<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/NCT02983786</url>
  </required_header>
  <id_info>
    <org_study_id>819681</org_study_id>
    <nct_id>NCT02983786</nct_id>
  </id_info>
  <brief_title>Detection of Cerebral Ischemia With a Noninvasive Neurometabolic Optical Monitor</brief_title>
  <acronym>NNOM</acronym>
  <official_title>Detection of Cerebral Ischemia With a Noninvasive Neurometabolic Optical Monitor</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Pennsylvania</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Pennsylvania</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The goals of the project are to evaluate a noninvasive monitor of brain metabolism and blood&#xD;
      flow in critically ill humans. If validated, such a reliable noninvasive brain blood flow and&#xD;
      metabolism monitor, by allowing physiologic and pharmacologic decisions based on real-time&#xD;
      brain physiology, potentially will become an important tool for clinicians in their efforts&#xD;
      to prevent additional brain tissue death in patients admitted with stroke, brain hemorrhage&#xD;
      and traumatic brain injury.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Many critically ill patients are admitted to the hospital with no infarcted brain tissue and&#xD;
      yet, after a period of extremely intense and expensive critical care, the patients are&#xD;
      discharged with new hospital-acquired dead brain tissue, with associated life-long disability&#xD;
      or brain death. This situation arises from the critical barrier of there being no&#xD;
      straightforward bedside methods to monitor cerebral blood flow (CBF) and its adequacy during&#xD;
      progression of post-insult secondary brain damage. This is important because of the&#xD;
      expectation that decrements in CBF in dangerous excess of decrements in cerebral metabolic&#xD;
      rate for oxygen (CMRO2), if detected early, can be treated to avert brain infarction.&#xD;
      Clinical examples of this issue, among many others, include post ischemic stroke edema, post&#xD;
      thrombolysis hyperemia or occlusion, post SAH vasospasm, hyperemic and oligemic intracranial&#xD;
      hypertension after traumatic brain injury or stroke, ICH associated global ischemia, and&#xD;
      intra and post carotid endarterectomy oligemia and hyperperfusion.&#xD;
&#xD;
      Critical care physicians need a bedside monitor of CBF coupled to CMRO2. The CMRO2 data will&#xD;
      allow delineation of adequacy of CBF as occasionally CBF decrements are simply matching&#xD;
      changes in CMRO2. The lack of such monitoring capability has resulted in clinicians making&#xD;
      often not helpful therapeutic decisions directed to non-neurologic endpoints, e.g., blood&#xD;
      pressure, PaCO2 and so on, &quot;hoping&quot; that such interventions will have a desired effect on&#xD;
      brain perfusion and metabolism.&#xD;
&#xD;
      Diffuse Correlation Spectroscopy (DCS) and Diffuse Optical Spectroscopy (DOS) are promising&#xD;
      NNOM optical techniques under development at UPenn (Dr. Arjun Yodh) which can provide&#xD;
      continuous bedside quantitative CBF, CMRO2 and oxygen extraction fraction (OEF) information.&#xD;
      Determination of capability to detect anaerobic conditions, as the investigators propose&#xD;
      doing, will make feasible the notion of individualized CBF, CMRO2, and OEF measurement and&#xD;
      brain-directed therapeutic optimization by bedside caregivers. This will eventually support a&#xD;
      significant change in the way Neurocritical Care is practiced, titrating therapy to&#xD;
      neurophysiologic rather than cardiovascular/ pulmonary endpoints. UPenn research techniques&#xD;
      presently provide information on relative quantitative changes in CBF and CMRO2 from&#xD;
      baseline. The investigators propose also developing a method for measurement of absolute CBF&#xD;
      and CMRO2 and further validating the absolute CBF against invasive thermodilution (ThD) CBF&#xD;
      techniques. The investigators' long range goal and overall objective is to prevent&#xD;
      in-hospital brain tissue death through development of improved bedside CBF/ CMRO2/OEF (NNOM)&#xD;
      monitoring techniques.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>December 2015</start_date>
  <completion_date type="Actual">May 25, 2022</completion_date>
  <primary_completion_date type="Actual">October 2018</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Other</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>The outcome variable will be the degree of correlation of ThD (thermodilution) CBF with optical CBF (cerebral blood flow).</measure>
    <time_frame>12 days</time_frame>
    <description>Determine if the optical monitoring device's assessment of CBF is valid.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The outcome variable will be whether the optical monitoring system detects an anaerobic condition based on specific criteria of low ThD CBF, low brain PO2(PbrO2), and high microdialysis lactate pyruvate ratio ( LPR).</measure>
    <time_frame>12 Days</time_frame>
    <description>Determine if the optical monitoring system can detect an anaerobic adverse condition in the brain which might lead to neural injury.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>The outcome variable will be a determination of characteristics of trends in systemic and neurophysiologic data which predict the later development of an anaerobic condition in the brain.</measure>
    <time_frame>12 days</time_frame>
    <description>Predict the later onset of a brain anaerobic condition.</description>
  </other_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">29</enrollment>
  <condition>Traumatic Brain Injury</condition>
  <condition>Ischemic Stroke</condition>
  <condition>Intracerebral Hemorrhage</condition>
  <condition>Subarachnoid Hemorrhage</condition>
  <condition>Acute Anoxic Encephalopathy</condition>
  <arm_group>
    <arm_group_label>Non-Invasive Monitoring</arm_group_label>
    <description>One non-invasive optode patch will be placed adjacent to the area of invasive monitoring and the second patch will be placed contralaterally. (12 hrs. daily is chosen primarily for budgetary reasons). The information for the non-invasive technology will be compared to the invasive technology.&#xD;
ICG (Indocyanine Green) will be injected to derive absolute CBF and calibrate the DCS monitor to yield continuous absolute CBF. During each 12-hour monitoring session, for up to 14 days, the ICG will be injected at baseline(0.2 mg/kg,(4), every four hours (or less if signal is stable).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Indocyanine Green</intervention_name>
    <description>ICG will be injected to derive absolute CBF and calibrate the DCS monitor to yield continuous absolute CBF. During each 12-hour monitoring session, for up to 14 days, the ICG will be injected at baseline(0.2 mg/kg,(4), every four hours (or less if signal is stable).</description>
    <arm_group_label>Non-Invasive Monitoring</arm_group_label>
    <other_name>Indocyanine Green Injection</other_name>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Inclusion criteria will be age greater than or equal to 18 years, the diagnosis of SAH,&#xD;
        TBI, ICH, and/or PIAE after cardiac arrest (post cardiac arrest coma) with GCS less than or&#xD;
        equal to 8 (coma- clinical indications for invasive neuromonitoring), endotracheal&#xD;
        intubation, clinical indications for invasive neuromonitoring, and family/guardian informed&#xD;
        consent.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Inclusion criteria will be age greater than or equal to 18 years, the diagnosis of SAH,&#xD;
        TBI, ICH, and/or (PIAE) after cardiac arrest (post cardiac arrest coma) with GCS less than&#xD;
        or equal to 8, endotracheal intubation, clinical indications for invasive Neuromonitoring,&#xD;
        and family/guardian informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. coagulation or platelet problems which cannot be corrected based on clinical&#xD;
             indications&#xD;
&#xD;
          2. anatomic abnormalities in skull or brain tissue precluding appropriate placement of an&#xD;
             invasive brain monitor&#xD;
&#xD;
          3. ongoing CNS or scalp infection,&#xD;
&#xD;
          4. allergy to indocyanine green dye&#xD;
&#xD;
          5. pregnancy&#xD;
&#xD;
          6. lactation or pumping breast milk for the purpose of feeding an infant&#xD;
&#xD;
          7. increased bilirubin suggestive of cholestasis or biliary obstruction, (8) allergy to&#xD;
             iodide&#xD;
&#xD;
        (9) severity of injury which leads the team or family to conclude that further advance&#xD;
        medical care would be futile and limitation of the level of support is requested.&#xD;
&#xD;
        Woman of childbearing potential will be excluded by urine or serum pregnancy test prior to&#xD;
        conducting any study related procedures. . There is not a risk of pregnancy during this&#xD;
        study as comatose patients will be monitored 24 hours a day in Intensive Care Units which&#xD;
        have full visibility of patients.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>W. Andrew Kofke, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Pennsylvania Health System</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Pennylvania Health System</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</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>December 3, 2015</study_first_submitted>
  <study_first_submitted_qc>December 1, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 6, 2016</study_first_posted>
  <last_update_submitted>September 1, 2022</last_update_submitted>
  <last_update_submitted_qc>September 1, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 2, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Brain Injuries</mesh_term>
    <mesh_term>Ischemic Stroke</mesh_term>
    <mesh_term>Brain Injuries, Traumatic</mesh_term>
    <mesh_term>Brain Diseases</mesh_term>
    <mesh_term>Subarachnoid Hemorrhage</mesh_term>
    <mesh_term>Cerebral Hemorrhage</mesh_term>
    <mesh_term>Brain Ischemia</mesh_term>
    <mesh_term>Cerebral Infarction</mesh_term>
    <mesh_term>Hypoxia, Brain</mesh_term>
    <mesh_term>Hemorrhage</mesh_term>
    <mesh_term>Ischemia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>No, study data only remains with the study team. update reports will be submitted to the NIH, however individual patient data will not be included.</ipd_description>
  </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/NCT02983786
org study id: 819681
nct id: NCT02983786
lead sponsor: 
has dmc: Yes
The goals of the project are to evaluate a noninvasive monitor of brain metabolism and blood
      flow in critically ill humans. If validated, such a reliable noninvasive brain blood flow and
      metabolism monitor, by allowing physiologic and pharmacologic decisions based on real-time
      brain physiology, potentially will become an important tool for clinicians in their efforts
      to prevent additional brain tissue death in patients admitted with stroke, brain hemorrhage
      and traumatic brain injury.
Many critically ill patients are admitted to the hospital with no infarcted brain tissue and
      yet, after a period of extremely intense and expensive critical care, the patients are
      discharged with new hospital-acquired dead brain tissue, with associated life-long disability
      or brain death. This situation arises from the critical barrier of there being no
      straightforward bedside methods to monitor cerebral blood flow (CBF) and its adequacy during
      progression of post-insult secondary brain damage. This is important because of the
      expectation that decrements in CBF in dangerous excess of decrements in cerebral metabolic
      rate for oxygen (CMRO2), if detected early, can be treated to avert brain infarction.
      Clinical examples of this issue, among many others, include post ischemic stroke edema, post
      thrombolysis hyperemia or occlusion, post SAH vasospasm, hyperemic and oligemic intracranial
      hypertension after traumatic brain injury or stroke, ICH associated global ischemia, and
      intra and post carotid endarterectomy oligemia and hyperperfusion.

      Critical care physicians need a bedside monitor of CBF coupled to CMRO2. The CMRO2 data will
      allow delineation of adequacy of CBF as occasionally CBF decrements are simply matching
      changes in CMRO2. The lack of such monitoring capability has resulted in clinicians making
      often not helpful therapeutic decisions directed to non-neurologic endpoints, e.g., blood
      pressure, PaCO2 and so on, "hoping" that such interventions will have a desired effect on
      brain perfusion and metabolism.

      Diffuse Correlation Spectroscopy (DCS) and Diffuse Optical Spectroscopy (DOS) are promising
      NNOM optical techniques under development at UPenn (Dr. Arjun Yodh) which can provide
      continuous bedside quantitative CBF, CMRO2 and oxygen extraction fraction (OEF) information.
      Determination of capability to detect anaerobic conditions, as the investigators propose
      doing, will make feasible the notion of individualized CBF, CMRO2, and OEF measurement and
      brain-directed therapeutic optimization by bedside caregivers. This will eventually support a
      significant change in the way Neurocritical Care is practiced, titrating therapy to
      neurophysiologic rather than cardiovascular/ pulmonary endpoints. UPenn research techniques
      presently provide information on relative quantitative changes in CBF and CMRO2 from
      baseline. The investigators propose also developing a method for measurement of absolute CBF
      and CMRO2 and further validating the absolute CBF against invasive thermodilution (ThD) CBF
      techniques. The investigators' long range goal and overall objective is to prevent
      in-hospital brain tissue death through development of improved bedside CBF/ CMRO2/OEF (NNOM)
      monitoring techniques.
observational model: Other
time perspective: Prospective
measure: The outcome variable will be the degree of correlation of ThD (thermodilution) CBF with optical CBF (cerebral blood flow).
time frame: 12 days
description: Determine if the optical monitoring device's assessment of CBF is valid.
measure: The outcome variable will be whether the optical monitoring system detects an anaerobic condition based on specific criteria of low ThD CBF, low brain PO2(PbrO2), and high microdialysis lactate pyruvate ratio ( LPR).
time frame: 12 Days
description: Determine if the optical monitoring system can detect an anaerobic adverse condition in the brain which might lead to neural injury.
measure: The outcome variable will be a determination of characteristics of trends in systemic and neurophysiologic data which predict the later development of an anaerobic condition in the brain.
time frame: 12 days
description: Predict the later onset of a brain anaerobic condition.
arm group label: Non-Invasive Monitoring
description: One non-invasive optode patch will be placed adjacent to the area of invasive monitoring and the second patch will be placed contralaterally. (12 hrs. daily is chosen primarily for budgetary reasons). The information for the non-invasive technology will be compared to the invasive technology.
ICG (Indocyanine Green) will be injected to derive absolute CBF and calibrate the DCS monitor to yield continuous absolute CBF. During each 12-hour monitoring session, for up to 14 days, the ICG will be injected at baseline(0.2 mg/kg,(4), every four hours (or less if signal is stable).
intervention type: Drug
intervention name: Indocyanine Green
description: ICG will be injected to derive absolute CBF and calibrate the DCS monitor to yield continuous absolute CBF. During each 12-hour monitoring session, for up to 14 days, the ICG will be injected at baseline(0.2 mg/kg,(4), every four hours (or less if signal is stable).
arm group label: Non-Invasive Monitoring
other name: Indocyanine Green Injection
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: W. Andrew Kofke, MD
role: Principal Investigator
affiliation: University of Pennsylvania Health System
facility: 
country: United States
responsible party type: Sponsor
mesh term: Brain Injuries
mesh term: Ischemic Stroke
mesh term: Brain Injuries, Traumatic
mesh term: Brain Diseases
mesh term: Subarachnoid Hemorrhage
mesh term: Cerebral Hemorrhage
mesh term: Brain Ischemia
mesh term: Cerebral Infarction
mesh term: Hypoxia, Brain
mesh term: Hemorrhage
mesh term: Ischemia
sharing ipd: No
ipd description: No, study data only remains with the study team. update reports will be submitted to the NIH, however individual patient data will not be included.