<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/NCT03297827</url>
  </required_header>
  <id_info>
    <org_study_id>17-315</org_study_id>
    <nct_id>NCT03297827</nct_id>
  </id_info>
  <brief_title>Cytokine Registry Database of Stroke Patients</brief_title>
  <acronym>CRISP</acronym>
  <official_title>A Prospective Cytokine Registry Database of Stroke (Ischemic and Hemorrhagic) Patients.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of New Mexico</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of New Mexico</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>
      Various molecules (cytokines: interleukins, interferons and neural proteins) found in human&#xD;
      and animal blood are reported to be elevated in acute stroke (Ischemic and hemorrhagic).&#xD;
      Cytokines can be pro-inflammatory or anti-inflammatory. There are studies confirming level&#xD;
      changes in serum of humans in the setting of several rheumatologic and cardiovascular&#xD;
      diseases. As new molecular markers (cytokines and neural tissue markers) are established in&#xD;
      scientific literature, stroke scientists are interested to evaluate the role of these in the&#xD;
      pathophysiology of stroke. Investigators intend to study the role of these molecules in the&#xD;
      development of stroke.&#xD;
&#xD;
      Acute stroke treatment has advanced considerably in the last 10 years with the establishment&#xD;
      of comprehensive stroke centers and approval of neuro-interventional techniques. However, the&#xD;
      molecular advancement in stroke pathogenesis has yet to reach a milestone in the world of&#xD;
      stroke treatment. In our opinion, creating a database of acute stroke patients containing all&#xD;
      pertinent medical demographics and clinical information along with the laboratory data,&#xD;
      molecular levels of pertinent cytokines/neural factors from consenting patients, will help us&#xD;
      define and delineate the most relevant molecules that are altered in acute stroke patients&#xD;
      and can help us further improve us understanding of the role of these in acute stroke and&#xD;
      thereby hopefully help in the improvement of our understanding and management of stroke.&#xD;
      Moreover, analyzing the cytokines in stroke and ICH patients would help understand their role&#xD;
      in the acute phase, which may become potential therapeutic adjuncts for tPA and endovascular&#xD;
      thrombectomy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Stroke is the fifth cause of all-cause mortality in US http://www.cdc.gov/stroke/facts.htm .&#xD;
      Early identification and treatment not only prevent mortality but also morbidity. Recent&#xD;
      advancement in the imaging and diagnostic technique and novel therapeutic modalities has&#xD;
      dramatically helped to downgrade stroke from the list of top mortality index in the last 3&#xD;
      years. However, studies determining factors which help predict stroke outcome are still&#xD;
      underway and much work needs to be done in this direction. Many factors currently are used to&#xD;
      predict stroke outcome with varying results, for e.g. NIHSS is a good predictor of stroke&#xD;
      outcome at 3 months; however, we need better predictors, outcome scales or outcome measures&#xD;
      which are easy, reliable and has better specificity and sensitivity.&#xD;
&#xD;
      There is also some correlation of clinical and biochemical predictors in subarachnoid,&#xD;
      cerebral venous thrombosis including Hunt and Hess, SAH score, WFNS-SAH grading among others&#xD;
      with variable predictive quality. (Rosen et al; Neurocritical Care; April 2005, Volume 2,&#xD;
      Issue 2, pp 110- 118: Subarachnoid hemorrhage grading scales).&#xD;
&#xD;
      During the acute phase of focal cerebral ischemia, there is an elevation of thrombin activity&#xD;
      and a decline in fibrinolytic activity. Moreover, the role of pro-inflammatory cytokines has&#xD;
      been proven in the last few decades, as markers of inflammation have been closely studied in&#xD;
      mice models; there are indications that elevated levels correlate with the extent of ischemic&#xD;
      injury. Various interleukins were found to be elevated in most if not all patients with acute&#xD;
      ischemic stroke. Correlation of hemostatic (procoagulant and fibrinolytic markers) with&#xD;
      inflammatory markers is under discussion, with no confirmed common marker identified as of&#xD;
      yet.&#xD;
&#xD;
      As new cytokines and tissue markers are established in scientific literature, stroke&#xD;
      scientists are interested in evaluating the role of these markers in the pathophysiology of&#xD;
      stroke. The role of glial cell markers has been of remarkable interest. Recently, an&#xD;
      astrocyte marker S100B has shown association with infarct size, neurological outcome, and&#xD;
      prognosis. Moreover, analyzing the cytokines in stroke and ICH patients would help understand&#xD;
      their role in the acute phase, which may become potential therapeutic adjuncts for tpa and&#xD;
      endovascular thrombectomy. In summary, inflammation in acute stroke is an area of interest in&#xD;
      the recent years, with the theoretical benefit of aborting the inflammatory chain during&#xD;
      acute stroke might be useful in limiting stroke-related brain damage or hemorrhagic&#xD;
      transformation in acute stroke.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 15, 2019</start_date>
  <completion_date type="Actual">December 31, 2021</completion_date>
  <primary_completion_date type="Actual">December 31, 2021</primary_completion_date>
  <study_type>Observational [Patient Registry]</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <target_duration>3 Years</target_duration>
  <primary_outcome>
    <measure>Change in the cytokine levels at the 24-hour mark from the baseline levels done at the time of admission for acute stroke.</measure>
    <time_frame>24 Hours</time_frame>
    <description>Investigators will assess the variations in the levels of cytokines and inflammatory biomarkers at the 24-hour mark from the baseline levels done at the time of admission for acute stroke. Their correlation with each other may enable investigators to identify and streamline their efforts on only a few cytokines, interleukins, glial factors or metabolic products proved to be altered in acute stroke patients.</description>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">12</enrollment>
  <condition>Acute Stroke</condition>
  <condition>Acute Ischemic Stroke</condition>
  <condition>Ischemic Stroke</condition>
  <condition>Hemorrhagic Stroke</condition>
  <arm_group>
    <arm_group_label>Patients with stroke</arm_group_label>
    <description>Adult stroke patients with the stroke diagnosis will be recruited on admission to the University of New Mexico Hospital. Serum and Urine measurement of cytokines from two sets of serum and urine samples will be done on the admission and at the 24-hour mark respectively, form the specimens collected for the clinical purposes and are meant to be discarded. Consent will be taken from the patients to use these samples for our study.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Patients without stroke</arm_group_label>
    <description>Age/Sex matched adult control patients without the diagnosis of stroke, myocardial infarction, inflammatory flare, acute trauma, neurodegenerative or neuroinflammatory disease (AD, PD, TM, PSP, etc.) except MS will be recruited on admission to the University of New Mexico Hospital. Serum and Urine measurement of cytokines from two sets of serum and urine samples will be done on the admission and at the 24-hour mark respectively, form the specimens collected for the clinical purposes and are meant to be discarded. Consent will be taken from the patients to use these samples for our study.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Serum and Urine measurement of cytokines.</intervention_name>
    <description>To evaluate serum cytokine levels and identifying serum inflammatory markers (serum interleukin-33, IL-37, IL-36, IL-4, IL-6, IL-10, IL-17, IL-23, IL-1, TNF, PDGF, VEGFM TNFa, ANNULIN, MMP-9, MMP-12, NFk-B levels plus metabolic products like MPO, etc and glial factors like GMF, SI000B, GM6001) in patients with acute ischemic &amp; hemorrhagic stroke.</description>
    <arm_group_label>Patients with stroke</arm_group_label>
    <arm_group_label>Patients without stroke</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood Specimens Urine Specimens&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Two sets of serum samples will be obtained and analyzed; one upon admission to the&#xD;
        hospital, and the 2nd, the next morning after overnight fasting. Both sets of blood draw&#xD;
        are done for a clinical purpose, and any extra stored sample that is drawn and not used by&#xD;
        pathology will be used for the study. Twenty-five percent of the total stroke patient serum&#xD;
        samples will be matched by appropriate controls to confirm the level changes in stroke&#xD;
        patients. ELISA-PCR assays will be performed on serum samples.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. All stroke patients (hemorrhagic and ischemic) presenting within 24 hours of onset who&#xD;
             consent to our study.&#xD;
&#xD;
          2. Adult Male/Female patients ages &gt;18 years old&#xD;
&#xD;
          3. Patients whose standard stroke admission order sets are obtained for clinical care.&#xD;
&#xD;
          4. Patients with a history of MS may be included for future subanalysis.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. History of prior stroke or any other neurodegenerative or neuroinflammatory disease&#xD;
             (AD, PD, TM, PSP, etc.) except MS.&#xD;
&#xD;
          2. Individuals ages &lt;18 year&#xD;
&#xD;
          3. Pregnant women&#xD;
&#xD;
          4. Prisoners&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
  </eligibility>
  <overall_official>
    <last_name>Michel Torbey, MD, MPH</last_name>
    <role>Study Chair</role>
    <affiliation>University of New Mexico</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Atif Zafar, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of New Mexico</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Asad Ikram, MD</last_name>
    <role>Study Director</role>
    <affiliation>University of New Mexico</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Mudassir Farooqui, MD, MPH</last_name>
    <role>Study Director</role>
    <affiliation>University of New Mexico</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Neurology, University of New Mexico</name>
      <address>
        <city>Albuquerque</city>
        <state>New Mexico</state>
        <zip>87131-0007</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8422456/</url>
    <description>Cytokines, brain proteins, and growth factors in acute stroke patients: A pilot study</description>
  </link>
  <results_reference>
    <citation>Zafar A, Farooqui M, Ikram A, Suriya S, Kempuraj D, Khan M, Tasneem N, Qaryouti D, Quadri S, Adams HP, Ortega-Gutierrez S, Leira E, Zaheer A. Cytokines, brain proteins, and growth factors in acute stroke patients: A pilot study. Surg Neurol Int. 2021 Jul 27;12:366. doi: 10.25259/SNI_569_2021. eCollection 2021.</citation>
    <PMID>34513133</PMID>
  </results_reference>
  <verification_date>November 2020</verification_date>
  <study_first_submitted>September 21, 2017</study_first_submitted>
  <study_first_submitted_qc>September 26, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 29, 2017</study_first_posted>
  <last_update_submitted>January 25, 2022</last_update_submitted>
  <last_update_submitted_qc>January 25, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 8, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>diagnosis</keyword>
  <keyword>inflammatory biomarkers</keyword>
  <keyword>cytokines</keyword>
  <keyword>interleukin</keyword>
  <keyword>interferons</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stroke</mesh_term>
    <mesh_term>Ischemic Stroke</mesh_term>
    <mesh_term>Cerebral Infarction</mesh_term>
    <mesh_term>Hemorrhagic Stroke</mesh_term>
    <mesh_term>Ischemia</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/NCT03297827
org study id: 17-315
nct id: NCT03297827
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Various molecules (cytokines: interleukins, interferons and neural proteins) found in human
      and animal blood are reported to be elevated in acute stroke (Ischemic and hemorrhagic).
      Cytokines can be pro-inflammatory or anti-inflammatory. There are studies confirming level
      changes in serum of humans in the setting of several rheumatologic and cardiovascular
      diseases. As new molecular markers (cytokines and neural tissue markers) are established in
      scientific literature, stroke scientists are interested to evaluate the role of these in the
      pathophysiology of stroke. Investigators intend to study the role of these molecules in the
      development of stroke.

      Acute stroke treatment has advanced considerably in the last 10 years with the establishment
      of comprehensive stroke centers and approval of neuro-interventional techniques. However, the
      molecular advancement in stroke pathogenesis has yet to reach a milestone in the world of
      stroke treatment. In our opinion, creating a database of acute stroke patients containing all
      pertinent medical demographics and clinical information along with the laboratory data,
      molecular levels of pertinent cytokines/neural factors from consenting patients, will help us
      define and delineate the most relevant molecules that are altered in acute stroke patients
      and can help us further improve us understanding of the role of these in acute stroke and
      thereby hopefully help in the improvement of our understanding and management of stroke.
      Moreover, analyzing the cytokines in stroke and ICH patients would help understand their role
      in the acute phase, which may become potential therapeutic adjuncts for tPA and endovascular
      thrombectomy.
Stroke is the fifth cause of all-cause mortality in US http://www.cdc.gov/stroke/facts.htm .
      Early identification and treatment not only prevent mortality but also morbidity. Recent
      advancement in the imaging and diagnostic technique and novel therapeutic modalities has
      dramatically helped to downgrade stroke from the list of top mortality index in the last 3
      years. However, studies determining factors which help predict stroke outcome are still
      underway and much work needs to be done in this direction. Many factors currently are used to
      predict stroke outcome with varying results, for e.g. NIHSS is a good predictor of stroke
      outcome at 3 months; however, we need better predictors, outcome scales or outcome measures
      which are easy, reliable and has better specificity and sensitivity.

      There is also some correlation of clinical and biochemical predictors in subarachnoid,
      cerebral venous thrombosis including Hunt and Hess, SAH score, WFNS-SAH grading among others
      with variable predictive quality. (Rosen et al; Neurocritical Care; April 2005, Volume 2,
      Issue 2, pp 110- 118: Subarachnoid hemorrhage grading scales).

      During the acute phase of focal cerebral ischemia, there is an elevation of thrombin activity
      and a decline in fibrinolytic activity. Moreover, the role of pro-inflammatory cytokines has
      been proven in the last few decades, as markers of inflammation have been closely studied in
      mice models; there are indications that elevated levels correlate with the extent of ischemic
      injury. Various interleukins were found to be elevated in most if not all patients with acute
      ischemic stroke. Correlation of hemostatic (procoagulant and fibrinolytic markers) with
      inflammatory markers is under discussion, with no confirmed common marker identified as of
      yet.

      As new cytokines and tissue markers are established in scientific literature, stroke
      scientists are interested in evaluating the role of these markers in the pathophysiology of
      stroke. The role of glial cell markers has been of remarkable interest. Recently, an
      astrocyte marker S100B has shown association with infarct size, neurological outcome, and
      prognosis. Moreover, analyzing the cytokines in stroke and ICH patients would help understand
      their role in the acute phase, which may become potential therapeutic adjuncts for tpa and
      endovascular thrombectomy. In summary, inflammation in acute stroke is an area of interest in
      the recent years, with the theoretical benefit of aborting the inflammatory chain during
      acute stroke might be useful in limiting stroke-related brain damage or hemorrhagic
      transformation in acute stroke.
observational model: Cohort
time perspective: Prospective
measure: Change in the cytokine levels at the 24-hour mark from the baseline levels done at the time of admission for acute stroke.
time frame: 24 Hours
description: Investigators will assess the variations in the levels of cytokines and inflammatory biomarkers at the 24-hour mark from the baseline levels done at the time of admission for acute stroke. Their correlation with each other may enable investigators to identify and streamline their efforts on only a few cytokines, interleukins, glial factors or metabolic products proved to be altered in acute stroke patients.
arm group label: Patients with stroke
description: Adult stroke patients with the stroke diagnosis will be recruited on admission to the University of New Mexico Hospital. Serum and Urine measurement of cytokines from two sets of serum and urine samples will be done on the admission and at the 24-hour mark respectively, form the specimens collected for the clinical purposes and are meant to be discarded. Consent will be taken from the patients to use these samples for our study.
arm group label: Patients without stroke
description: Age/Sex matched adult control patients without the diagnosis of stroke, myocardial infarction, inflammatory flare, acute trauma, neurodegenerative or neuroinflammatory disease (AD, PD, TM, PSP, etc.) except MS will be recruited on admission to the University of New Mexico Hospital. Serum and Urine measurement of cytokines from two sets of serum and urine samples will be done on the admission and at the 24-hour mark respectively, form the specimens collected for the clinical purposes and are meant to be discarded. Consent will be taken from the patients to use these samples for our study.
intervention type: Other
intervention name: Serum and Urine measurement of cytokines.
description: To evaluate serum cytokine levels and identifying serum inflammatory markers (serum interleukin-33, IL-37, IL-36, IL-4, IL-6, IL-10, IL-17, IL-23, IL-1, TNF, PDGF, VEGFM TNFa, ANNULIN, MMP-9, MMP-12, NFk-B levels plus metabolic products like MPO, etc and glial factors like GMF, SI000B, GM6001) in patients with acute ischemic & hemorrhagic stroke.
arm group label: Patients with stroke
arm group label: Patients without stroke
Blood Specimens Urine Specimens
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
last name: Michel Torbey, MD, MPH
role: Study Chair
affiliation: University of New Mexico
last name: Atif Zafar, MD
role: Principal Investigator
affiliation: University of New Mexico
last name: Asad Ikram, MD
role: Study Director
affiliation: University of New Mexico
last name: Mudassir Farooqui, MD, MPH
role: Study Director
affiliation: University of New Mexico
facility: 
country: United States
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8422456/
description: Cytokines, brain proteins, and growth factors in acute stroke patients: A pilot study
citation: Zafar A, Farooqui M, Ikram A, Suriya S, Kempuraj D, Khan M, Tasneem N, Qaryouti D, Quadri S, Adams HP, Ortega-Gutierrez S, Leira E, Zaheer A. Cytokines, brain proteins, and growth factors in acute stroke patients: A pilot study. Surg Neurol Int. 2021 Jul 27;12:366. doi: 10.25259/SNI_569_2021. eCollection 2021.
PMID: 34513133
responsible party type: Sponsor
mesh term: Stroke
mesh term: Ischemic Stroke
mesh term: Cerebral Infarction
mesh term: Hemorrhagic Stroke
mesh term: Ischemia
sharing ipd: No