study_first_posted>
  <last_update_submitted>March 25, 2020</last_update_submitted>
  <last_update_submitted_qc>March 25, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 26, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Wayne State University</investigator_affiliation>
    <investigator_full_name>Jay M Meythaler</investigator_full_name>
    <investigator_title>Professor of Medicine with Tenure</investigator_title>
  </responsible_party>
  <keyword>traumatic brain injury</keyword>
  <keyword>brain contusion</keyword>
  <keyword>craniocerebral trauma</keyword>
  <keyword>exercise therapy</keyword>
  <keyword>chronic brain injury</keyword>
  <keyword>environment impact</keyword>
  <keyword>cognitive therapy</keyword>
  <keyword>health facility environment</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Brain Injuries</mesh_term>
    <mesh_term>Wounds and Injuries</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/NCT03256643
org study id: 123
nct id: NCT03256643
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to determine whether exercise or exercise with enrichment is
      beneficial in individuals who previously had a head injury. The enrichment will consist of a
      cultural educational program that will include ethnic food, music, slides and a talk. A
      series of tests that measure mental function and balance will be done before and after the
      exercise or the exercise/enrichment program will be done to measure efficacy.
Traumatic brain injury (TBI) results in long-lasting physical and cognitive deficits. The
      purpose of this study is to determine whether exercise or exercise with enrichment is
      beneficial in individuals who previously had a head injury. The environmental enrichment will
      consist of a cultural educational program that will include ethnic food, music, slides and a
      talk on 8 different cultures. Individuals will be evaluated using neuropsychological and
      physical tests before and after the intervention. Testing will consist of Repeatable Battery
      for the Assessment of Neuropsychological Status (RBANS), Trailmaking Test (TMT), Immediate
      Post-Concussion Assessment and Cognitive Testing (ImPACT), Quality of Life in Brain Injury
      Questionnaire (QOLIBRI), 10 meter walk, and the NIH Toolbox Standing Balance Test. Initial
      testing will include the Disability Rating Scale to help balance groups (after random
      assignment) in terms of baseline ability.

      In rodents, exercise or an enriched environment after TBI improve cognitive function and
      motor function and the combination results in even greater improvement. The mechanism of
      cognitive improvement from exercise or environmental enrichment relates to increases in brain
      derived neurotrophic factor and neurogenesis in the hippocampus. An additional possible
      mechanism of the positive effects of exercise or enrichment is a reduction in inflammation.
      Our hypothesis is that exercise or exercise with enrichment will result in better motor
      performance and improved cognitive ability.
allocation: Non-Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Trail Making Part B
time frame: Change from Baseline at 9 weeks.
description: Trail Making test is a measure of visual conceptual and visuomotor tracking, attention, and maintenance of cognitive set-shifting that is known to be highly sensitive to brain damage.
measure: Quality of Life in Brain Injury Questionnaire
time frame: Change from Baseline at 9 weeks.
description: Quality of Life in Brain Injury Questionnaire is a thirty-seven question self-reported measure of overall patient health.
measure: Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT)
time frame: Change from Baseline at 9 weeks.
description: ImPACT is a measure which consists of a word discrimination, design memory, X/O, symbol matching, color matching, and three letter memory tasks.
measure: Ten Minute Walk
time frame: Change from Baseline at 9 weeks.
description: Ten Meter Walk is a physical measure of balance and gait, consisting of measuring the time it takes for participants to walk.
measure: NIH Toolbox Standing Balance Test
time frame: Change from Baseline and at 9 weeks.
description: Standing Balance Test measures the detection of spatial orientation, maintenance of posture in static and dynamic conditions.
measure: Repeatable Battery for the Assessment of Neuropsychological Status
time frame: Change from Baseline at 9 weeks.
description: is a measure of immediate memory, visuospatial/constructional skills, language, attention, and delayed memory.
arm group label: Exercise
arm group type: Experimental
description: Exercise is the intervention. People be tested before the start of, and after the end of the eight (8) week exercise program.
arm group label: Delayed Exercise
arm group type: Experimental
description: Delayed Exercise Group will have exercise as intervention. People be tested before the start of, and after the end of the eight (8) weeks then after exercise intervention.
arm group label: Exercise and Enrichment
arm group type: Experimental
description: Exercise and Enrichment Group is the intervention. The group will be tested at the beginning and end of their exercise/enrichment program.
intervention type: Behavioral
intervention name: Exercise
description: Exercise intervention will consist of 8 exercise classes and exercises at home. A booklet will be given to each person that has a description and photograph of each exercise that designed to work on core strength and balance.
arm group label: Exercise
intervention type: Behavioral
intervention name: Delayed Exercise
description: People will be tested up to 40 weeks after beginning the intervention.
arm group label: Delayed Exercise
intervention type: Behavioral
intervention name: Exercise and enrichment
description: Exercise and enrichment will consist of the same exercise program described for the exercise intervention. The enrichment protocol consisting of cultural educational program will take place during the exercises and breaks for this group.
arm group label: Exercise and Enrichment
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Jean Peduzzi-Nelson, Ph.D.
role: Study Director
affiliation: Wayne State University I
facility: 
country: United States
citation: Alwis DS, Rajan R. Environmental enrichment and the sensory brain: the role of enrichment in remediating brain injury. Front Syst Neurosci. 2014 Sep 2;8:156. doi: 10.3389/fnsys.2014.00156. eCollection 2014.
PMID: 25228861
citation: Bondi CO, Klitsch KC, Leary JB, Kline AE. Environmental enrichment as a viable neurorehabilitation strategy for experimental traumatic brain injury. J Neurotrauma. 2014 May 15;31(10):873-88. doi: 10.1089/neu.2014.3328. Epub 2014 Apr 17.
PMID: 24555571
citation: Fischer FR, Peduzzi JD. Functional recovery in rats with chronic spinal cord injuries after exposure to an enriched environment. J Spinal Cord Med. 2007;30(2):147-55. doi: 10.1080/10790268.2007.11753926.
PMID: 17591227
citation: Gomez-Pinilla F, Hillman C. The influence of exercise on cognitive abilities. Compr Physiol. 2013 Jan;3(1):403-28. doi: 10.1002/cphy.c110063.
PMID: 23720292
citation: Piao CS, Stoica BA, Wu J, Sabirzhanov B, Zhao Z, Cabatbat R, Loane DJ, Faden AI. Late exercise reduces neuroinflammation and cognitive dysfunction after traumatic brain injury. Neurobiol Dis. 2013 Jun;54:252-63. doi: 10.1016/j.nbd.2012.12.017. Epub 2013 Jan 8.
PMID: 23313314
responsible party type: Principal Investigator
investigator affiliation: Wayne State University
investigator full name: Jay M Meythaler
investigator title: Professor of Medicine with Tenure
mesh term: Brain Injuries
mesh term: Wounds and Injuries
sharing ipd: No