<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/NCT03765398</url>
  </required_header>
  <id_info>
    <org_study_id>2018-1257</org_study_id>
    <secondary_id>2P30AG022849-11</secondary_id>
    <nct_id>NCT03765398</nct_id>
  </id_info>
  <brief_title>VR-CogMoBal Training for Reducing Falls Among Older Adults With Mild Cognitive Impairment</brief_title>
  <official_title>Virtual-reality Based Cognitive-motor-balance (VR-CogMoBal) Training: Examining Behavioral and Neuromarkers for Fall-risk Reduction in Older Adults With Mild Cognitive Impairment</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Illinois at Chicago</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute on Aging (NIA)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Illinois at Chicago</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>
      Older adults often display gait instability, impaired balance control and cognitive decline&#xD;
      that lead to falls and fall risks. Approximately 60% of the elderly people with cognitive&#xD;
      deficits experience a detrimental fall each year. Such motor and cognitive impairments&#xD;
      further decreases physical activity levels in this population leading to restricted community&#xD;
      integration, social behavior, depression and long-term disability. With the help of computer&#xD;
      technology, studies have employed virtual-reality based interventions to address the&#xD;
      above-mentioned concerns including sensori-motor, balance control and cognitive impairments.&#xD;
      Previous studies have demonstrated promising results on improving the behavioral outcomes,&#xD;
      and have identified such interventions have the potential to improve the underlying&#xD;
      neurophysiological outcomes as well. While VR based training studies have demonstrated&#xD;
      remarkable improvement in the balance control and gait parameters, physical activity levels&#xD;
      and fall risk reduction, the gains on cognitive function is less pronounced. There is little&#xD;
      evidence that VR-based training can explicitly address the higher executive cognitive domains&#xD;
      associated with balance control and falls. Further, the effect of VR-based training on&#xD;
      balance control and cognitive function is unknown among the older adults with mild cognitive&#xD;
      impairment. Therefore, to address the cognitive domains explicitly, the current study aims to&#xD;
      test the applicability of Wii-Fit Nintendo along with an additional cognitive load delivered&#xD;
      via VR-based cognitive-motor training paradigm (VR-CogMoBal) in older adults with mild&#xD;
      cognitive impairment. Lastly, the study also aims to identify the effect of such training on&#xD;
      the underlying behavioral and neural outcomes. The behavioral outcomes will be assessed via&#xD;
      performance on dual-tasking and clinical measures in the laboratory. The underlying neural&#xD;
      outcomes will be assessed via fMRI outcomes. In order to determine the generalizing training&#xD;
      effect at community level, a pilot sub-study to determine the physical activity levels post 4&#xD;
      weeks of training will also be conducted.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Older adults suffer from mild cognitive impairments with a prevalence rate of 3% to 22% and&#xD;
      an incidence rate of 1% to 6% per year in the United States. Along with age associated&#xD;
      locomotor-balance impairments, such cognitive decline among the elderly is known to increase&#xD;
      the risk of falls, reduced physical activity and community integration, thus contributing to&#xD;
      long-term disability. Daily living activities comprises of several concurrent motor and&#xD;
      cognitive performances (dual-tasking) such as shopping in a supermarket, that requires higher&#xD;
      executive cognitive functions and intact locomotor-balance control abilities. Falls during&#xD;
      dual-tasking occur mostly due to the interference caused, i.e. during dual-task performances,&#xD;
      either one or both task (motor or cognitive) performance is deteriorated that is known as&#xD;
      cognitive-motor interference. Given that dual-task performances decline due to age-associated&#xD;
      factors, daily living activities are highly challenging and difficult to perform for older&#xD;
      adults with mild cognitive impairment. Although there are several conventional methods that&#xD;
      incorporate locomotor-balance training, the nature of such interventions does not result in&#xD;
      pronounced cognitive gains. Additionally, these interventions lack multi-sensory feedback,&#xD;
      and due to the monotonous and repeated task practice of exercises characteristic, individuals&#xD;
      do not seem to adhere to therapy leading to less compliance and decreased motivation to&#xD;
      exercise training. In order to overcome such barriers, alternate form of therapy with the&#xD;
      help of Virtual-reality devices, especially off the shelf commercially available exercise&#xD;
      platforms emerged for training purposes. Although there is evidence that VR based training&#xD;
      improves locomotor-balance control and is known to implicitly address cognitive functions,&#xD;
      there is no knowledge that such VR based training can explicitly address higher executive&#xD;
      cognitive functions. Therefore, based on preliminary studies tested the efficacy of cognitive&#xD;
      training along with exergaming delivered via the commercially available off the shelf device-&#xD;
      Wii-fit Nintendo and demonstrated promising results in improving balance control and&#xD;
      cognitive function among the individuals with Chronic Stroke. The study resulted in decreased&#xD;
      cognitive-motor interference during dual-task performance thereby exhibiting an improved&#xD;
      performance on both cognitive and balance control function. Currently, there is lack of&#xD;
      knowledge in determining specific interventions for improving dual-task performances among&#xD;
      the older adults with MCI. Given that mild cognitive impaired older adults suffer from both&#xD;
      motor and cognitive impairments, there is a need for testing the feasibility of a similar&#xD;
      intervention among them and determine the change in the underlying neural biomarkers.&#xD;
&#xD;
      Aim 1: The study is designed to test the feasibility (tolerability, compliance and&#xD;
      effectiveness) of VR-CogMoBal training to improve physical function and reduce fall-risk in&#xD;
      community-dwelling older adults with mild cognitive deficits by lowering cognitive-motor&#xD;
      interference and dual task costs.&#xD;
&#xD;
      Hypothesis: Participants will tolerate the training paradigm and will demonstrate significant&#xD;
      improvements in balance, gait, cardiovascular and cognitive performance under dual-task&#xD;
      conditions.&#xD;
&#xD;
      Aim 2: To examine if the (VR-CogMoBal) will lead to higher cognitive function&#xD;
      post-intervention.&#xD;
&#xD;
      Hypothesis: Post-training compared to pre-training participants will show significantly&#xD;
      greater global cognitive function, executive and working memory and decreased cognitive-motor&#xD;
      load.&#xD;
&#xD;
      Aim 3: To examine effect of VR-CogMoBal Training on changes in structural and functional&#xD;
      connectivity within the cognitive-motor areas in the brain.&#xD;
&#xD;
      Hypothesis: Post-training compared to pre-training, participants will show increased&#xD;
      structural and functional connectivity at rest in the default mode network (memory&#xD;
      consolidation, self-referential memory), fronto-parietal and supplementary motor areas (motor&#xD;
      planning and execution, attention).&#xD;
&#xD;
      Pilot Sub-study aim:&#xD;
&#xD;
      The study aims to monitor the change in the number of steps taken a day before undergoing VR&#xD;
      training and 4 weeks post-training.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">November 28, 2018</start_date>
  <completion_date type="Anticipated">December 16, 2022</completion_date>
  <primary_completion_date type="Anticipated">December 16, 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Movement velocity</measure>
    <time_frame>Baseline (Week 0) and Immediate Post-training (Week 5)</time_frame>
    <description>It is the average speed of center of gravity movement during intentional movement measured in degrees per second under single and dual-task conditions. Higher values indicate better performance.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in end point excursion</measure>
    <time_frame>Baseline (Week 0) and Immediate Post-training (Week 5)</time_frame>
    <description>It is the magnitude of a self-initiated movement (i.e., how far he/she wills to reach a target) without taking a step or losing balance measured in percentage under single and dual-task conditions. Higher values indicate better performance.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in maximum excursion</measure>
    <time_frame>Baseline (Week 0) and Immediate Post-training (Week 5)</time_frame>
    <description>It is the actual magnitude of a self-initiated movement (i.e., how far did he/she actually reach a target) without taking a step or losing balance measured in percentage under single and dual-task conditions. Higher values indicate better performance.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in directional control</measure>
    <time_frame>Baseline (Week 0) and Immediate Post-training (Week 5)</time_frame>
    <description>It is the quality of a self-initiated movement (i.e., amount of movement actually exhibited towards the target to the amount of extraneous movement away from the target) measured in percentage under single and dual-task conditions. Higher values indicate better performance.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in postural stability during reactive balance control (single and dual-task)</measure>
    <time_frame>Baseline (Week 0) and Immediate Post-training (Week 5)</time_frame>
    <description>Reactive balance control will be examined via the stance perturbation test under single and dual-task conditions (simultaneous performance of Letter number sequencing task or auditory stroop task). Postural stability can be defined as simultaneous control of center of mass (COM) position and velocity during slip-like or trip like perturbation relative to the rear edge of base of support (rear heel). The position is normalized with the individual's foot length, and velocity by square root of gravitational acceleration and individual's body height. Larger values indicate greater stability.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in 4 meter walk test</measure>
    <time_frame>Baseline (Week 0) and Immediate Post-training (Week 5)</time_frame>
    <description>The total time taken to complete the 4 meters will be noted. Speed will then be determined by using the formula distance (4 meters) covered by time taken to complete the test. Higher speed indicate better performance.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in gait parameters</measure>
    <time_frame>Baseline (Week 0) and Immediate Post-training (Week 5)</time_frame>
    <description>Spatial and temporal gait parameters like Step length, cadence and stride length will be determined during single and dual-task walking performance via the GaitRite mat. Higher values for step length and stride length, and lower cadence indicates better performance.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change of accuracy in letter number sequencing</measure>
    <time_frame>Baseline (Week 0) and Immediate Post-training (Week 5)</time_frame>
    <description>This is an oral trail making test which includes listing alternate letter and number from the cue given in sequence. This test will be performed under single and dual-task conditions.&#xD;
Accuracy (number of correct responses out of the total responses) of letter number sequencing will be calculated. Higher accuracy indicates better performance.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in accuracy of Auditory stroop</measure>
    <time_frame>Baseline (Week 0) and Immediate Post-training (Week 5)</time_frame>
    <description>This test involves responding to the pitch (high or low) of the words &quot;High&quot; or &quot;Low&quot;. This test will be performed under single and dual-task conditions.&#xD;
Accuracy (number of correct responses out of the total responses) of Auditory stroop will be calculated. Higher accuracy indicates better performance. Higher values indicate better performance.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in dual-task cost</measure>
    <time_frame>Baseline (Week 0) and Immediate Post-training (Week 5)</time_frame>
    <description>Dual-task motor and cognitive cost will be calculated using the formula- [(Dual-task performance- Single Task performance)/Single task performance]. This will be calculated for dual-task performance during intentional postural sway, reactive balance control and gait conditions. Lower cost indicates better performance.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Interference in the reaction time</measure>
    <time_frame>Baseline (Week 0) and Immediate Post-training (Week 5)</time_frame>
    <description>Interference in the reaction time via visual stroop task where the individual is expected to respond to the color in which the word is printed and not read the word. Performance will be identified via time taken to complete the test. Lower time indicate better performance.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in language fluency</measure>
    <time_frame>Baseline (Week 0) and Immediate Post-training (Week 5)</time_frame>
    <description>Language fluency via verbal and category task will be administered. Performance will be identified via the total number of appropriate words responded on each of the task. Higher values indicate better performance.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in reaction time</measure>
    <time_frame>Baseline (Week 0) and Immediate Post-training (Week 5)</time_frame>
    <description>The individual is asked to hit a key on the number keypad when a cue appears on the screen. Performance will be identified with time taken to hit the key after the individual sees the cue in seconds. Lower time indicate better performance.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in paired associated learning</measure>
    <time_frame>Baseline (Week 0) and Immediate Post-training (Week 5)</time_frame>
    <description>Paired associated learning via grid task will be administered. Accuracy (number of correct responses out of the total responses) will be represented in percentage. Higher value indicate better performance.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in spatial working memory</measure>
    <time_frame>Baseline (Week 0) and Immediate Post-training (Week 5)</time_frame>
    <description>Spatial working memory via unveil the star task will be administered. Performance will be identified via the total time (in seconds) to complete the task. Lower time indicate better performance.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in working memory</measure>
    <time_frame>Baseline (Week 0) and Immediate Post-training (Week 5)</time_frame>
    <description>List Sorting Memory test to evaluate working memory. This test requires the participant to recall and sequentially list the visually and orally presented stimuli. The accuracy of the participants response is computer generated. Higher value indicate better performance.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in episodic memory</measure>
    <time_frame>Baseline (Week 0) and Immediate Post-training (Week 5)</time_frame>
    <description>Picture sequence memory test will assess episodic memory of the individual. The number of adjacent pairs of pictures placed correctly will score a point. The scores are computer generated. Higher value indicate better performance.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in accuracy of flanker inhibitory control and attention test</measure>
    <time_frame>Baseline (Week 0) and Immediate Post-training (Week 5)</time_frame>
    <description>Flanker inhibitory control and attention test is used to evaluate the participants ability to inhibit the attention to the stimulus flanking it and focus on a particular stimulus. Accuracy of the responses are recorded and the scores are computer generated. Higher value indicate better performance.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in cognitive flexibility and attention</measure>
    <time_frame>Baseline (Week 0) and Immediate Post-training (Week 5)</time_frame>
    <description>Dimensional Change card sort assesses cognitive flexibility and attention. Participants are asked to match a series of bivalent pictures either by colors or shapes accordingly. Responses are computer recorded and accuracy scores are computer generated. Higher value indicate better performance.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in processing speed</measure>
    <time_frame>Baseline (Week 0) and Immediate Post-training (Week 5)</time_frame>
    <description>Pattern comparison processing speed test is used to evaluate the processing speed. The participants are expected to respond whether the two pictures side-by side are same or not the same. Accuracy will be recorded by the computer and scores are computer generated. Higher value indicate better performance.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in fractional anisotropy</measure>
    <time_frame>Baseline (Week 0) and Immediate Post-training (Week 5)</time_frame>
    <description>Image acquisition will be performed in a 3T and 1.5T Magnetic resonance scanner (MR 750, GE healthcare, Milwaukee). Fractional anisotropy (FA) is a scalar value ranging from 0-1 and change from pre- to post-training will compared to determine the structural and functional connectivity. Increase in FA values post-training will indicate positive results of training.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Berg Balance scale</measure>
    <time_frame>Baseline (Week 0) and Immediate Post-training (Week 5)</time_frame>
    <description>Assess static and dynamic balance. This scale consists of the participant transferring from one chair to another, reaching forward, stepping up and down from a stepping stool, standing with eyes closed and open, one leg standing. It is a 14-item scale with each item score ranging from 0-4. Performance on the scale will be calculated on a total of 56. Less than 45 will indicate greater risk of falling.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in physical activity level (Questionnaires)</measure>
    <time_frame>Baseline (Week 0) and Immediate Post-training (Week 5)</time_frame>
    <description>Questionnaires such as Physical Activity Scale for elderly and activity specific balance confidence scale will be self-reported by the participant. Activity specific balance confidence scale consists of 16 items, and each item score ranges from 0-100. The total score with 0 confidence indicates no confidence and 100 with complete confidence.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in physical activity level</measure>
    <time_frame>Baseline (Week 0) and 4 weeks Post-training (Week 9)</time_frame>
    <description>Average number of steps taken a day by the individual prior to and after training</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Mild Cognitive Impairment</condition>
  <arm_group>
    <arm_group_label>VR Cognitive-motor-balance training</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Virtual reality based cognitive-motor balance (VR-CogMoBal) training will be delivered using the commercially available Wii-Fit Nintendo in conjunction with cognitive training. All participants will undergo 12 sessions of training in a tapering manner for four weeks with 90 minutes of training per session, i.e., 5 sessions for the first week, 3 sessions for the second week, and 2 sessions for the third and fourth week. Each session will be divided into 3 sub-sessions, where each sub-session will consist of playing 4 games in conjunction with cognitive task. All the games will be performed using a Wii-Fit balance board in front of a TV screen.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>VR Cognitive-motor-balance training</intervention_name>
    <description>The participant will play four of the six balance board games Table tilt, Tightrope, Soccer, Balance bubble, Light Run and Basic Step (each game is max 1.5 minutes). Each game will be superimposed with any 3 of the 6 cognitive tasks (word list generation consisting of verbal fluency (VF) and category fluency (CF), digit recall (DR), analogies (AN), mental arithmetic (MA), repeated letter (RL). The cognitive tasks will be randomized making sure that all the cognitive tasks are played with all the games. The cognitive and balance board game scores will be noted on the scoring sheet for each session. A total 10 minutes rest interval between every sub-session will be mandatorily provided.</description>
    <arm_group_label>VR Cognitive-motor-balance training</arm_group_label>
    <other_name>VR-CogMoBal</other_name>
    <other_name>Dual-task training</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  MOCA less than 26 out of 30&#xD;
&#xD;
          -  Bone density with a T-score ≥ -2.5&#xD;
&#xD;
          -  Can understand and communicate in English&#xD;
&#xD;
          -  Ability to stand for at least 5 minutes without an assistive device (length of a Wii&#xD;
             Fit game)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  any acute or chronic neurological (Stroke, Parkinson's disease, Alzheimer's disease),&#xD;
             cardiopulmonary, musculoskeletal, or systemic diagnosis&#xD;
&#xD;
          -  recent major surgery (&lt; 6 months) or hospitalization (&lt; 3 months)&#xD;
&#xD;
          -  Use of any sedative drugs&#xD;
&#xD;
          -  HR &gt; 85% of age-predicted maximal heart rate (HRmax) (HRmax = 220 - age)&#xD;
&#xD;
          -  systolic blood pressure (SBP) &gt; 165 mmHg and/or diastolic blood pressure (DBP) &gt; 110&#xD;
             mmHg during resting), and/or oxygen saturation (measured by pulse oximeter) during&#xD;
             resting &lt; 90%&#xD;
&#xD;
          -  Specific to MRI: Self-reported presence of pacemaker, metal implants, and/or&#xD;
             Claustrophobia&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>55 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Tanvi S Bhatt, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Illinois at Chicago</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Lakshmi Kannan, MS PT</last_name>
    <phone>3124133175</phone>
    <email>lkanna2@uic.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>University of Illinois at Chicago</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Tanvi S Bhatt, PhD</last_name>
      <phone>312-355-4443</phone>
      <email>tbhatt6@uic.edu</email>
    </contact>
    <contact_backup>
      <last_name>Lakshmi Kannan, MS</last_name>
      <phone>3124133175</phone>
      <email>lkanna2@uic.edu</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>November 30, 2018</study_first_submitted>
  <study_first_submitted_qc>December 3, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 5, 2018</study_first_posted>
  <last_update_submitted>August 12, 2021</last_update_submitted>
  <last_update_submitted_qc>August 12, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 13, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Illinois at Chicago</investigator_affiliation>
    <investigator_full_name>Tanvi Bhatt</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>Dual-task training</keyword>
  <keyword>Virtual-reality exergaming</keyword>
  <keyword>Cognitive-motor-balance training</keyword>
  <keyword>Mild cognitive impairment</keyword>
  <keyword>Older adults</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cognitive Dysfunction</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/NCT03765398
org study id: 2018-1257
secondary id: 2P30AG022849-11
nct id: NCT03765398
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Older adults often display gait instability, impaired balance control and cognitive decline
      that lead to falls and fall risks. Approximately 60% of the elderly people with cognitive
      deficits experience a detrimental fall each year. Such motor and cognitive impairments
      further decreases physical activity levels in this population leading to restricted community
      integration, social behavior, depression and long-term disability. With the help of computer
      technology, studies have employed virtual-reality based interventions to address the
      above-mentioned concerns including sensori-motor, balance control and cognitive impairments.
      Previous studies have demonstrated promising results on improving the behavioral outcomes,
      and have identified such interventions have the potential to improve the underlying
      neurophysiological outcomes as well. While VR based training studies have demonstrated
      remarkable improvement in the balance control and gait parameters, physical activity levels
      and fall risk reduction, the gains on cognitive function is less pronounced. There is little
      evidence that VR-based training can explicitly address the higher executive cognitive domains
      associated with balance control and falls. Further, the effect of VR-based training on
      balance control and cognitive function is unknown among the older adults with mild cognitive
      impairment. Therefore, to address the cognitive domains explicitly, the current study aims to
      test the applicability of Wii-Fit Nintendo along with an additional cognitive load delivered
      via VR-based cognitive-motor training paradigm (VR-CogMoBal) in older adults with mild
      cognitive impairment. Lastly, the study also aims to identify the effect of such training on
      the underlying behavioral and neural outcomes. The behavioral outcomes will be assessed via
      performance on dual-tasking and clinical measures in the laboratory. The underlying neural
      outcomes will be assessed via fMRI outcomes. In order to determine the generalizing training
      effect at community level, a pilot sub-study to determine the physical activity levels post 4
      weeks of training will also be conducted.
Older adults suffer from mild cognitive impairments with a prevalence rate of 3% to 22% and
      an incidence rate of 1% to 6% per year in the United States. Along with age associated
      locomotor-balance impairments, such cognitive decline among the elderly is known to increase
      the risk of falls, reduced physical activity and community integration, thus contributing to
      long-term disability. Daily living activities comprises of several concurrent motor and
      cognitive performances (dual-tasking) such as shopping in a supermarket, that requires higher
      executive cognitive functions and intact locomotor-balance control abilities. Falls during
      dual-tasking occur mostly due to the interference caused, i.e. during dual-task performances,
      either one or both task (motor or cognitive) performance is deteriorated that is known as
      cognitive-motor interference. Given that dual-task performances decline due to age-associated
      factors, daily living activities are highly challenging and difficult to perform for older
      adults with mild cognitive impairment. Although there are several conventional methods that
      incorporate locomotor-balance training, the nature of such interventions does not result in
      pronounced cognitive gains. Additionally, these interventions lack multi-sensory feedback,
      and due to the monotonous and repeated task practice of exercises characteristic, individuals
      do not seem to adhere to therapy leading to less compliance and decreased motivation to
      exercise training. In order to overcome such barriers, alternate form of therapy with the
      help of Virtual-reality devices, especially off the shelf commercially available exercise
      platforms emerged for training purposes. Although there is evidence that VR based training
      improves locomotor-balance control and is known to implicitly address cognitive functions,
      there is no knowledge that such VR based training can explicitly address higher executive
      cognitive functions. Therefore, based on preliminary studies tested the efficacy of cognitive
      training along with exergaming delivered via the commercially available off the shelf device-
      Wii-fit Nintendo and demonstrated promising results in improving balance control and
      cognitive function among the individuals with Chronic Stroke. The study resulted in decreased
      cognitive-motor interference during dual-task performance thereby exhibiting an improved
      performance on both cognitive and balance control function. Currently, there is lack of
      knowledge in determining specific interventions for improving dual-task performances among
      the older adults with MCI. Given that mild cognitive impaired older adults suffer from both
      motor and cognitive impairments, there is a need for testing the feasibility of a similar
      intervention among them and determine the change in the underlying neural biomarkers.

      Aim 1: The study is designed to test the feasibility (tolerability, compliance and
      effectiveness) of VR-CogMoBal training to improve physical function and reduce fall-risk in
      community-dwelling older adults with mild cognitive deficits by lowering cognitive-motor
      interference and dual task costs.

      Hypothesis: Participants will tolerate the training paradigm and will demonstrate significant
      improvements in balance, gait, cardiovascular and cognitive performance under dual-task
      conditions.

      Aim 2: To examine if the (VR-CogMoBal) will lead to higher cognitive function
      post-intervention.

      Hypothesis: Post-training compared to pre-training participants will show significantly
      greater global cognitive function, executive and working memory and decreased cognitive-motor
      load.

      Aim 3: To examine effect of VR-CogMoBal Training on changes in structural and functional
      connectivity within the cognitive-motor areas in the brain.

      Hypothesis: Post-training compared to pre-training, participants will show increased
      structural and functional connectivity at rest in the default mode network (memory
      consolidation, self-referential memory), fronto-parietal and supplementary motor areas (motor
      planning and execution, attention).

      Pilot Sub-study aim:

      The study aims to monitor the change in the number of steps taken a day before undergoing VR
      training and 4 weeks post-training.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change in Movement velocity
time frame: Baseline (Week 0) and Immediate Post-training (Week 5)
description: It is the average speed of center of gravity movement during intentional movement measured in degrees per second under single and dual-task conditions. Higher values indicate better performance.
measure: Change in end point excursion
time frame: Baseline (Week 0) and Immediate Post-training (Week 5)
description: It is the magnitude of a self-initiated movement (i.e., how far he/she wills to reach a target) without taking a step or losing balance measured in percentage under single and dual-task conditions. Higher values indicate better performance.
measure: Change in maximum excursion
time frame: Baseline (Week 0) and Immediate Post-training (Week 5)
description: It is the actual magnitude of a self-initiated movement (i.e., how far did he/she actually reach a target) without taking a step or losing balance measured in percentage under single and dual-task conditions. Higher values indicate better performance.
measure: Change in directional control
time frame: Baseline (Week 0) and Immediate Post-training (Week 5)
description: It is the quality of a self-initiated movement (i.e., amount of movement actually exhibited towards the target to the amount of extraneous movement away from the target) measured in percentage under single and dual-task conditions. Higher values indicate better performance.
measure: Change in postural stability during reactive balance control (single and dual-task)
time frame: Baseline (Week 0) and Immediate Post-training (Week 5)
description: Reactive balance control will be examined via the stance perturbation test under single and dual-task conditions (simultaneous performance of Letter number sequencing task or auditory stroop task). Postural stability can be defined as simultaneous control of center of mass (COM) position and velocity during slip-like or trip like perturbation relative to the rear edge of base of support (rear heel). The position is normalized with the individual's foot length, and velocity by square root of gravitational acceleration and individual's body height. Larger values indicate greater stability.
measure: Change in 4 meter walk test
time frame: Baseline (Week 0) and Immediate Post-training (Week 5)
description: The total time taken to complete the 4 meters will be noted. Speed will then be determined by using the formula distance (4 meters) covered by time taken to complete the test. Higher speed indicate better performance.
measure: Change in gait parameters
time frame: Baseline (Week 0) and Immediate Post-training (Week 5)
description: Spatial and temporal gait parameters like Step length, cadence and stride length will be determined during single and dual-task walking performance via the GaitRite mat. Higher values for step length and stride length, and lower cadence indicates better performance.
measure: Change of accuracy in letter number sequencing
time frame: Baseline (Week 0) and Immediate Post-training (Week 5)
description: This is an oral trail making test which includes listing alternate letter and number from the cue given in sequence. This test will be performed under single and dual-task conditions.
Accuracy (number of correct responses out of the total responses) of letter number sequencing will be calculated. Higher accuracy indicates better performance.
measure: Change in accuracy of Auditory stroop
time frame: Baseline (Week 0) and Immediate Post-training (Week 5)
description: This test involves responding to the pitch (high or low) of the words "High" or "Low". This test will be performed under single and dual-task conditions.
Accuracy (number of correct responses out of the total responses) of Auditory stroop will be calculated. Higher accuracy indicates better performance. Higher values indicate better performance.
measure: Change in dual-task cost
time frame: Baseline (Week 0) and Immediate Post-training (Week 5)
description: Dual-task motor and cognitive cost will be calculated using the formula- [(Dual-task performance- Single Task performance)/Single task performance]. This will be calculated for dual-task performance during intentional postural sway, reactive balance control and gait conditions. Lower cost indicates better performance.
measure: Change in Interference in the reaction time
time frame: Baseline (Week 0) and Immediate Post-training (Week 5)
description: Interference in the reaction time via visual stroop task where the individual is expected to respond to the color in which the word is printed and not read the word. Performance will be identified via time taken to complete the test. Lower time indicate better performance.
measure: Change in language fluency
time frame: Baseline (Week 0) and Immediate Post-training (Week 5)
description: Language fluency via verbal and category task will be administered. Performance will be identified via the total number of appropriate words responded on each of the task. Higher values indicate better performance.
measure: Change in reaction time
time frame: Baseline (Week 0) and Immediate Post-training (Week 5)
description: The individual is asked to hit a key on the number keypad when a cue appears on the screen. Performance will be identified with time taken to hit the key after the individual sees the cue in seconds. Lower time indicate better performance.
measure: Change in paired associated learning
time frame: Baseline (Week 0) and Immediate Post-training (Week 5)
description: Paired associated learning via grid task will be administered. Accuracy (number of correct responses out of the total responses) will be represented in percentage. Higher value indicate better performance.
measure: Change in spatial working memory
time frame: Baseline (Week 0) and Immediate Post-training (Week 5)
description: Spatial working memory via unveil the star task will be administered. Performance will be identified via the total time (in seconds) to complete the task. Lower time indicate better performance.
measure: Change in working memory
time frame: Baseline (Week 0) and Immediate Post-training (Week 5)
description: List Sorting Memory test to evaluate working memory. This test requires the participant to recall and sequentially list the visually and orally presented stimuli. The accuracy of the participants response is computer generated. Higher value indicate better performance.
measure: Change in episodic memory
time frame: Baseline (Week 0) and Immediate Post-training (Week 5)
description: Picture sequence memory test will assess episodic memory of the individual. The number of adjacent pairs of pictures placed correctly will score a point. The scores are computer generated. Higher value indicate better performance.
measure: Change in accuracy of flanker inhibitory control and attention test
time frame: Baseline (Week 0) and Immediate Post-training (Week 5)
description: Flanker inhibitory control and attention test is used to evaluate the participants ability to inhibit the attention to the stimulus flanking it and focus on a particular stimulus. Accuracy of the responses are recorded and the scores are computer generated. Higher value indicate better performance.
measure: Change in cognitive flexibility and attention
time frame: Baseline (Week 0) and Immediate Post-training (Week 5)
description: Dimensional Change card sort assesses cognitive flexibility and attention. Participants are asked to match a series of bivalent pictures either by colors or shapes accordingly. Responses are computer recorded and accuracy scores are computer generated. Higher value indicate better performance.
measure: Change in processing speed
time frame: Baseline (Week 0) and Immediate Post-training (Week 5)
description: Pattern comparison processing speed test is used to evaluate the processing speed. The participants are expected to respond whether the two pictures side-by side are same or not the same. Accuracy will be recorded by the computer and scores are computer generated. Higher value indicate better performance.
measure: Changes in fractional anisotropy
time frame: Baseline (Week 0) and Immediate Post-training (Week 5)
description: Image acquisition will be performed in a 3T and 1.5T Magnetic resonance scanner (MR 750, GE healthcare, Milwaukee). Fractional anisotropy (FA) is a scalar value ranging from 0-1 and change from pre- to post-training will compared to determine the structural and functional connectivity. Increase in FA values post-training will indicate positive results of training.
measure: Berg Balance scale
time frame: Baseline (Week 0) and Immediate Post-training (Week 5)
description: Assess static and dynamic balance. This scale consists of the participant transferring from one chair to another, reaching forward, stepping up and down from a stepping stool, standing with eyes closed and open, one leg standing. It is a 14-item scale with each item score ranging from 0-4. Performance on the scale will be calculated on a total of 56. Less than 45 will indicate greater risk of falling.
measure: Change in physical activity level (Questionnaires)
time frame: Baseline (Week 0) and Immediate Post-training (Week 5)
description: Questionnaires such as Physical Activity Scale for elderly and activity specific balance confidence scale will be self-reported by the participant. Activity specific balance confidence scale consists of 16 items, and each item score ranges from 0-100. The total score with 0 confidence indicates no confidence and 100 with complete confidence.
measure: Change in physical activity level
time frame: Baseline (Week 0) and 4 weeks Post-training (Week 9)
description: Average number of steps taken a day by the individual prior to and after training
arm group label: VR Cognitive-motor-balance training
arm group type: Experimental
description: Virtual reality based cognitive-motor balance (VR-CogMoBal) training will be delivered using the commercially available Wii-Fit Nintendo in conjunction with cognitive training. All participants will undergo 12 sessions of training in a tapering manner for four weeks with 90 minutes of training per session, i.e., 5 sessions for the first week, 3 sessions for the second week, and 2 sessions for the third and fourth week. Each session will be divided into 3 sub-sessions, where each sub-session will consist of playing 4 games in conjunction with cognitive task. All the games will be performed using a Wii-Fit balance board in front of a TV screen.
intervention type: Behavioral
intervention name: VR Cognitive-motor-balance training
description: The participant will play four of the six balance board games Table tilt, Tightrope, Soccer, Balance bubble, Light Run and Basic Step (each game is max 1.5 minutes). Each game will be superimposed with any 3 of the 6 cognitive tasks (word list generation consisting of verbal fluency (VF) and category fluency (CF), digit recall (DR), analogies (AN), mental arithmetic (MA), repeated letter (RL). The cognitive tasks will be randomized making sure that all the cognitive tasks are played with all the games. The cognitive and balance board game scores will be noted on the scoring sheet for each session. A total 10 minutes rest interval between every sub-session will be mandatorily provided.
arm group label: VR Cognitive-motor-balance training
other name: VR-CogMoBal
other name: Dual-task training
criteria: 
gender: All
minimum age: 55 Years
maximum age: N/A
healthy volunteers: No
last name: Tanvi S Bhatt, PhD
role: Principal Investigator
affiliation: University of Illinois at Chicago
last name: Lakshmi Kannan, MS PT
phone: 3124133175
email: lkanna2@uic.edu
facility: 
status: Recruiting
contact: 
contact backup: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Illinois at Chicago
investigator full name: Tanvi Bhatt
investigator title: Associate Professor
mesh term: Cognitive Dysfunction
sharing ipd: No