xml: <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/NCT06029348</url>
    </required_header>
    <id_info>
      <org_study_id>STUDY23030073</org_study_id>
      <secondary_id>R01HL169990</secondary_id>
      <nct_id>NCT06029348</nct_id>
    </id_info>
    <brief_title>Cerebrovascular Health and Resilience in Midlife</brief_title>
    <acronym>CHARM</acronym>
    <official_title>Cerebrovascular Health and Resilience in Midlife</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University of Pittsburgh</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
        <agency_class>NIH</agency_class>
      </collaborator>
    </sponsors>
    <source>University of Pittsburgh</source>
    <oversight_info>
      <has_dmc>Yes</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>
        This study examines cardiovascular responses to a brief psychological challenge under&#xD;
        laboratory conditions among adult volunteers. The study volunteers are asked to complete two&#xD;
        study sessions. In one session, the volunteers are asked to provide demographic and&#xD;
        health-related information via questionnaires and an interview. In that session, volunteers&#xD;
        would then be asked to undergo evaluations of their body composition, blood pressure, heart&#xD;
        rate, and other signs of cardiovascular function and health. Lastly, volunteers would be&#xD;
        asked to take part in a brief and challenging psychological task after a period of rest while&#xD;
        cardiovascular activity is measured. In the other session, volunteers are asked to undergo&#xD;
        magnetic resonance imaging and to complete neuropsychological tests of memory, attention, and&#xD;
        processing speed. In addition to these two sessions, volunteers are asked to complete online&#xD;
        questionnaires. The study is designed to examine associations between transient changes in&#xD;
        cardiovascular activity induced by the psychological task, measures of overall cardiovascular&#xD;
        health, and measures of cerebrovascular health measured by magnetic resonance imaging. Study&#xD;
        results are expected to provide new information about the relationships between&#xD;
        cardiovascular activity changes to psychological challenges and cardiovascular and&#xD;
        cerebrovascular health in adults.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This cross-sectional study examines the extent to which cardiovascular responses to the acute&#xD;
        experience of psychological stress relate to signs of cerebrovascular health detected on&#xD;
        magnetic resonance imaging. Study volunteers will include midlife adults who do not report&#xD;
        having a history of clinical cardiovascular disease or dementia. Study volunteers will be&#xD;
        asked to complete protocols to assess: behavioral, social, and biological correlates of&#xD;
        cardiovascular and cerebrovascular health; arterial stiffness, endothelial function, and&#xD;
        beat-to-beat blood pressure; cardiovascular changes to acute psychological stress; signs of&#xD;
        cerebrovascular health; and, neuropsychological test performance. Cardiovascular responses to&#xD;
        acute psychological stress will be examined in relation to indicators of brain function and&#xD;
        structure, as well as indicators of cardiac and vascular function. Study results may help to&#xD;
        increase knowledge about stress-related factors and cardiovascular sources of brain health.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 18, 2023</start_date>
    <completion_date type="Anticipated">June 30, 2029</completion_date>
    <primary_completion_date type="Anticipated">June 30, 2029</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>
      <intervention_model_description>The study is designed to measure cardiovascular responses to brief (~4 minute) mental arithmetic task (a psychological challenge) under laboratory conditions. Cardiovascular activity will be measured during (1) a resting period prior to the task (~5min), then (2) during the task(~4 min), and then (3) after the task is complete (~10min) for all study volunteers. Cardiovascular responses will be examine in relation to other study outcome measures.</intervention_model_description>
      <primary_purpose>Basic Science</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Change in systolic blood pressure (SBP) from baseline to task</measure>
      <time_frame>Mean SBPs for the computation of change scores will be computed from the average of the 5 min baseline period and average of the 4 min task period</time_frame>
      <description>The mean SBP from the baseline period will be subtracted from the mean of the task period.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>White matter hyperintensity burden</measure>
      <time_frame>Derived from one acquisition sequence within in a 50 min multimodal MRI protocol</time_frame>
      <description>White matter hyperintensity burden will be computed as the total sum of the voxels segmented as hyperintensities multiplied by voxel dimensions to yield a total score (units of mm-cubed).</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Hippocampal volume</measure>
      <time_frame>Derived from one acquisition sequence within a 50 min multimodal MRI protocol</time_frame>
      <description>Total bilateral hippocampal volume will be computed as the total sum of voxels automatically segmented.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Perivascular space volume</measure>
      <time_frame>Derived from one acquisition sequence in a 50 min multimodal MRI protocol</time_frame>
      <description>Total perivascular space volume will be computed from segmented brain blood vessel-tissue interfaces.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Pulse wave velocity</measure>
      <time_frame>5 minutes</time_frame>
      <description>Pulse wave velocity in m/s will be assessed by dual impedance cardiography as a non-invasive indicator of arterial stiffness. This measure will be derived from the 5 minute baseline period.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Spontaneous baroreflex sensitivity</measure>
      <time_frame>5 minutes</time_frame>
      <description>Spontaneous baroreflex sensitivity in ms/mmHg will be computed by the sequence method applied to beat-to-beat blood pressure and electrocardiogram recordings.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Endothelial function</measure>
      <time_frame>15 minutes</time_frame>
      <description>Endothelial-dependent vasodilation will be measured non-invasively in a reactive hyperemia protocol using digital thermal monitoring.</description>
    </primary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">450</enrollment>
    <condition>Psychological Stress</condition>
    <condition>Cardiovascular Diseases</condition>
    <condition>Cerebrovascular Disorders</condition>
    <arm_group>
      <arm_group_label>Paced Auditory Serial Addition Task</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>For the Paced Auditory Serial Addition Task, volunteers are presented with single digit numbers (1-9), and are instructed to add any given number to the previously presented number, and call out the answer. Volunteers are told that their performance is being monitored by research assistants. Volunteers are provided with a signaling device that they can use to discontinue testing. Lastly, participants will be asked to complete brief questionnaires to assess their levels of experienced threat, challenge, valence, arousal, and sense of control.</description>
    </arm_group>
    <intervention>
      <intervention_type>Behavioral</intervention_type>
      <intervention_name>Paced Auditory Serial Addition Task</intervention_name>
      <description>Study volunteers will be asked to complete a 4-minute Paced Auditory Serial Addition Task, which is a standardized task that is widely used to study cardiovascular responses to acute psychological challenges (or stressors) in a laboratory setting.</description>
      <arm_group_label>Paced Auditory Serial Addition Task</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Able to attend 2 study visits at the University of Pittsburgh campus in Oakland&#xD;
               (Pennsylvania)&#xD;
  &#xD;
            -  Able to read and speak English&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Uncontrolled hypertension (systolic blood pressure &gt;160 or diastolic blood pressure&#xD;
               &gt;100 mmHg)&#xD;
  &#xD;
            -  Current use of anticonvulsant, anti-Parkinson, neuroleptic, or antipsychotic&#xD;
               medications&#xD;
  &#xD;
            -  Current use of glucocorticoids (e.g., oral prednisone) or ephedrine&#xD;
  &#xD;
            -  Current chronic conditions of the lungs, liver and kidney, as well as cancer&#xD;
               (chemotherapy and radiation) treatment in the past 12 months (allowances are made for&#xD;
               non-melanoma skin cancer treatment, controlled asthma, and allergy inhalers)&#xD;
  &#xD;
            -  Self-reported major neurological disorders or brain injuries (e.g., multiple&#xD;
               sclerosis, cerebral palsy, major head injury)&#xD;
  &#xD;
            -  Self-reported psychotic illnesses (mania, bipolar disorder, schizophrenia)&#xD;
  &#xD;
            -  Current pregnancy or childbirth within the past 6 months&#xD;
  &#xD;
            -  Suspected mild cognitive impairment or dementia&#xD;
  &#xD;
            -  Self reported sleep apnea&#xD;
  &#xD;
            -  Self-reported history of myocardial infarction, stroke, or revascularization&#xD;
               procedures, as well as treatment for cardiac arrhythmias&#xD;
  &#xD;
            -  Self-reported lack of comfort to undergo MRI testing&#xD;
  &#xD;
            -  Presence of implants or objects that are unsafe for MRI (e.g., tattooed eyeliner), as&#xD;
               well as any other contraindications that would prevent MRI testing&#xD;
  &#xD;
            -  Self-reported lack of comfort to undergo the laboratory math task&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>40 Years</minimum_age>
      <maximum_age>59 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Peter J Gianaros, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>University of Pittsburgh</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Peter J Gianaros, PhD</last_name>
      <phone>412-624-4500</phone>
      <email>gianaros@pitt.edu</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Sara Boyko, BS</last_name>
      <phone>412-648-9047</phone>
      <email>snyderse@pitt.edu</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>University of Pittsburgh</name>
        <address>
          <city>Pittsburgh</city>
          <state>Pennsylvania</state>
          <zip>15213</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Sara Boyko, BS</last_name>
      </contact>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 31, 2023</study_first_submitted>
    <study_first_submitted_qc>August 31, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 8, 2023</study_first_posted>
    <last_update_submitted>August 31, 2023</last_update_submitted>
    <last_update_submitted_qc>August 31, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 8, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>University of Pittsburgh</investigator_affiliation>
      <investigator_full_name>Peter Gianaros</investigator_full_name>
      <investigator_title>Professor</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Cerebrovascular Disorders</mesh_term>
      <mesh_term>Cardiovascular Diseases</mesh_term>
      <mesh_term>Stress, Psychological</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>De-identified individual participant data that comprise primary and secondary study outcomes will be made available with data dictionaries via the University of Pittsburgh's repository, D-Scholarship@Pitt. This repository provides indefinite storage and accessibility. Along with de-identified data, other shared resources will include a description of data collection methods and study code book; a description of the data files; and descriptions of data use conditions. Statistical scripts will be deposited as appropriate following publication of manuscripts bearing on the aims of the study. All publications will include information on the location of study data and accessibility. Requests by researchers for other de-identified data will be facilitated by completion of a Data Use Agreement, as well as provision of a methodologically sound proposal and approval from their institution.</ipd_description>
      <ipd_info_type>Study Protocol</ipd_info_type>
      <ipd_time_frame>Data are anticipated to become available within 12 months after the publication of findings bearing on the Specific Aims of R01HL169990</ipd_time_frame>
      <ipd_access_criteria>All presentations and publications will include information on the location of study data and its public accessibility for research use. The criteria for certain requests of de-identified data will involve the completion of a Data Use Agreement, https://www.osp.pitt.edu/osp-teams/clinical-corporate-contract-services/negotiations/data-use-agreements-duas</ipd_access_criteria>
      <ipd_url>https://d-scholarship.pitt.edu/</ipd_url>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06029348
  org study id: STUDY23030073
  secondary id: R01HL169990
  nct id: NCT06029348
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  This study examines cardiovascular responses to a brief psychological challenge under
        laboratory conditions among adult volunteers. The study volunteers are asked to complete two
        study sessions. In one session, the volunteers are asked to provide demographic and
        health-related information via questionnaires and an interview. In that session, volunteers
        would then be asked to undergo evaluations of their body composition, blood pressure, heart
        rate, and other signs of cardiovascular function and health. Lastly, volunteers would be
        asked to take part in a brief and challenging psychological task after a period of rest while
        cardiovascular activity is measured. In the other session, volunteers are asked to undergo
        magnetic resonance imaging and to complete neuropsychological tests of memory, attention, and
        processing speed. In addition to these two sessions, volunteers are asked to complete online
        questionnaires. The study is designed to examine associations between transient changes in
        cardiovascular activity induced by the psychological task, measures of overall cardiovascular
        health, and measures of cerebrovascular health measured by magnetic resonance imaging. Study
        results are expected to provide new information about the relationships between
        cardiovascular activity changes to psychological challenges and cardiovascular and
        cerebrovascular health in adults.
  This cross-sectional study examines the extent to which cardiovascular responses to the acute
        experience of psychological stress relate to signs of cerebrovascular health detected on
        magnetic resonance imaging. Study volunteers will include midlife adults who do not report
        having a history of clinical cardiovascular disease or dementia. Study volunteers will be
        asked to complete protocols to assess: behavioral, social, and biological correlates of
        cardiovascular and cerebrovascular health; arterial stiffness, endothelial function, and
        beat-to-beat blood pressure; cardiovascular changes to acute psychological stress; signs of
        cerebrovascular health; and, neuropsychological test performance. Cardiovascular responses to
        acute psychological stress will be examined in relation to indicators of brain function and
        structure, as well as indicators of cardiac and vascular function. Study results may help to
        increase knowledge about stress-related factors and cardiovascular sources of brain health.
  allocation: N/A
  intervention model: Single Group Assignment
  intervention model description: The study is designed to measure cardiovascular responses to brief (~4 minute) mental arithmetic task (a psychological challenge) under laboratory conditions. Cardiovascular activity will be measured during (1) a resting period prior to the task (~5min), then (2) during the task(~4 min), and then (3) after the task is complete (~10min) for all study volunteers. Cardiovascular responses will be examine in relation to other study outcome measures.
  primary purpose: Basic Science
  masking: None (Open Label)
  measure: Change in systolic blood pressure (SBP) from baseline to task
  time frame: Mean SBPs for the computation of change scores will be computed from the average of the 5 min baseline period and average of the 4 min task period
  description: The mean SBP from the baseline period will be subtracted from the mean of the task period.
  measure: White matter hyperintensity burden
  time frame: Derived from one acquisition sequence within in a 50 min multimodal MRI protocol
  description: White matter hyperintensity burden will be computed as the total sum of the voxels segmented as hyperintensities multiplied by voxel dimensions to yield a total score (units of mm-cubed).
  measure: Hippocampal volume
  time frame: Derived from one acquisition sequence within a 50 min multimodal MRI protocol
  description: Total bilateral hippocampal volume will be computed as the total sum of voxels automatically segmented.
  measure: Perivascular space volume
  time frame: Derived from one acquisition sequence in a 50 min multimodal MRI protocol
  description: Total perivascular space volume will be computed from segmented brain blood vessel-tissue interfaces.
  measure: Pulse wave velocity
  time frame: 5 minutes
  description: Pulse wave velocity in m/s will be assessed by dual impedance cardiography as a non-invasive indicator of arterial stiffness. This measure will be derived from the 5 minute baseline period.
  measure: Spontaneous baroreflex sensitivity
  time frame: 5 minutes
  description: Spontaneous baroreflex sensitivity in ms/mmHg will be computed by the sequence method applied to beat-to-beat blood pressure and electrocardiogram recordings.
  measure: Endothelial function
  time frame: 15 minutes
  description: Endothelial-dependent vasodilation will be measured non-invasively in a reactive hyperemia protocol using digital thermal monitoring.
  arm group label: Paced Auditory Serial Addition Task
  arm group type: Experimental
  description: For the Paced Auditory Serial Addition Task, volunteers are presented with single digit numbers (1-9), and are instructed to add any given number to the previously presented number, and call out the answer. Volunteers are told that their performance is being monitored by research assistants. Volunteers are provided with a signaling device that they can use to discontinue testing. Lastly, participants will be asked to complete brief questionnaires to assess their levels of experienced threat, challenge, valence, arousal, and sense of control.
  intervention type: Behavioral
  intervention name: Paced Auditory Serial Addition Task
  description: Study volunteers will be asked to complete a 4-minute Paced Auditory Serial Addition Task, which is a standardized task that is widely used to study cardiovascular responses to acute psychological challenges (or stressors) in a laboratory setting.
  arm group label: Paced Auditory Serial Addition Task
  criteria: 
  gender: All
  minimum age: 40 Years
  maximum age: 59 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Peter J Gianaros, PhD
  role: Principal Investigator
  affiliation: University of Pittsburgh
  last name: Peter J Gianaros, PhD
  phone: 412-624-4500
  email: gianaros@pitt.edu
  last name: Sara Boyko, BS
  phone: 412-648-9047
  email: snyderse@pitt.edu
  facility: 
  contact: 
  country: United States
  responsible party type: Principal Investigator
  investigator affiliation: University of Pittsburgh
  investigator full name: Peter Gianaros
  investigator title: Professor
  mesh term: Cerebrovascular Disorders
  mesh term: Cardiovascular Diseases
  mesh term: Stress, Psychological
  sharing ipd: Yes
  ipd description: De-identified individual participant data that comprise primary and secondary study outcomes will be made available with data dictionaries via the University of Pittsburgh's repository, D-Scholarship@Pitt. This repository provides indefinite storage and accessibility. Along with de-identified data, other shared resources will include a description of data collection methods and study code book; a description of the data files; and descriptions of data use conditions. Statistical scripts will be deposited as appropriate following publication of manuscripts bearing on the aims of the study. All publications will include information on the location of study data and accessibility. Requests by researchers for other de-identified data will be facilitated by completion of a Data Use Agreement, as well as provision of a methodologically sound proposal and approval from their institution.
  ipd info type: Study Protocol
  ipd time frame: Data are anticipated to become available within 12 months after the publication of findings bearing on the Specific Aims of R01HL169990
  ipd access criteria: All presentations and publications will include information on the location of study data and its public accessibility for research use. The criteria for certain requests of de-identified data will involve the completion of a Data Use Agreement, https://www.osp.pitt.edu/osp-teams/clinical-corporate-contract-services/negotiations/data-use-agreements-duas
  ipd url: https://d-scholarship.pitt.edu/