<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/NCT04485507</url>
  </required_header>
  <id_info>
    <org_study_id>1904370750</org_study_id>
    <nct_id>NCT04485507</nct_id>
  </id_info>
  <brief_title>COgnitive Intervention to Restore Attention Using Nature Environment</brief_title>
  <acronym>CORE</acronym>
  <official_title>A Virtual Reality Intervention to Improve Attention in Heart Failure Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Indiana University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>American Heart Association</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Indiana 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>
      Heart failure is a prevalent and serious public health concern with the growing aging&#xD;
      population. Patients with heart failure often experience attention impairment that decreases&#xD;
      their ability to perform self-care and diminishes their health-related quality of life. In&#xD;
      past studies, 15 - 27% of heart failure patients had attention impairment. Attention is&#xD;
      fundamental to human activities including self-care management of heart failure. However,&#xD;
      cognitive interventions focusing on attention are scarce in heart failure literature. This&#xD;
      study focuses on developing a novel cognitive intervention specifically targeting improved&#xD;
      attention and testing its efficacy on improving attention, self-care, and health-related&#xD;
      quality of life.&#xD;
&#xD;
      The investigators in this study are asking the following 3 questions: 1) does the newly&#xD;
      developed cognitive intervention using immersive virtual reality technology (Nature-VR)&#xD;
      improve attention compared with the control condition (Urban-VR)?; 2) does Nature-VR&#xD;
      intervention improve HF self-care and health-related quality of life compared with Urban-VR&#xD;
      control condition?; and 3) are selected biological factors associated with attention function&#xD;
      in HF?&#xD;
&#xD;
      The virtual reality-based cognitive intervention (Nature-VR) can be an efficacious&#xD;
      intervention for the patients to use and enjoy without burdening already reduced attention.&#xD;
      This study has great potential to improve attention and prevent attention impairment, thereby&#xD;
      leading to healthier lives among heart failure patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Heart failure (HF) is a prevalent serious chronic illness that affects 6.5 million American.&#xD;
      Among HF patients, prevalence of attention impairment is reported as 15-27%. Attention is&#xD;
      fundamental to human activities including HF self-care. However, cognitive interventions&#xD;
      focusing on attention are scarce in HF. The investigators developed a new cognitive&#xD;
      intervention with immersive virtual reality technology and created a prototype of the virtual&#xD;
      reality-based natural restorative environment intervention (Nature-VR). The prototype was&#xD;
      feasible and showed larger effects in improving attention among 10 HF patients.&#xD;
&#xD;
      In this 2-group randomized controlled pilot study, specific aims are to: 1) examine&#xD;
      preliminary efficacy of Nature-VR compared with Urban-VR on improving attention; 2) examine&#xD;
      preliminary efficacy of Nature-VR compared with Urban-VR on HF self-care and health-related&#xD;
      quality of life; and 3) explore possible biomarkers of attention in HF. This study is&#xD;
      important and novel because this is the first intervention study targeting attention using&#xD;
      virtual reality technology and investigating possible biomarkers associated with attention in&#xD;
      HF patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 1, 2020</start_date>
  <completion_date type="Actual">June 8, 2022</completion_date>
  <primary_completion_date type="Actual">June 8, 2022</primary_completion_date>
  <phase>N/A</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>Two-group randomized controlled pilot study</intervention_model_description>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>Double (Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Changes in attention - Multi-Source Interference Task</measure>
    <time_frame>Baseline, 4 weeks, 8 weeks, 26 weeks, and 52 weeks</time_frame>
    <description>Performances on the computerized cognitive test of Multi-Source Interference Task will be examined in terms of speed and accuracy. Participants are instructed to identify the target number, which is different than the other 3 numbers provided on the computer screen. There are two types of trials, congruent and incongruent. Congruent trials have a target number that is always matched its position on the button (e.g., 100, 020, or 223), in contrast, incongruent trials have the target number that is never matched with it position in the button (e.g., 010, 233, or 232). Faster response time and lower error rates indicate better attention.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in attention - Digit Span Test</measure>
    <time_frame>Baseline, 4 weeks, 8 weeks, 26 weeks, and 52 weeks</time_frame>
    <description>Participants are instructed to remember the sequence of numbers the data collector told and repeat the numbers right after the instructor finished talking. This test has 2 subsets, Forward-repeat exactly the same sequence, and Backward-repeat the numbers in the backward from last to the first. More digits correctly repeated indicate better attention.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in attention - Trail Making Test</measure>
    <time_frame>Baseline, 4 weeks, 8 weeks, 26 weeks, and 52 weeks</time_frame>
    <description>This traditional cognitive test of attention is a paper-pencil based measure and has 2 parts. Part A requires participants to connect a series of randomly arrayed, distinct circles numbered 1 to 25 in correct order as quickly as possible. Part B requires participants to connect a series of 25 circles numbered 1 to 13 randomly intermixed with letters from A to L, alternating between numbers and letters, and proceeding in ascending order (e.g., 1-A-2-B-3 and so on). Faster response time in seconds indicates better attention.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in attention - Stroop Test</measure>
    <time_frame>Baseline, 4 weeks, 8 weeks, 26 weeks, and 52 weeks</time_frame>
    <description>Stroop Test is a color-word test measuring the ability to processe different visual features and ignore distractions. The test has 2 parts of reading letters of color names and colors of color names using 4 color names (i.e., red, blue, yellow, and green). Congruent trials have the same letters and colors of the color names (i.e., red in red color). Incongruent trials have different letters and colors of the color names (i.e., red in blue color). Faster response time and lower error rates indicate better attention.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in attention - Attentional Function Index</measure>
    <time_frame>Baseline, 4 weeks, 8 weeks, 26 weeks, and 52 weeks</time_frame>
    <description>This self-reported questionnaire has 13 items on 0 to 10 response scales asking effectiveness in behaviors requiring attention. Higher scores indicate better subjective attention</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in the Self-Care of Heart Failure Index (SCHFI)</measure>
    <time_frame>Baseline, 4 weeks, 8 weeks, 26 weeks, and 52 weeks</time_frame>
    <description>This self-reported questionnaire consists of 29 items divided into 3 scales measuring self-care maintenance, symptom perception, and self-care management. In addition, self-care confidence is measured by additional 10 items. Each scale is scored separately and standardized to achieve a possible score of 0 to 100. Higher scores indicate better self-care of HF.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Minnesota Living with Heart Failure Questionnaire (LHFQ)</measure>
    <time_frame>Baseline, 4 weeks, 8 weeks, 26 weeks, and 52 weeks</time_frame>
    <description>Minnesota Living with Heart Failure Questionnaire will be used to measure health-related quality of life. This self-report questionnaire consists of 21 items on which patients are asked to rate how their HF condition impacted their physical and emotional health. Lower scores indicate better HRQL.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Changes in serum brain-derived neurotrophic factor levels (serum BDNF)</measure>
    <time_frame>Baseline and 4 weeks</time_frame>
    <description>Venipuncture will be performed to draw the blood by following Indiana University general laboratory safety guidelines. Changes in the serum BDNF levels (ng/ml) and its associations with attention will be examined.</description>
  </other_outcome>
  <other_outcome>
    <measure>BDNF gene</measure>
    <time_frame>Baseline</time_frame>
    <description>Venupucture will be performed to draw the blood for the possible genetic biomarker. The frequency of BDNF Val66Met genotype (e.g., rs6265) will be examined and attention will be examined by the genotype.</description>
  </other_outcome>
  <other_outcome>
    <measure>Apolipoprotein (APOE) gene</measure>
    <time_frame>Baseline</time_frame>
    <description>Venupucture will be performed to draw the blood for the possible genetic biomarker. The 3 common allele of APOE (i.e., e2, e3, and e4) will be examined. The frequency of APOE genotypes (e.g., rs7412, rs429358) will be examined and attention will be examined by the genotype.</description>
  </other_outcome>
  <other_outcome>
    <measure>Dopamine receptor gene</measure>
    <time_frame>Baseline</time_frame>
    <description>Venupucture will be performed to draw the blood for the possible genetic biomarker. Specifically, dopamine receptor gene 4 (e.g., 48 bp VNTR) polymorphism and its association with attention will be examined.</description>
  </other_outcome>
  <other_outcome>
    <measure>Dopamine transporter gene</measure>
    <time_frame>Baseline</time_frame>
    <description>Venupucture will be performed to draw the blood for the possible genetic biomarker. The dopamine transporter gene (DAT1) (e.g., rs28363170 - 40 bp VNTR) polymorphism and its association with attention will be examined.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">74</enrollment>
  <condition>Heart Failure</condition>
  <condition>Cognitive Dysfunction</condition>
  <arm_group>
    <arm_group_label>Nature-VR</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Viewing 3D pictures of natural environments</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Urban-VR</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Viewing 3D pictures of urban environments</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Nature-VR</intervention_name>
    <description>Viewing 360 degree nature pictures delivered by a virtual reality headset for 10 minutes/day, 5 days/week for 4 weeks (total of 200 minutes).</description>
    <arm_group_label>Nature-VR</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Urban-VR</intervention_name>
    <description>Viewing 360 degree urban pictures delivered by a virtual reality headset for 10 minutes/day, 5 days/week for 4 weeks (total of 200 minutes).</description>
    <arm_group_label>Urban-VR</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  adults (&gt; 21 years)&#xD;
&#xD;
          -  diagnosed with chronic HF Stage C&#xD;
&#xD;
          -  able to communicate in English&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  uncorrected visual impairment&#xD;
&#xD;
          -  major neurological disease (e.g., Alzheimer disease, Parkinson's disease)&#xD;
&#xD;
          -  major psychiatric disease (e.g., schizophrenia, bipolar disease)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Indiana University School of Nursing</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>July 14, 2020</study_first_submitted>
  <study_first_submitted_qc>July 21, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 24, 2020</study_first_posted>
  <last_update_submitted>September 21, 2022</last_update_submitted>
  <last_update_submitted_qc>September 21, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 22, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Indiana University</investigator_affiliation>
    <investigator_full_name>Miyeon Jung</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Failure</mesh_term>
    <mesh_term>Cognitive Dysfunction</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT04485507
org study id: 1904370750
nct id: NCT04485507
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Heart failure is a prevalent and serious public health concern with the growing aging
      population. Patients with heart failure often experience attention impairment that decreases
      their ability to perform self-care and diminishes their health-related quality of life. In
      past studies, 15 - 27% of heart failure patients had attention impairment. Attention is
      fundamental to human activities including self-care management of heart failure. However,
      cognitive interventions focusing on attention are scarce in heart failure literature. This
      study focuses on developing a novel cognitive intervention specifically targeting improved
      attention and testing its efficacy on improving attention, self-care, and health-related
      quality of life.

      The investigators in this study are asking the following 3 questions: 1) does the newly
      developed cognitive intervention using immersive virtual reality technology (Nature-VR)
      improve attention compared with the control condition (Urban-VR)?; 2) does Nature-VR
      intervention improve HF self-care and health-related quality of life compared with Urban-VR
      control condition?; and 3) are selected biological factors associated with attention function
      in HF?

      The virtual reality-based cognitive intervention (Nature-VR) can be an efficacious
      intervention for the patients to use and enjoy without burdening already reduced attention.
      This study has great potential to improve attention and prevent attention impairment, thereby
      leading to healthier lives among heart failure patients.
Heart failure (HF) is a prevalent serious chronic illness that affects 6.5 million American.
      Among HF patients, prevalence of attention impairment is reported as 15-27%. Attention is
      fundamental to human activities including HF self-care. However, cognitive interventions
      focusing on attention are scarce in HF. The investigators developed a new cognitive
      intervention with immersive virtual reality technology and created a prototype of the virtual
      reality-based natural restorative environment intervention (Nature-VR). The prototype was
      feasible and showed larger effects in improving attention among 10 HF patients.

      In this 2-group randomized controlled pilot study, specific aims are to: 1) examine
      preliminary efficacy of Nature-VR compared with Urban-VR on improving attention; 2) examine
      preliminary efficacy of Nature-VR compared with Urban-VR on HF self-care and health-related
      quality of life; and 3) explore possible biomarkers of attention in HF. This study is
      important and novel because this is the first intervention study targeting attention using
      virtual reality technology and investigating possible biomarkers associated with attention in
      HF patients.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Two-group randomized controlled pilot study
primary purpose: Supportive Care
masking: Double (Investigator, Outcomes Assessor)
measure: Changes in attention - Multi-Source Interference Task
time frame: Baseline, 4 weeks, 8 weeks, 26 weeks, and 52 weeks
description: Performances on the computerized cognitive test of Multi-Source Interference Task will be examined in terms of speed and accuracy. Participants are instructed to identify the target number, which is different than the other 3 numbers provided on the computer screen. There are two types of trials, congruent and incongruent. Congruent trials have a target number that is always matched its position on the button (e.g., 100, 020, or 223), in contrast, incongruent trials have the target number that is never matched with it position in the button (e.g., 010, 233, or 232). Faster response time and lower error rates indicate better attention.
measure: Changes in attention - Digit Span Test
time frame: Baseline, 4 weeks, 8 weeks, 26 weeks, and 52 weeks
description: Participants are instructed to remember the sequence of numbers the data collector told and repeat the numbers right after the instructor finished talking. This test has 2 subsets, Forward-repeat exactly the same sequence, and Backward-repeat the numbers in the backward from last to the first. More digits correctly repeated indicate better attention.
measure: Changes in attention - Trail Making Test
time frame: Baseline, 4 weeks, 8 weeks, 26 weeks, and 52 weeks
description: This traditional cognitive test of attention is a paper-pencil based measure and has 2 parts. Part A requires participants to connect a series of randomly arrayed, distinct circles numbered 1 to 25 in correct order as quickly as possible. Part B requires participants to connect a series of 25 circles numbered 1 to 13 randomly intermixed with letters from A to L, alternating between numbers and letters, and proceeding in ascending order (e.g., 1-A-2-B-3 and so on). Faster response time in seconds indicates better attention.
measure: Changes in attention - Stroop Test
time frame: Baseline, 4 weeks, 8 weeks, 26 weeks, and 52 weeks
description: Stroop Test is a color-word test measuring the ability to processe different visual features and ignore distractions. The test has 2 parts of reading letters of color names and colors of color names using 4 color names (i.e., red, blue, yellow, and green). Congruent trials have the same letters and colors of the color names (i.e., red in red color). Incongruent trials have different letters and colors of the color names (i.e., red in blue color). Faster response time and lower error rates indicate better attention.
measure: Changes in attention - Attentional Function Index
time frame: Baseline, 4 weeks, 8 weeks, 26 weeks, and 52 weeks
description: This self-reported questionnaire has 13 items on 0 to 10 response scales asking effectiveness in behaviors requiring attention. Higher scores indicate better subjective attention
measure: Changes in the Self-Care of Heart Failure Index (SCHFI)
time frame: Baseline, 4 weeks, 8 weeks, 26 weeks, and 52 weeks
description: This self-reported questionnaire consists of 29 items divided into 3 scales measuring self-care maintenance, symptom perception, and self-care management. In addition, self-care confidence is measured by additional 10 items. Each scale is scored separately and standardized to achieve a possible score of 0 to 100. Higher scores indicate better self-care of HF.
measure: Changes in Minnesota Living with Heart Failure Questionnaire (LHFQ)
time frame: Baseline, 4 weeks, 8 weeks, 26 weeks, and 52 weeks
description: Minnesota Living with Heart Failure Questionnaire will be used to measure health-related quality of life. This self-report questionnaire consists of 21 items on which patients are asked to rate how their HF condition impacted their physical and emotional health. Lower scores indicate better HRQL.
measure: Changes in serum brain-derived neurotrophic factor levels (serum BDNF)
time frame: Baseline and 4 weeks
description: Venipuncture will be performed to draw the blood by following Indiana University general laboratory safety guidelines. Changes in the serum BDNF levels (ng/ml) and its associations with attention will be examined.
measure: BDNF gene
time frame: Baseline
description: Venupucture will be performed to draw the blood for the possible genetic biomarker. The frequency of BDNF Val66Met genotype (e.g., rs6265) will be examined and attention will be examined by the genotype.
measure: Apolipoprotein (APOE) gene
time frame: Baseline
description: Venupucture will be performed to draw the blood for the possible genetic biomarker. The 3 common allele of APOE (i.e., e2, e3, and e4) will be examined. The frequency of APOE genotypes (e.g., rs7412, rs429358) will be examined and attention will be examined by the genotype.
measure: Dopamine receptor gene
time frame: Baseline
description: Venupucture will be performed to draw the blood for the possible genetic biomarker. Specifically, dopamine receptor gene 4 (e.g., 48 bp VNTR) polymorphism and its association with attention will be examined.
measure: Dopamine transporter gene
time frame: Baseline
description: Venupucture will be performed to draw the blood for the possible genetic biomarker. The dopamine transporter gene (DAT1) (e.g., rs28363170 - 40 bp VNTR) polymorphism and its association with attention will be examined.
arm group label: Nature-VR
arm group type: Experimental
description: Viewing 3D pictures of natural environments
arm group label: Urban-VR
arm group type: Active Comparator
description: Viewing 3D pictures of urban environments
intervention type: Other
intervention name: Nature-VR
description: Viewing 360 degree nature pictures delivered by a virtual reality headset for 10 minutes/day, 5 days/week for 4 weeks (total of 200 minutes).
arm group label: Nature-VR
intervention type: Other
intervention name: Urban-VR
description: Viewing 360 degree urban pictures delivered by a virtual reality headset for 10 minutes/day, 5 days/week for 4 weeks (total of 200 minutes).
arm group label: Urban-VR
criteria: 
gender: All
minimum age: 21 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Indiana University
investigator full name: Miyeon Jung
investigator title: Assistant Professor
mesh term: Heart Failure
mesh term: Cognitive Dysfunction
sharing ipd: Undecided