<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/NCT02978560</url>
  </required_header>
  <id_info>
    <org_study_id>HP-00071920</org_study_id>
    <nct_id>NCT02978560</nct_id>
  </id_info>
  <brief_title>Indocyanine Green Tissue Perfusion Monitoring</brief_title>
  <official_title>Indocyanine Green Tissue Perfusion Monitoring</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Maryland, Baltimore</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Baltimore Medical &amp; Surgical Associates PA</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Maryland, Baltimore</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of this project is to demonstrate that fluorescence-mediated photoplethysmography&#xD;
      (FM-PPG) is capable of routinely acquiring the tissue perfusion data sufficient to detect and&#xD;
      monitor skin tissue perfusion anomalies.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Methods to reliably predict which cutaneous wounds will heal are unreliable and clinical&#xD;
      judgment inadequate. This is a problem for all health care providers and a common dilemma&#xD;
      when evaluating patients in the Emergency Department. While capillary blood perfusion of the&#xD;
      skin is a recognized requirement for healing, objective methods to reliably quantify this&#xD;
      necessary physiological parameter are lacking. In large part, this is due to difficulties&#xD;
      visualizing and recording capillary blood flow. Despite technical advances in blood flow&#xD;
      imaging the capillary circulation remains poorly characterized. That is, current methodology&#xD;
      can only image medium-to-large caliber vessels, not the small capillaries. The investigators&#xD;
      hypothesize that with new technology, objective assessment of capillary flow can be achieved&#xD;
      with fluorescence-mediated photoplethysmography (FM-PPG) methodology, and this evaluation can&#xD;
      be used to objectively determine which wounds will heal promptly versus require adjunctive&#xD;
      interventions.&#xD;
&#xD;
      FM-PPG is currently being used clinically in clinics worldwide as a way to image blood flow,&#xD;
      but the apparatus provides only a relative measurement. Thus, this investigation is&#xD;
      Observational in nature and not Interventional. With repeated evaluations over weeks, current&#xD;
      FM-PPG allows an assessment to be made on whether wound conditions are improving. The&#xD;
      investigators have a device containing new imaging software which, in theory, can offer&#xD;
      precise quantification of capillary blood flow. If true, a single measurement may provide the&#xD;
      data necessary to predict which patients are in danger of not healing and thus requiring&#xD;
      aggressive, and at times expensive or painful interventions and - even worse - limb&#xD;
      amputations. This protocol is to test proof-of-concept by first evaluating cutaneous&#xD;
      capillary follow in 30 normal, healthy individuals and then 30 individuals presenting for&#xD;
      treatment with a variety of skin wounds to a clinic.&#xD;
&#xD;
      FM-PPG methodology requires intravenous injection of a small amount of a fluorescent dye,&#xD;
      indocyanine green (ICG). ICG is an FDA-approved agent that has been safely used in over 4000&#xD;
      patients. The area of skin to be measured is positioned below a camera and low-power laser&#xD;
      instrument to take fluorescent pictures. The ICG is dissolved in sterile salt water for&#xD;
      injection and about one and one half tablespoons injected into a vein. Typically, the&#xD;
      measuring sequence consists of obtaining fluorescence images at the rate of approximately&#xD;
      30/second during a period of about 15 seconds. Following acquisition of the initial transit&#xD;
      angiogram sequence, several additional 15-second-long image sequences are then acquired&#xD;
      during the next half-hour, but without any additional injections. At about 60 seconds&#xD;
      following dye injection, about two teaspoons of venous blood is withdrawn. This blood is used&#xD;
      in the laboratory to determine the ICG dye concentration as a verification of the&#xD;
      concentration determined by the camera images as part of the FM-PPG software algorithm&#xD;
      (circulating dye concentration is needed in calculation of quantitative blood perfusion).&#xD;
&#xD;
      Since this study will be the first to employ a methodology capable of acquiring absolute&#xD;
      tissue blood perfusion data from multiple subjects, there exists no database to indicate the&#xD;
      normal range of variation in skin tissue perfusion that occurs in normal subjects. Since&#xD;
      abnormal perfusion cannot be clearly recognized until the normal range of variation has been&#xD;
      established, the first 30 subjects will be normal individuals. Then the following 30 subjects&#xD;
      will be patients undergoing wound healing therapy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Funding was never obtained&#xD;
  </why_stopped>
  <start_date>December 2016</start_date>
  <completion_date type="Anticipated">December 2018</completion_date>
  <primary_completion_date type="Anticipated">December 2018</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Indocyanine Green Tissue Perfusion Monitoring</measure>
    <time_frame>2 years</time_frame>
    <description>Flow measurements on normal skin and sites of diabetic neuropathic wounds</description>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">0</enrollment>
  <condition>Regional Blood Flow</condition>
  <condition>Wound Heal</condition>
  <arm_group>
    <arm_group_label>control</arm_group_label>
    <description>The source population for this cohort will be 30 healthy individuals with no know cardiovascular disease or wound healing defects. Subjects will be recruited by word-of-mouth, who receive no remuneration and who will be selected for the study on the basis of inclusion and exclusion criteria. They will undergo fluorescence-mediated photoplethysmography once.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Wound Group</arm_group_label>
    <description>The source population will be 30 patients who present to wound care clinic with Diabetic Foot Ulcers. Candidate subjects will have had a standard wound evaluation and medical history taken as a matter of their standard of care. On the basis of the evaluation, the physician-investigators will determine if the patient meets the eligibility criteria. If so, the study will be explained to the patient at that time, and Informed Consent will be obtained. 30 healthy subjects will also be included, recruited by word-of-mouth, who receive no remuneration and who will be selected for the study on the basis of the following inclusion and exclusion criteria. They will undergo fluorescence-mediated photoplethysmography once at the onset of their wound care.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>fluorescence-mediated photoplethysmography</intervention_name>
    <description>Indocyanine green dye (ICG) will be injected intravenously as a sterile solution at a dose of 0.5 mg/kg, and then imaging of skin will be done with a fluorescence camera. The ICG-angiogram sequence will consist of 1.5 x 2.0-cm field-of-view ICG fluorescence images acquired at the rate of approximately 30/sec during a period of about 15 seconds. Following acquisition of the initial transit angiogram sequence, several additional 15-second-long image sequences will be acquired during the next half-hour, but without any additional injections.</description>
    <arm_group_label>Wound Group</arm_group_label>
    <arm_group_label>control</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        60&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female subjects, of any ethnic background, who are at least 21 years of age&#xD;
             and have normal healthy skin (30 normal subjects) or patients with diabetic foot ulcer&#xD;
             lesions (30 patients).&#xD;
&#xD;
          2. All subjects must be willing and be able to comply with the protocol, and to provide&#xD;
             informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patient currently participating in any other drug or device investigational study.&#xD;
&#xD;
          2. Patient with significant liver or kidney disease.&#xD;
&#xD;
          3. Patient with known adverse reaction to indocyanine green or iodine.&#xD;
&#xD;
          4. Patient is pregnant or nursing.&#xD;
&#xD;
          5. Patient with peripheral vascular disease and an ankle-brachial index blood flow of 0.6&#xD;
             or less&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Stephen R Thom, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Maryland, College Park</affiliation>
  </overall_official>
  <verification_date>December 2019</verification_date>
  <study_first_submitted>November 23, 2016</study_first_submitted>
  <study_first_submitted_qc>November 28, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 1, 2016</study_first_posted>
  <last_update_submitted>December 9, 2019</last_update_submitted>
  <last_update_submitted_qc>December 9, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">December 11, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Maryland, Baltimore</investigator_affiliation>
    <investigator_full_name>Stephen Thom</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>August 15, 2023</submitted>
  </pending_results>
  <!-- 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/NCT02978560
org study id: HP-00071920
nct id: NCT02978560
lead sponsor: 
collaborator: 
has dmc: Yes
The aim of this project is to demonstrate that fluorescence-mediated photoplethysmography
      (FM-PPG) is capable of routinely acquiring the tissue perfusion data sufficient to detect and
      monitor skin tissue perfusion anomalies.
Methods to reliably predict which cutaneous wounds will heal are unreliable and clinical
      judgment inadequate. This is a problem for all health care providers and a common dilemma
      when evaluating patients in the Emergency Department. While capillary blood perfusion of the
      skin is a recognized requirement for healing, objective methods to reliably quantify this
      necessary physiological parameter are lacking. In large part, this is due to difficulties
      visualizing and recording capillary blood flow. Despite technical advances in blood flow
      imaging the capillary circulation remains poorly characterized. That is, current methodology
      can only image medium-to-large caliber vessels, not the small capillaries. The investigators
      hypothesize that with new technology, objective assessment of capillary flow can be achieved
      with fluorescence-mediated photoplethysmography (FM-PPG) methodology, and this evaluation can
      be used to objectively determine which wounds will heal promptly versus require adjunctive
      interventions.

      FM-PPG is currently being used clinically in clinics worldwide as a way to image blood flow,
      but the apparatus provides only a relative measurement. Thus, this investigation is
      Observational in nature and not Interventional. With repeated evaluations over weeks, current
      FM-PPG allows an assessment to be made on whether wound conditions are improving. The
      investigators have a device containing new imaging software which, in theory, can offer
      precise quantification of capillary blood flow. If true, a single measurement may provide the
      data necessary to predict which patients are in danger of not healing and thus requiring
      aggressive, and at times expensive or painful interventions and - even worse - limb
      amputations. This protocol is to test proof-of-concept by first evaluating cutaneous
      capillary follow in 30 normal, healthy individuals and then 30 individuals presenting for
      treatment with a variety of skin wounds to a clinic.

      FM-PPG methodology requires intravenous injection of a small amount of a fluorescent dye,
      indocyanine green (ICG). ICG is an FDA-approved agent that has been safely used in over 4000
      patients. The area of skin to be measured is positioned below a camera and low-power laser
      instrument to take fluorescent pictures. The ICG is dissolved in sterile salt water for
      injection and about one and one half tablespoons injected into a vein. Typically, the
      measuring sequence consists of obtaining fluorescence images at the rate of approximately
      30/second during a period of about 15 seconds. Following acquisition of the initial transit
      angiogram sequence, several additional 15-second-long image sequences are then acquired
      during the next half-hour, but without any additional injections. At about 60 seconds
      following dye injection, about two teaspoons of venous blood is withdrawn. This blood is used
      in the laboratory to determine the ICG dye concentration as a verification of the
      concentration determined by the camera images as part of the FM-PPG software algorithm
      (circulating dye concentration is needed in calculation of quantitative blood perfusion).

      Since this study will be the first to employ a methodology capable of acquiring absolute
      tissue blood perfusion data from multiple subjects, there exists no database to indicate the
      normal range of variation in skin tissue perfusion that occurs in normal subjects. Since
      abnormal perfusion cannot be clearly recognized until the normal range of variation has been
      established, the first 30 subjects will be normal individuals. Then the following 30 subjects
      will be patients undergoing wound healing therapy.
observational model: Case-Control
time perspective: Prospective
measure: Indocyanine Green Tissue Perfusion Monitoring
time frame: 2 years
description: Flow measurements on normal skin and sites of diabetic neuropathic wounds
arm group label: control
description: The source population for this cohort will be 30 healthy individuals with no know cardiovascular disease or wound healing defects. Subjects will be recruited by word-of-mouth, who receive no remuneration and who will be selected for the study on the basis of inclusion and exclusion criteria. They will undergo fluorescence-mediated photoplethysmography once.
arm group label: Wound Group
description: The source population will be 30 patients who present to wound care clinic with Diabetic Foot Ulcers. Candidate subjects will have had a standard wound evaluation and medical history taken as a matter of their standard of care. On the basis of the evaluation, the physician-investigators will determine if the patient meets the eligibility criteria. If so, the study will be explained to the patient at that time, and Informed Consent will be obtained. 30 healthy subjects will also be included, recruited by word-of-mouth, who receive no remuneration and who will be selected for the study on the basis of the following inclusion and exclusion criteria. They will undergo fluorescence-mediated photoplethysmography once at the onset of their wound care.
intervention type: Device
intervention name: fluorescence-mediated photoplethysmography
description: Indocyanine green dye (ICG) will be injected intravenously as a sterile solution at a dose of 0.5 mg/kg, and then imaging of skin will be done with a fluorescence camera. The ICG-angiogram sequence will consist of 1.5 x 2.0-cm field-of-view ICG fluorescence images acquired at the rate of approximately 30/sec during a period of about 15 seconds. Following acquisition of the initial transit angiogram sequence, several additional 15-second-long image sequences will be acquired during the next half-hour, but without any additional injections.
arm group label: Wound Group
arm group label: control
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 21 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Stephen R Thom, MD, PhD
role: Principal Investigator
affiliation: University of Maryland, College Park
responsible party type: Principal Investigator
investigator affiliation: University of Maryland, Baltimore
investigator full name: Stephen Thom
investigator title: Professor
sharing ipd: No
submitted: August 15, 2023