<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/NCT01688505</url>
  </required_header>
  <id_info>
    <org_study_id>BPV-Hallym</org_study_id>
    <nct_id>NCT01688505</nct_id>
  </id_info>
  <brief_title>Visit-to-Visit Variability in Blood Pressure as a Predictor of Poor Cognitive Function</brief_title>
  <acronym>BPV-COG</acronym>
  <official_title>Multicenter Retrospective Study of Visit-to-Visit Variability in Blood Pressure as a Predictor of Poor Cognitive Function</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hallym University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hallym University Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Hypertension in midlife is an independent risk factor of late life cognitive dysfunction or&#xD;
      dementia. Chronic hypertension cause vascular damage and cerebral ischemia, which ultimately&#xD;
      gives rise to the cognitive dysfunction or dementia.&#xD;
&#xD;
      A recent study showed that high visit-to-visit variability in clinic systolic blood pressure&#xD;
      (BP) was a strong independent predictor of stroke. This finding suggests that high clinic&#xD;
      systolic BP variability itself as well as chronic hypertension may cause vascular damage and&#xD;
      cerebral ischemia. Therefore, high clinic SBP variability may be also an independent risk&#xD;
      factor of cognitive dysfunction or dementia.&#xD;
&#xD;
      Vascular damage leads to the diminished autoregulatory capacities of cerebral arteries. The&#xD;
      brain with the reduced autoregulatory capacity may be more vulnerable to BP fluctuation.&#xD;
      Therefore, high BP variability may be more harmful in patients with damaged vessels (for&#xD;
      example, in patients with cerebral small vessel disease).&#xD;
&#xD;
      Previous data about BP variability and cognition revealed very controversial. Some studies&#xD;
      showed poor cognition in patients with high BP variability, but others did not.&#xD;
&#xD;
      The previous studies were mostly based on cross-sectional designs, and performed in&#xD;
      small-sized heterogeneous population for primary prevention. The harmful effect of high BP&#xD;
      variability may be clearer in the population with damaged vascular bed, such as cerebral&#xD;
      small vessel disease. The previous studies usually used ambulatory BP monitoring (ABPM).&#xD;
      However, recent data suggested that variability in BP on ABPM may be a weaker predictor of&#xD;
      vascular events than be visit-to-visit variability in clinic BP.&#xD;
&#xD;
      The investigators sought to find whether high visit-to-visit variability in clinic BP is&#xD;
      related with poor cognitive function in patients with cerebral small vessel disease.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a retrospective cohort study.&#xD;
&#xD;
      We include patients with cerebral small vessel disease, documented on MRI from Jan 2006 to&#xD;
      Dec 2010, who have been regularly followed up.&#xD;
&#xD;
      We evaluate the patients' cognitive function after written informed consent.&#xD;
&#xD;
      We independently review patients' medical record and analyze MRI data. BP variability&#xD;
      parameters include standard deviation(SD, primary measuring parameter), coefficient of&#xD;
      variation, successive variation, average real variability (ARV), SD independent of&#xD;
      mean(SDIM), SV independent of mean(SVIM), and ARV independent of mean (ARVIM). We will adjust&#xD;
      following confounding variables: age, sex, level of education, vascular risk factors, mean&#xD;
      SBP and DBP, NIHSS score, and white matter lesion burden on T2-weighted MRI.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>May 2012</start_date>
  <completion_date type="Anticipated">February 2013</completion_date>
  <primary_completion_date type="Anticipated">February 2013</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Association between raw score of K-MMSE and visit-to-visit systolic BP variability</measure>
    <time_frame>Time from previous MRI documentation as small vessel disease to cognitive function evaluation; 1.5 to 7 years</time_frame>
    <description>Difference of mean K-MMSE raw scores between the highest and the lowest tertile group stratified by visit-to-visit systolic BP variability: Wilcoxon_Mann_Whitney test&#xD;
Binary logistic regression analysis for independent association between visit-to-visit systolic BP variability and low cognition, including confounding variables with p&lt;0.2 in univariate analysis (Low cognition, defined as the lowest tertile of K-MMSE raw score)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Association between raw score of K-MMSE and visit-to-visit diastolic BP variability</measure>
    <time_frame>Time from previous MRI documentation as small vessel disease to cognitive function evaluation; 1.5 to 7 years</time_frame>
    <description>Difference of mean K-MMSE raw scores between the highest and the lowest tertile group stratified by visit-to-visit diastolic BP variability: Wilcoxon_Mann_Whitney test&#xD;
Binary logistic regression analysis for independent association between visit-to-visit diastolic BP variability and low cognition, including confounding variables with p&lt;0.2 in univariate analysis (Low cognition, defined as the lowest tertile of K-MMSE raw score)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Association between raw scores of &quot;K-VCI NP 30-minute protocol&quot; sub-tests and visit-to-visit systolic BP variability</measure>
    <time_frame>Time from previous MRI documentation as small vessel disease to cognitive function evaluation; 1.5 to 7 years</time_frame>
    <description>Difference of mean &quot;K-VCI NP 30-minute protocol&quot; sub-tests' raw scores between the highest and the lowest tertile group stratified by visit-to-visit systolic BP variability: Wilcoxon_Mann_Whitney test&#xD;
Binary logistic regression analysis for independent association between visit-to-visit systolic BP variability and low cognition, including confounding variables with p&lt;0.2 in univariate analysis (Low cognition, defined as the lowest tertile of each &quot;K-VCI NP 30-minute protocol&quot; sub-test)&#xD;
&quot;K-VCIHS NP 30-minute protocol&quot; include Seoul Verbal Learning Test (SVLT), Semantic Fluency Test, Animal Phonemic Fluency Test, Digit Symbol-Coding (DSC), Geriatric Depression Scale (GDS), and Trail Making Test A &amp; B.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Association between raw scores of &quot;K-VCI NP 30-minute protocol&quot; sub-tests and visit-to-visit diastolic BP variability</measure>
    <time_frame>Time from previous MRI documentation as small vessel disease to cognitive function evaluation; 1.5 to 7 years</time_frame>
    <description>Difference of mean &quot;K-VCI NP 30-minute protocol&quot; sub-tests' raw scores between the highest and the lowest tertile group stratified by visit-to-visit diastolic BP variability: Wilcoxon_Mann_Whitney test&#xD;
Binary logistic regression analysis for independent association between visit-to-visit diastolic BP variability and low cognition, including confounding variables with p&lt;0.2 in univariate analysis (Low cognition, defined as the lowest tertile of each &quot;K-VCI NP 30-minute protocol&quot; sub-test)</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">140</enrollment>
  <condition>Cerebral Small Vessel Diseases</condition>
  <arm_group>
    <arm_group_label>Visit-to-visit BP variability</arm_group_label>
    <description>The highest, intermediate, and the lowest visit-to-visit BP variability (Tertile grouping)</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Outpatients of stroke clinic in secondary or tertiary hospitals&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with cerebral small vessel disease previously documented on MRI (definition&#xD;
             of small vessel disease - symptomatic lacunar infarction or white matter ischemic&#xD;
             lesion with one or more asymptomatic lacunes)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Incomplete clinic BP data (less than 6 BP readings during recent one year)&#xD;
&#xD;
          -  History of cardiovascular or cerebrovascular events during recent one year&#xD;
&#xD;
          -  Documented cerebral infarction from large artery atherosclerosis&#xD;
&#xD;
          -  Atrial fibrillation or cardiac disease with high risk of embolism&#xD;
&#xD;
          -  Significant medical, neurological, or psychiatric disease affecting cognition&#xD;
&#xD;
          -  Known dementia treated with acetylcholine esterase inhibitor or memantine&#xD;
&#xD;
          -  Patients without informed consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>60 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Ju-Hun Lee, MD.</last_name>
    <phone>82 2 2224 6285</phone>
    <email>leejuhun@hallym.or.kr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Kyung-Ho Yu, MD. PhD.</last_name>
    <email>ykh1030@hallym.or.kr</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Chuncheon Sacred Heart Hospital, Hallym University, College of Medicine</name>
      <address>
        <city>Chuncheon-si</city>
        <state>Gangwon-do</state>
        <zip>200-704</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Hui-Chul Choi, MD. PhD.</last_name>
      <email>dohchi@hallym.or.kr</email>
    </contact>
    <investigator>
      <last_name>Chul-Ho Kim, MD.</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hallym University Sacred Heart Hospital, Hallym University, College of Medicine</name>
      <address>
        <city>Anyang-si</city>
        <state>Gyeonggi-do</state>
        <zip>431-796</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Byung-Chul Lee, MD. PhD.</last_name>
      <email>ssbrain@hallym.or.kr</email>
    </contact>
    <investigator>
      <last_name>Kyung-Ho Yu, MD. PhD.</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Mi-Sun Oh, MD.</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Gangdong Sacred Heart Hospital, Hallym University, College of Medicine</name>
      <address>
        <city>Seoul</city>
        <zip>134-701</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ju-Hun Lee, MD.</last_name>
      <phone>82 2 2224 2695</phone>
      <email>leejuhun@hallym.or.kr</email>
    </contact>
    <investigator>
      <last_name>Joon-Hyun Shin, MD.</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hangang Sacred Heart Hospital, Hallym University, College of Medicine</name>
      <address>
        <city>Seoul</city>
        <zip>150-719</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Soo-Jin Cho, MD. PhD.</last_name>
      <email>soojinc@hallym.or.kr</email>
    </contact>
    <investigator>
      <last_name>Yang-Ki Minn, MD. PhD.</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Gangnam Sacred Heart Hospital, Hallym University, College of Medicine</name>
      <address>
        <city>Seoul</city>
        <zip>150-950</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>San Jung, MD.</last_name>
      <email>neurojs@hallym.or.kr</email>
    </contact>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>September 2012</verification_date>
  <study_first_submitted>September 16, 2012</study_first_submitted>
  <study_first_submitted_qc>September 19, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 20, 2012</study_first_posted>
  <last_update_submitted>September 19, 2012</last_update_submitted>
  <last_update_submitted_qc>September 19, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 20, 2012</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>cerebral small vessel diseases</keyword>
  <keyword>cognitive impairment</keyword>
  <keyword>Blood pressure variability</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cerebral Small Vessel Diseases</mesh_term>
  </condition_browse>
  <!-- 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/NCT01688505
org study id: BPV-Hallym
nct id: NCT01688505
lead sponsor: 
has dmc: No
Hypertension in midlife is an independent risk factor of late life cognitive dysfunction or
      dementia. Chronic hypertension cause vascular damage and cerebral ischemia, which ultimately
      gives rise to the cognitive dysfunction or dementia.

      A recent study showed that high visit-to-visit variability in clinic systolic blood pressure
      (BP) was a strong independent predictor of stroke. This finding suggests that high clinic
      systolic BP variability itself as well as chronic hypertension may cause vascular damage and
      cerebral ischemia. Therefore, high clinic SBP variability may be also an independent risk
      factor of cognitive dysfunction or dementia.

      Vascular damage leads to the diminished autoregulatory capacities of cerebral arteries. The
      brain with the reduced autoregulatory capacity may be more vulnerable to BP fluctuation.
      Therefore, high BP variability may be more harmful in patients with damaged vessels (for
      example, in patients with cerebral small vessel disease).

      Previous data about BP variability and cognition revealed very controversial. Some studies
      showed poor cognition in patients with high BP variability, but others did not.

      The previous studies were mostly based on cross-sectional designs, and performed in
      small-sized heterogeneous population for primary prevention. The harmful effect of high BP
      variability may be clearer in the population with damaged vascular bed, such as cerebral
      small vessel disease. The previous studies usually used ambulatory BP monitoring (ABPM).
      However, recent data suggested that variability in BP on ABPM may be a weaker predictor of
      vascular events than be visit-to-visit variability in clinic BP.

      The investigators sought to find whether high visit-to-visit variability in clinic BP is
      related with poor cognitive function in patients with cerebral small vessel disease.
This is a retrospective cohort study.

      We include patients with cerebral small vessel disease, documented on MRI from Jan 2006 to
      Dec 2010, who have been regularly followed up.

      We evaluate the patients' cognitive function after written informed consent.

      We independently review patients' medical record and analyze MRI data. BP variability
      parameters include standard deviation(SD, primary measuring parameter), coefficient of
      variation, successive variation, average real variability (ARV), SD independent of
      mean(SDIM), SV independent of mean(SVIM), and ARV independent of mean (ARVIM). We will adjust
      following confounding variables: age, sex, level of education, vascular risk factors, mean
      SBP and DBP, NIHSS score, and white matter lesion burden on T2-weighted MRI.
observational model: Cohort
time perspective: Retrospective
measure: Association between raw score of K-MMSE and visit-to-visit systolic BP variability
time frame: Time from previous MRI documentation as small vessel disease to cognitive function evaluation; 1.5 to 7 years
description: Difference of mean K-MMSE raw scores between the highest and the lowest tertile group stratified by visit-to-visit systolic BP variability: Wilcoxon_Mann_Whitney test
Binary logistic regression analysis for independent association between visit-to-visit systolic BP variability and low cognition, including confounding variables with p<0.2 in univariate analysis (Low cognition, defined as the lowest tertile of K-MMSE raw score)
measure: Association between raw score of K-MMSE and visit-to-visit diastolic BP variability
time frame: Time from previous MRI documentation as small vessel disease to cognitive function evaluation; 1.5 to 7 years
description: Difference of mean K-MMSE raw scores between the highest and the lowest tertile group stratified by visit-to-visit diastolic BP variability: Wilcoxon_Mann_Whitney test
Binary logistic regression analysis for independent association between visit-to-visit diastolic BP variability and low cognition, including confounding variables with p<0.2 in univariate analysis (Low cognition, defined as the lowest tertile of K-MMSE raw score)
measure: Association between raw scores of "K-VCI NP 30-minute protocol" sub-tests and visit-to-visit systolic BP variability
time frame: Time from previous MRI documentation as small vessel disease to cognitive function evaluation; 1.5 to 7 years
description: Difference of mean "K-VCI NP 30-minute protocol" sub-tests' raw scores between the highest and the lowest tertile group stratified by visit-to-visit systolic BP variability: Wilcoxon_Mann_Whitney test
Binary logistic regression analysis for independent association between visit-to-visit systolic BP variability and low cognition, including confounding variables with p<0.2 in univariate analysis (Low cognition, defined as the lowest tertile of each "K-VCI NP 30-minute protocol" sub-test)
"K-VCIHS NP 30-minute protocol" include Seoul Verbal Learning Test (SVLT), Semantic Fluency Test, Animal Phonemic Fluency Test, Digit Symbol-Coding (DSC), Geriatric Depression Scale (GDS), and Trail Making Test A & B.
measure: Association between raw scores of "K-VCI NP 30-minute protocol" sub-tests and visit-to-visit diastolic BP variability
time frame: Time from previous MRI documentation as small vessel disease to cognitive function evaluation; 1.5 to 7 years
description: Difference of mean "K-VCI NP 30-minute protocol" sub-tests' raw scores between the highest and the lowest tertile group stratified by visit-to-visit diastolic BP variability: Wilcoxon_Mann_Whitney test
Binary logistic regression analysis for independent association between visit-to-visit diastolic BP variability and low cognition, including confounding variables with p<0.2 in univariate analysis (Low cognition, defined as the lowest tertile of each "K-VCI NP 30-minute protocol" sub-test)
arm group label: Visit-to-visit BP variability
description: The highest, intermediate, and the lowest visit-to-visit BP variability (Tertile grouping)
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 60 Years
maximum age: 80 Years
healthy volunteers: No
last name: Ju-Hun Lee, MD.
phone: 82 2 2224 6285
email: leejuhun@hallym.or.kr
last name: Kyung-Ho Yu, MD. PhD.
email: ykh1030@hallym.or.kr
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
country: Korea, Republic of
responsible party type: Sponsor
mesh term: Cerebral Small Vessel Diseases