<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/NCT02221466</url>
  </required_header>
  <id_info>
    <org_study_id>ENDOPAT-1-HBO-MH-2014</org_study_id>
    <nct_id>NCT02221466</nct_id>
  </id_info>
  <brief_title>Measurement of Endothelial Function With Peripheral Arterial Tonometry in Patients Undergoing Hyperbaric Oxygen Therapy</brief_title>
  <official_title>Measurements of Endothelial Function by Means of Peripheral Arterial Tonometry in Diabetic Foot Ulcer Patients Undergoing Hyperbaric Oxygen Therapy.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ole Hyldegaard</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Rigshospitalet, Denmark</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this clinical study is to test whether or not patients treated with HBOT for&#xD;
      diabetic foot ulcers will demonstrate measurable changes of the blood vessel function during&#xD;
      the course of HBOT treatments. , i.e. an expected increase in the reactive hyperemic index&#xD;
      (RHI) measured by the peripheral arterial tonometry (PAT).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Measurement and monitoring of endothelial function can be used for prediction of outcome in&#xD;
      acute, severe disease. Diabetic patients have a poorer peripheral vascular function measured&#xD;
      by peripheral arterial tonometry (PAT) as compared to normals, but the effect of hyperbaric&#xD;
      oxygen therapy (HBOT) on endothelial function in these patients is unknown. Measurement of&#xD;
      PAT in patients with diabetic foot ulcers undergoing HBOT, may help to improve treatment and&#xD;
      changes in the reactive hyperemic index (RHI) might correlate with wound healing in these&#xD;
      patients.&#xD;
&#xD;
      Peripheral arterial tonometer (PAT) has been shown to be an easy, fast and standardized&#xD;
      method for measuring the peripheral arterial endothelial function. The method is also&#xD;
      operator-independent and has a high reproducibility.&#xD;
&#xD;
      The PAT apparatus (ENDOPAT) measures the post-ischemic response to a five-minute blood flow&#xD;
      occlusion of the upper arm, and the relationship between the pre-and post-ischemic pulse&#xD;
      amplitude is expressed as a reactive hyperemic index (RHI). The normal RHI in young healthy&#xD;
      persons is more than 2, while in critically ill patients and patients with diabetes,&#xD;
      hypertension or heart disease it is significantly decreased.&#xD;
&#xD;
      The study aims to test whether or not patients treated with HBOT for diabetic foot ulcers&#xD;
      will demonstrate an improvement of the endothelial function in the peripheral vessels, i.e.&#xD;
      an increase in RHI measured by the PAT. Similarly, essential mediators of angiogenesis and&#xD;
      nitric oxide bioavailability will be measured in peripheral blood taken during the PAT&#xD;
      measurements which will be performed at the time of inclusion, before HBOT and subsequently&#xD;
      for each 10th HBOT session.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>February 2014</start_date>
  <completion_date type="Actual">January 21, 2016</completion_date>
  <primary_completion_date type="Actual">January 21, 2016</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>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Peripheral arterial tonometry (PAT)</measure>
    <time_frame>6 weeks</time_frame>
    <description>Changes in PAT measurements upon completion of HBOT sessions.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Peripheral arterial tonometry (PAT)</measure>
    <time_frame>18 weeks</time_frame>
    <description>Changes in PAT measurements upon completion of HBOT sessions after 12 weeks.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Nitric oxide and cytokine expression</measure>
    <time_frame>6 weeks</time_frame>
    <description>Measurement of nitric oxide bioavailability and levels of cytokine expression levels in serum after HBOT completion.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Nitric oxide and cytokine expression</measure>
    <time_frame>18 weeks</time_frame>
    <description>Measurement of nitric oxide bioavailability and levels of cytokine expression levels in serum after HBOT completion following 12 weeks.</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">45</enrollment>
  <condition>Diabetic Peripheral Vascular Disease</condition>
  <arm_group>
    <arm_group_label>diabetic patients</arm_group_label>
    <description>Diabetic patients given HBOT</description>
  </arm_group>
  <arm_group>
    <arm_group_label>None diabetic patients</arm_group_label>
    <description>None diabetic patients given HBOT</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Whole blood and serum.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Diabetic and none diabetic patients admitted for HBOT.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diabetic patients with foot ulcer&#xD;
&#xD;
          -  None diabetic patients&#xD;
&#xD;
          -  Age &gt; 18 years&#xD;
&#xD;
          -  Patients referred to hyperbaric oxygen therapy.&#xD;
&#xD;
          -  Patients who have given written informed consent to participate in the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who cannot cooperate to participate in the study&#xD;
&#xD;
          -  Patients who do not understand or speak Danish or English&#xD;
&#xD;
          -  Allergy to the materials used in the experiment.&#xD;
&#xD;
          -  Patients &lt; 18 years&#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>Ole Hyldegaard, MD, DMSci</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital Copenhagen, Rigshospitalet</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospital of Copenhagen - Rigshospitalet</name>
      <address>
        <city>Copenhagen</city>
        <state>Capitol Region</state>
        <zip>2100</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <reference>
    <citation>Londahl M, Katzman P, Nilsson A, Hammarlund C. Hyperbaric oxygen therapy facilitates healing of chronic foot ulcers in patients with diabetes. Diabetes Care. 2010 May;33(5):998-1003. doi: 10.2337/dc09-1754.</citation>
    <PMID>20427683</PMID>
  </reference>
  <reference>
    <citation>Patvardhan EA, Heffernan KS, Ruan JM, Soffler MI, Karas RH, Kuvin JT. Assessment of vascular endothelial function with peripheral arterial tonometry: information at your fingertips? Cardiol Rev. 2010 Jan-Feb;18(1):20-8. doi: 10.1097/CRD.0b013e3181c46a15.</citation>
    <PMID>20010335</PMID>
  </reference>
  <reference>
    <citation>Celermajer DS, Sorensen KE, Gooch VM, Spiegelhalter DJ, Miller OI, Sullivan ID, Lloyd JK, Deanfield JE. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet. 1992 Nov 7;340(8828):1111-5. doi: 10.1016/0140-6736(92)93147-f.</citation>
    <PMID>1359209</PMID>
  </reference>
  <reference>
    <citation>Brant LC, Barreto SM, Passos VM, Ribeiro AL. Reproducibility of peripheral arterial tonometry for the assessment of endothelial function in adults. J Hypertens. 2013 Oct;31(10):1984-90. doi: 10.1097/HJH.0b013e328362d913.</citation>
    <PMID>23751970</PMID>
  </reference>
  <reference>
    <citation>Bergstrom A, Staalso JM, Romner B, Olsen NV. Impaired endothelial function after aneurysmal subarachnoid haemorrhage correlates with arginine:asymmetric dimethylarginine ratio. Br J Anaesth. 2014 Feb;112(2):311-8. doi: 10.1093/bja/aet331. Epub 2013 Oct 1.</citation>
    <PMID>24085770</PMID>
  </reference>
  <reference>
    <citation>Mahmud FH, Van Uum S, Kanji N, Thiessen-Philbrook H, Clarson CL. Impaired endothelial function in adolescents with type 1 diabetes mellitus. J Pediatr. 2008 Apr;152(4):557-62. doi: 10.1016/j.jpeds.2007.08.044. Epub 2007 Nov 5.</citation>
    <PMID>18346515</PMID>
  </reference>
  <reference>
    <citation>Moerland M, Kales AJ, Schrier L, van Dongen MG, Bradnock D, Burggraaf J. Evaluation of the EndoPAT as a Tool to Assess Endothelial Function. Int J Vasc Med. 2012;2012:904141. doi: 10.1155/2012/904141. Epub 2012 Feb 14.</citation>
    <PMID>22500237</PMID>
  </reference>
  <reference>
    <citation>Eisenbud DE. Oxygen in wound healing: nutrient, antibiotic, signaling molecule, and therapeutic agent. Clin Plast Surg. 2012 Jul;39(3):293-310. doi: 10.1016/j.cps.2012.05.001. Epub 2012 Jun 2.</citation>
    <PMID>22732377</PMID>
  </reference>
  <reference>
    <citation>Boykin JV Jr, Baylis C. Hyperbaric oxygen therapy mediates increased nitric oxide production associated with wound healing: a preliminary study. Adv Skin Wound Care. 2007 Jul;20(7):382-8. doi: 10.1097/01.ASW.0000280198.81130.d5.</citation>
    <PMID>17620739</PMID>
  </reference>
  <verification_date>April 2017</verification_date>
  <study_first_submitted>August 19, 2014</study_first_submitted>
  <study_first_submitted_qc>August 19, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 20, 2014</study_first_posted>
  <last_update_submitted>April 27, 2017</last_update_submitted>
  <last_update_submitted_qc>April 27, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">April 28, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Rigshospitalet, Denmark</investigator_affiliation>
    <investigator_full_name>Ole Hyldegaard</investigator_full_name>
    <investigator_title>Associate Professor, Medical Director, MD, Ph.D, DMSci</investigator_title>
  </responsible_party>
  <keyword>diabetes</keyword>
  <keyword>foot</keyword>
  <keyword>wounds</keyword>
  <keyword>nitric oxide</keyword>
  <keyword>endothelium</keyword>
  <keyword>infection</keyword>
  <keyword>biological markers</keyword>
  <keyword>observational study</keyword>
  <keyword>hyperbaric oxygen</keyword>
  <keyword>ulcers</keyword>
  <keyword>cytokines</keyword>
  <keyword>inflammation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vascular Diseases</mesh_term>
    <mesh_term>Peripheral Vascular Diseases</mesh_term>
    <mesh_term>Peripheral Arterial Disease</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/NCT02221466
org study id: ENDOPAT-1-HBO-MH-2014
nct id: NCT02221466
lead sponsor: 
has dmc: No
The purpose of this clinical study is to test whether or not patients treated with HBOT for
      diabetic foot ulcers will demonstrate measurable changes of the blood vessel function during
      the course of HBOT treatments. , i.e. an expected increase in the reactive hyperemic index
      (RHI) measured by the peripheral arterial tonometry (PAT).
Measurement and monitoring of endothelial function can be used for prediction of outcome in
      acute, severe disease. Diabetic patients have a poorer peripheral vascular function measured
      by peripheral arterial tonometry (PAT) as compared to normals, but the effect of hyperbaric
      oxygen therapy (HBOT) on endothelial function in these patients is unknown. Measurement of
      PAT in patients with diabetic foot ulcers undergoing HBOT, may help to improve treatment and
      changes in the reactive hyperemic index (RHI) might correlate with wound healing in these
      patients.

      Peripheral arterial tonometer (PAT) has been shown to be an easy, fast and standardized
      method for measuring the peripheral arterial endothelial function. The method is also
      operator-independent and has a high reproducibility.

      The PAT apparatus (ENDOPAT) measures the post-ischemic response to a five-minute blood flow
      occlusion of the upper arm, and the relationship between the pre-and post-ischemic pulse
      amplitude is expressed as a reactive hyperemic index (RHI). The normal RHI in young healthy
      persons is more than 2, while in critically ill patients and patients with diabetes,
      hypertension or heart disease it is significantly decreased.

      The study aims to test whether or not patients treated with HBOT for diabetic foot ulcers
      will demonstrate an improvement of the endothelial function in the peripheral vessels, i.e.
      an increase in RHI measured by the PAT. Similarly, essential mediators of angiogenesis and
      nitric oxide bioavailability will be measured in peripheral blood taken during the PAT
      measurements which will be performed at the time of inclusion, before HBOT and subsequently
      for each 10th HBOT session.
observational model: Cohort
time perspective: Prospective
measure: Peripheral arterial tonometry (PAT)
time frame: 6 weeks
description: Changes in PAT measurements upon completion of HBOT sessions.
measure: Peripheral arterial tonometry (PAT)
time frame: 18 weeks
description: Changes in PAT measurements upon completion of HBOT sessions after 12 weeks.
measure: Nitric oxide and cytokine expression
time frame: 6 weeks
description: Measurement of nitric oxide bioavailability and levels of cytokine expression levels in serum after HBOT completion.
measure: Nitric oxide and cytokine expression
time frame: 18 weeks
description: Measurement of nitric oxide bioavailability and levels of cytokine expression levels in serum after HBOT completion following 12 weeks.
arm group label: diabetic patients
description: Diabetic patients given HBOT
arm group label: None diabetic patients
description: None diabetic patients given HBOT
Whole blood and serum.
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ole Hyldegaard, MD, DMSci
role: Principal Investigator
affiliation: University Hospital Copenhagen, Rigshospitalet
facility: 
country: Denmark
citation: Londahl M, Katzman P, Nilsson A, Hammarlund C. Hyperbaric oxygen therapy facilitates healing of chronic foot ulcers in patients with diabetes. Diabetes Care. 2010 May;33(5):998-1003. doi: 10.2337/dc09-1754.
PMID: 20427683
citation: Patvardhan EA, Heffernan KS, Ruan JM, Soffler MI, Karas RH, Kuvin JT. Assessment of vascular endothelial function with peripheral arterial tonometry: information at your fingertips? Cardiol Rev. 2010 Jan-Feb;18(1):20-8. doi: 10.1097/CRD.0b013e3181c46a15.
PMID: 20010335
citation: Celermajer DS, Sorensen KE, Gooch VM, Spiegelhalter DJ, Miller OI, Sullivan ID, Lloyd JK, Deanfield JE. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet. 1992 Nov 7;340(8828):1111-5. doi: 10.1016/0140-6736(92)93147-f.
PMID: 1359209
citation: Brant LC, Barreto SM, Passos VM, Ribeiro AL. Reproducibility of peripheral arterial tonometry for the assessment of endothelial function in adults. J Hypertens. 2013 Oct;31(10):1984-90. doi: 10.1097/HJH.0b013e328362d913.
PMID: 23751970
citation: Bergstrom A, Staalso JM, Romner B, Olsen NV. Impaired endothelial function after aneurysmal subarachnoid haemorrhage correlates with arginine:asymmetric dimethylarginine ratio. Br J Anaesth. 2014 Feb;112(2):311-8. doi: 10.1093/bja/aet331. Epub 2013 Oct 1.
PMID: 24085770
citation: Mahmud FH, Van Uum S, Kanji N, Thiessen-Philbrook H, Clarson CL. Impaired endothelial function in adolescents with type 1 diabetes mellitus. J Pediatr. 2008 Apr;152(4):557-62. doi: 10.1016/j.jpeds.2007.08.044. Epub 2007 Nov 5.
PMID: 18346515
citation: Moerland M, Kales AJ, Schrier L, van Dongen MG, Bradnock D, Burggraaf J. Evaluation of the EndoPAT as a Tool to Assess Endothelial Function. Int J Vasc Med. 2012;2012:904141. doi: 10.1155/2012/904141. Epub 2012 Feb 14.
PMID: 22500237
citation: Eisenbud DE. Oxygen in wound healing: nutrient, antibiotic, signaling molecule, and therapeutic agent. Clin Plast Surg. 2012 Jul;39(3):293-310. doi: 10.1016/j.cps.2012.05.001. Epub 2012 Jun 2.
PMID: 22732377
citation: Boykin JV Jr, Baylis C. Hyperbaric oxygen therapy mediates increased nitric oxide production associated with wound healing: a preliminary study. Adv Skin Wound Care. 2007 Jul;20(7):382-8. doi: 10.1097/01.ASW.0000280198.81130.d5.
PMID: 17620739
responsible party type: Sponsor-Investigator
investigator affiliation: Rigshospitalet, Denmark
investigator full name: Ole Hyldegaard
investigator title: Associate Professor, Medical Director, MD, Ph.D, DMSci
mesh term: Vascular Diseases
mesh term: Peripheral Vascular Diseases
mesh term: Peripheral Arterial Disease