<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/NCT03815513</url>
  </required_header>
  <id_info>
    <org_study_id>201811003RINB</org_study_id>
    <nct_id>NCT03815513</nct_id>
  </id_info>
  <brief_title>Non-invasive Evaluation of Cerebrovascular Reactivity in Spontaneous Intracerebral Hemorrhage</brief_title>
  <official_title>Non-invasive Evaluation of Cerebrovascular Reactivity in Spontaneous Intracerebral Hemorrhage</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Taiwan University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Taiwan University Hospital</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Spontaneous intracerebral hemorrhage (ICH) remains a significant cause of morbidity and&#xD;
      mortality around the globe. The most common etiology of nontraumatic spontaneous ICH is&#xD;
      hypertensive arteriopathy (HA), while cerebral amyloid angiopathy (CAA) is the most prevalent&#xD;
      cause of spontaneous lobar ICH in the elderly. Both HA and CAA belong to the family of&#xD;
      cerebral small vessel disease (cSVD). cSVD involves pathological processes that affect the&#xD;
      arteries, arterioles, capillaries, and veins on the surface and beneath the brain. The&#xD;
      resultant changes of cSVD in the brain vasculatures can be detected with neuroimaging,&#xD;
      includes cerebral microbleeds, white matter hyperintensities, lacunes, dilated perivascular&#xD;
      spaces, and brain atrophy.&#xD;
&#xD;
      Investigators of this study have probe into various imaging markers in patients with cSVD.&#xD;
      Investigators found that the lacune and cerebral microbleeds location was related to distinct&#xD;
      underlying etiology of cSVD. Further, investigators utilized amyloid PET study to directly&#xD;
      quantified the cerebral amyloid burden, and demonstrated the correlation between amyloid&#xD;
      deposition and deep/superficial microbleeds ratio. The association between cerebellum&#xD;
      microbleeds, which is a novel marker for cSVD, and the underlying pathology in patient with&#xD;
      spontaneous ICH has been investigated. Investigators also summarized and published the&#xD;
      current research of different cSVD imaging markers and its implication on patient care.&#xD;
&#xD;
      Cerebrovascular reactivity (CVR) represents the phenomenon that cerebral vessels dilate or&#xD;
      constrict in response to stimuli, which provides insights into the vascular reserve&#xD;
      information. The vascular reserve parameter is complementary to steady-state vascular index,&#xD;
      such as cerebral perfusion or other neuroimaging markers. Measurement of CVR using advanced&#xD;
      MR techniques is an emerging technique with multiple potential clinical utilities, and&#xD;
      impaired autoregulation may contribute to the pathogenesis of cSVD. Recently, diminished CVR&#xD;
      under visual stimuli has been linked to vascular amyloid deposits and related vascular&#xD;
      dysfunction. Clarifying the mechanism of cSVD-related brain injury would be an important step&#xD;
      towards identifying candidate treatment approaches.&#xD;
&#xD;
      The goal of this study is to understand the features of CVR in patients with cSVD-related&#xD;
      spontaneous ICH, for the purpose of establishing new biomarkers in cSVD diagnosis and&#xD;
      understanding the underlying pathophysiology.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Anticipated">January 21, 2019</start_date>
  <completion_date type="Anticipated">December 31, 2020</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2020</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Both patient with intracerebral hemorrhage and healthy control will receive brain MRI with Dipyridamole stimulation for cerebrovascular reactivity measurement.</intervention_model_description>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Intracerebral hemorrhage recurrence</measure>
    <time_frame>The patients will be follow up in the outpatient clinic for 2 years.</time_frame>
    <description>Symptomatic intracerebral hemorrhage recurrence during follow-up</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Ischemic stroke recurrence</measure>
    <time_frame>The patients will be follow up in the outpatient clinic for 2 years.</time_frame>
    <description>Symptomatic ischemic stroke recurrence during follow-up</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Intracerebral Hemorrhage</condition>
  <arm_group>
    <arm_group_label>cases</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patient with spontaneous intracerebral hemorrhage</description>
  </arm_group>
  <arm_group>
    <arm_group_label>controls</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Healthy control without history of symptomatic cerebrovascular diseases</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>brain MRI</intervention_name>
    <description>both case and control groups received brain MRI to evaluate cerebrovascular reactivity</description>
    <arm_group_label>cases</arm_group_label>
    <arm_group_label>controls</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  age between 20-90 years-old&#xD;
&#xD;
          -  patient with spontaneous intracerebral hemorrhage or healthy control&#xD;
&#xD;
          -  consciousness clear&#xD;
&#xD;
          -  willing to receive brain MRI&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  renal failure or Creatinine &gt; 2mg/dl&#xD;
&#xD;
          -  coagulopathy or hepatic insufficiency&#xD;
&#xD;
          -  unstable vital sign under inotropic agents&#xD;
&#xD;
          -  allergy to Dipyridamole&#xD;
&#xD;
          -  pregnancy&#xD;
&#xD;
          -  asthma history&#xD;
&#xD;
          -  metal implant or cardiac pacemaker&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Bo-Ching Lee, MD</last_name>
    <phone>+886 972653442</phone>
    <email>bochinglee@gmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Hsin-Hsi Tsai, MD</last_name>
    <phone>+886 939916897</phone>
    <email>tsaihsinhsi@gmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>National Taiwan University Hospital</name>
      <address>
        <city>Taipei</city>
        <zip>10048</zip>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Bo-Ching Lee, MD</last_name>
    </contact>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <reference>
    <citation>Tsai HH, Pasi M, Tsai LK, Chen YF, Lee BC, Tang SC, Fotiadis P, Huang CY, Yen RF, Gurol ME, Jeng JS. Distribution of Lacunar Infarcts in Asians With Intracerebral Hemorrhage: A Magnetic Resonance Imaging and Amyloid Positron Emission Tomography Study. Stroke. 2018 Jun;49(6):1515-1517. doi: 10.1161/STROKEAHA.118.021539. Epub 2018 Apr 25.</citation>
    <PMID>29695464</PMID>
  </reference>
  <reference>
    <citation>Tsai HH, Tsai LK, Chen YF, Tang SC, Lee BC, Yen RF, Jeng JS. Correlation of Cerebral Microbleed Distribution to Amyloid Burden in Patients with Primary Intracerebral Hemorrhage. Sci Rep. 2017 Mar 17;7:44715. doi: 10.1038/srep44715.</citation>
    <PMID>28303922</PMID>
  </reference>
  <reference>
    <citation>Dumas A, Dierksen GA, Gurol ME, Halpin A, Martinez-Ramirez S, Schwab K, Rosand J, Viswanathan A, Salat DH, Polimeni JR, Greenberg SM. Functional magnetic resonance imaging detection of vascular reactivity in cerebral amyloid angiopathy. Ann Neurol. 2012 Jul;72(1):76-81. doi: 10.1002/ana.23566.</citation>
    <PMID>22829269</PMID>
  </reference>
  <reference>
    <citation>Fisher M, Vasilevko V, Passos GF, Ventura C, Quiring D, Cribbs DH. Therapeutic modulation of cerebral microhemorrhage in a mouse model of cerebral amyloid angiopathy. Stroke. 2011 Nov;42(11):3300-3. doi: 10.1161/STROKEAHA.111.626655. Epub 2011 Sep 8.</citation>
    <PMID>21903962</PMID>
  </reference>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>January 17, 2019</study_first_submitted>
  <study_first_submitted_qc>January 21, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 24, 2019</study_first_posted>
  <last_update_submitted>January 21, 2019</last_update_submitted>
  <last_update_submitted_qc>January 21, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 24, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Intracerebral hemorrhage</keyword>
  <keyword>MRI</keyword>
  <keyword>human</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cerebral Hemorrhage</mesh_term>
    <mesh_term>Hemorrhage</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/NCT03815513
org study id: 201811003RINB
nct id: NCT03815513
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
Spontaneous intracerebral hemorrhage (ICH) remains a significant cause of morbidity and
      mortality around the globe. The most common etiology of nontraumatic spontaneous ICH is
      hypertensive arteriopathy (HA), while cerebral amyloid angiopathy (CAA) is the most prevalent
      cause of spontaneous lobar ICH in the elderly. Both HA and CAA belong to the family of
      cerebral small vessel disease (cSVD). cSVD involves pathological processes that affect the
      arteries, arterioles, capillaries, and veins on the surface and beneath the brain. The
      resultant changes of cSVD in the brain vasculatures can be detected with neuroimaging,
      includes cerebral microbleeds, white matter hyperintensities, lacunes, dilated perivascular
      spaces, and brain atrophy.

      Investigators of this study have probe into various imaging markers in patients with cSVD.
      Investigators found that the lacune and cerebral microbleeds location was related to distinct
      underlying etiology of cSVD. Further, investigators utilized amyloid PET study to directly
      quantified the cerebral amyloid burden, and demonstrated the correlation between amyloid
      deposition and deep/superficial microbleeds ratio. The association between cerebellum
      microbleeds, which is a novel marker for cSVD, and the underlying pathology in patient with
      spontaneous ICH has been investigated. Investigators also summarized and published the
      current research of different cSVD imaging markers and its implication on patient care.

      Cerebrovascular reactivity (CVR) represents the phenomenon that cerebral vessels dilate or
      constrict in response to stimuli, which provides insights into the vascular reserve
      information. The vascular reserve parameter is complementary to steady-state vascular index,
      such as cerebral perfusion or other neuroimaging markers. Measurement of CVR using advanced
      MR techniques is an emerging technique with multiple potential clinical utilities, and
      impaired autoregulation may contribute to the pathogenesis of cSVD. Recently, diminished CVR
      under visual stimuli has been linked to vascular amyloid deposits and related vascular
      dysfunction. Clarifying the mechanism of cSVD-related brain injury would be an important step
      towards identifying candidate treatment approaches.

      The goal of this study is to understand the features of CVR in patients with cSVD-related
      spontaneous ICH, for the purpose of establishing new biomarkers in cSVD diagnosis and
      understanding the underlying pathophysiology.
allocation: Non-Randomized
intervention model: Single Group Assignment
intervention model description: Both patient with intracerebral hemorrhage and healthy control will receive brain MRI with Dipyridamole stimulation for cerebrovascular reactivity measurement.
primary purpose: Diagnostic
masking: None (Open Label)
measure: Intracerebral hemorrhage recurrence
time frame: The patients will be follow up in the outpatient clinic for 2 years.
description: Symptomatic intracerebral hemorrhage recurrence during follow-up
measure: Ischemic stroke recurrence
time frame: The patients will be follow up in the outpatient clinic for 2 years.
description: Symptomatic ischemic stroke recurrence during follow-up
arm group label: cases
arm group type: Experimental
description: Patient with spontaneous intracerebral hemorrhage
arm group label: controls
arm group type: Experimental
description: Healthy control without history of symptomatic cerebrovascular diseases
intervention type: Other
intervention name: brain MRI
description: both case and control groups received brain MRI to evaluate cerebrovascular reactivity
arm group label: cases
arm group label: controls
criteria: 
gender: All
minimum age: 20 Years
maximum age: 90 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Bo-Ching Lee, MD
phone: +886 972653442
email: bochinglee@gmail.com
last name: Hsin-Hsi Tsai, MD
phone: +886 939916897
email: tsaihsinhsi@gmail.com
facility: 
status: Recruiting
contact: 
country: Taiwan
citation: Tsai HH, Pasi M, Tsai LK, Chen YF, Lee BC, Tang SC, Fotiadis P, Huang CY, Yen RF, Gurol ME, Jeng JS. Distribution of Lacunar Infarcts in Asians With Intracerebral Hemorrhage: A Magnetic Resonance Imaging and Amyloid Positron Emission Tomography Study. Stroke. 2018 Jun;49(6):1515-1517. doi: 10.1161/STROKEAHA.118.021539. Epub 2018 Apr 25.
PMID: 29695464
citation: Tsai HH, Tsai LK, Chen YF, Tang SC, Lee BC, Yen RF, Jeng JS. Correlation of Cerebral Microbleed Distribution to Amyloid Burden in Patients with Primary Intracerebral Hemorrhage. Sci Rep. 2017 Mar 17;7:44715. doi: 10.1038/srep44715.
PMID: 28303922
citation: Dumas A, Dierksen GA, Gurol ME, Halpin A, Martinez-Ramirez S, Schwab K, Rosand J, Viswanathan A, Salat DH, Polimeni JR, Greenberg SM. Functional magnetic resonance imaging detection of vascular reactivity in cerebral amyloid angiopathy. Ann Neurol. 2012 Jul;72(1):76-81. doi: 10.1002/ana.23566.
PMID: 22829269
citation: Fisher M, Vasilevko V, Passos GF, Ventura C, Quiring D, Cribbs DH. Therapeutic modulation of cerebral microhemorrhage in a mouse model of cerebral amyloid angiopathy. Stroke. 2011 Nov;42(11):3300-3. doi: 10.1161/STROKEAHA.111.626655. Epub 2011 Sep 8.
PMID: 21903962
responsible party type: Sponsor
mesh term: Cerebral Hemorrhage
mesh term: Hemorrhage
sharing ipd: Undecided