<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/NCT03298295</url>
  </required_header>
  <id_info>
    <org_study_id>IRCATT</org_study_id>
    <nct_id>NCT03298295</nct_id>
  </id_info>
  <brief_title>Inflammatory Response to CSII Catheters in a Tummy Tuck Model</brief_title>
  <acronym>IRCATT</acronym>
  <official_title>A Pilot Study for the Systematic Evaluation of the Inflammatory Response to Commercially Available Insulin Infusion Catheters in Subcutaneous Adipose Tissue</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical University of Graz</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Medical University of Graz</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>
      In insulin pump therapy, insulin is continuously infused into the subcutaneous adipose tissue&#xD;
      via a continuous subcutaneous insulin infusion (CSII) catheter using a basal/bolus pattern.&#xD;
      Unfortunately, insulin absorption from the tissue surrounding a CSII catheter can be slow,&#xD;
      variable, and unreliable. It is recommended to replace CSII catheters after 2 to 3 days of&#xD;
      use. Frequently changing the injection site can be tedious and moreover leads to scarring,&#xD;
      while reusing the same injection site can lead to medical complications such as&#xD;
      lipohypertrophy. CSII catheters are manufactured from both steel and Teflon and use of either&#xD;
      of these materials is based on personal preference/experience rather than scientific,&#xD;
      empirical data. We hypothesize that the inflammatory response to CSII catheters is a major&#xD;
      contributor to variable insulin absorption and that this response is significantly different&#xD;
      between materials and catheters shapes. In order to develop CSII catheters with an extended&#xD;
      life-time up to 7 days, we need to better understand the inflammatory response caused by the&#xD;
      introduction and maintenance of a CSII catheter into the subcutaneous adipose tissue. This&#xD;
      study is a pilot study in humans scheduled for elective plastic surgery where a large skin&#xD;
      flap is removed from the abdominal region. Teflon and steel CSII catheters will be inserted&#xD;
      into the abdomen 7, 4, and 3 days prior to surgery. This study design allows for the removal&#xD;
      of tissue plugs surrounding CSII catheters without causing additional scarring for the&#xD;
      patient.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background:&#xD;
&#xD;
      Approximately one million patients worldwide manage their diabetes with an insulin pump.&#xD;
      Insulin is continuously infused into the subcutaneous adipose tissue via a Continuous&#xD;
      Subcutaneous Insulin Infusion (CSII) catheter using a basal/bolus pattern that can be&#xD;
      adjusted by the patient according to meal times, mimicking the natural function of the&#xD;
      pancreas. One major advantage of this form of therapy is the improvement of living quality.&#xD;
      Compared to multiple daily insulin injections, the catheter has to be inserted only once&#xD;
      every 2-3 days where it remains within the subcutaneous tissue. This is especially&#xD;
      advantageous for children of young age.&#xD;
&#xD;
      Unfortunately, insulin absorption from the tissue surrounding a CSII catheter can be slow,&#xD;
      variable, and unreliable. It is recommended to replace infusion sets and CSII catheters after&#xD;
      2 to 3 days of clinical use. After this time, blood glucose control becomes difficult for the&#xD;
      patient because insulin absorption from the subcutaneous tissue into the blood stream and&#xD;
      lymphatics becomes highly variable.&#xD;
&#xD;
      The underlying mechanisms for impaired insulin absorption are poorly understood and the&#xD;
      knowledge of rotating the site of injection is based on user experience. Frequently changing&#xD;
      the injection site can be tedious and moreover leads to scarring, while reusing the same&#xD;
      injection site can lead to medical complications such as lipohypertrophy. In order to develop&#xD;
      CSII catheters with an extended life-time up to 7 days, there is a need to better understand&#xD;
      the inflammatory response caused by the introduction and maintenance of a CSII catheter into&#xD;
      the subcutaneous adipose tissue. The clinical use of a 7-day CSII catheter with low&#xD;
      pharmacokinetics (PK) variability will significantly improve blood glucose control, decrease&#xD;
      the risk for hypoglycemia, increase compliance, and decrease cost. Since continuous glucose&#xD;
      monitoring (CGM) devices are approved for 7-day wear time, the development of a CSII catheter&#xD;
      with extended lifetime is also crucial for the development of single-port artificial pancreas&#xD;
      (AP) systems where CSII and CGM are combined in one catheter, mimicking pancreatic function.&#xD;
      Furthermore, the improvement of catheter longevity will reduce insertion sites and scars.&#xD;
      This is especially important for children with a smaller body surface area.&#xD;
&#xD;
      The choice of one material over the other is largely based on the patient's personal&#xD;
      preference, his or her endocrinologist's or diabetes educator's opinion and therapy costs.&#xD;
      There is a trend in both the United States and Europe towards using Teflon sets (90 % and 75&#xD;
      %, respectively) but approximately 40 to 45 % of pump users in Germany use steel catheters.&#xD;
      Compared to Teflon, steel catheters are easier to insert and are less prone to kinking, and&#xD;
      can be worn by patients allergic to Teflon. Patients using steel catheters report better&#xD;
      metabolic control, less variable insulin absorption and less unexplained hyperglycemia&#xD;
      (Heinemann 2016; Reichert et al. 2013). However, especially during exercise, steel may cause&#xD;
      discomfort and the softer and more flexible Teflon catheter is assumed to be more comfortable&#xD;
      to wear. The wear-time of the CSII catheter considerably varies between patients (from 2 to&#xD;
      10 days), although recommendations for the optimal frequency of changing an insulin infusion&#xD;
      set (2 days for steel and 3 days for Teflon) exist.&#xD;
&#xD;
      In a prior pig study the inflammatory response to commercial CSII catheters comparing steel,&#xD;
      Teflon and Teflon with an anti-inflammatory coating was analyzed. There was significant&#xD;
      reduction in area of inflammation and macrophage recruitment around the non-coated and coated&#xD;
      Teflon catheters. Steel elicited the most severe inflammatory response with significantly&#xD;
      higher fibrosis.&#xD;
&#xD;
      Although the pig has proven to be an excellent model for the study of human skin and adipose&#xD;
      tissue, there is an urgent medical need to confirm these findings in a human model. For the&#xD;
      histopathological and molecular analysis of subcutaneous tissue in the vicinity of the&#xD;
      catheter, large amounts of tissue need to be excised from the site of interest. This makes a&#xD;
      human study almost impossible. Nevertheless, the generation of human data is crucial and a&#xD;
      lot of this important information is still lacking in diabetes research and treatment. The&#xD;
      possibility to excise extensive amounts of tissue without causing additional scars or pain&#xD;
      (except that caused by the abdominoplasty itself) for the patient presents the main benefit&#xD;
      of this study setup.&#xD;
&#xD;
      Aim:&#xD;
&#xD;
      The aim of this study is to compare the inflammatory response to commercially available CSII&#xD;
      catheters of two different materials (steel and Teflon) over 1 day, 4 days and 7 days of&#xD;
      wear-time in humans scheduled for elective plastic surgery (abdominoplasty).&#xD;
&#xD;
      Hypothesis:&#xD;
&#xD;
      Conventional steel CSII catheters elicit a more severe acute inflammatory response in the&#xD;
      subcutaneous adipose tissue than Teflon CSII catheters.&#xD;
&#xD;
      H0 = there is no difference in mean area of fibrin deposition around catheters H1 = there is&#xD;
      a significant difference in mean area of fibrin deposition between catheters&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">February 1, 2018</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">May 31, 2023</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Non-diabetic patients scheduled for selective plastic surgery (abdominoplasty).</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>The only person blinded in this study is the pathologist analyzing the tissue sections.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Area of inflammation (mm2)</measure>
    <time_frame>7 days</time_frame>
    <description>Assessed by microscopy; area of inflamed tissue, including cell infiltration, necrosis, fibrin/collagen deposition</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Area of fibrin deposition (mm2)</measure>
    <time_frame>7 days</time_frame>
    <description>Assessed by microscopy; area of fibrin</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area of fat necrosis (mm2)</measure>
    <time_frame>7 days</time_frame>
    <description>assessed by microscopy; area of necrosed adipocytes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Inflammation distance (mm)</measure>
    <time_frame>7 days</time_frame>
    <description>assessed by microscopy; distance from skin surface to lowest point of microscopically assessed inflammation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cytokine gene expression (fold change)</measure>
    <time_frame>7 days</time_frame>
    <description>Assessed by qPCR; relative fold change in gene expression compared to non-traumatized tissue (IL-1b, TNFa, TGFb, IL-6, IL-8, IL-10)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Macrophage marker gene expression (fold change)</measure>
    <time_frame>7 days</time_frame>
    <description>Assessed by qPCR; relative fold change in CD68 gene expression compared to non-traumatized tissue</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Diabetes Mellitus</condition>
  <arm_group>
    <arm_group_label>Insertion of Insulin Infusion Catheters</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Non-diabetic patients scheduled for abdominoplasty will be inserted continuous subcutaneous insulin infusion (CSII) catheters of two different materials into the part of the abdomen which will be removed during surgery.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Continous Subcutaneous Insulin Infusion Catheter</intervention_name>
    <description>Catheters will be inserted into the abdomen of each patient using aseptic technique according to the following schedule: (1) 8 days before surgery, (2) 4 days before surgery and (3) 1 day before surgery (Table 1). At each time point 2 steel (Medtronic Sure-T, 9 mm) and 2 Teflon (Medtronic Quick-set®, 9 mm) CSII catheters will be inserted into the subcutaneous abdominal tissue. In total, 12 catheters will be inserted into each patient's abdomen using only the area predefined by the plastic surgeon for removal.</description>
    <arm_group_label>Insertion of Insulin Infusion Catheters</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Men and women, age 18 years or older&#xD;
&#xD;
          -  Scheduled elective abdominoplasty at the Dpt. of Plastic Surgery, Medical University&#xD;
             of Graz&#xD;
&#xD;
          -  Signed informed consent form&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Allergy to Teflon or steel&#xD;
&#xD;
          -  Known skin diseases (atopic dermatitis, psoriasis)&#xD;
&#xD;
          -  History of immunodeficiency diseases&#xD;
&#xD;
          -  Patients on glucocorticoid or other immunomodulating therapy&#xD;
&#xD;
          -  History of bleeding disorder&#xD;
&#xD;
          -  Pregnancy or planned pregnancy&#xD;
&#xD;
          -  Unable to fully understand study procedures and to provide informed consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Lars-Peter Kamolz, MD Prof</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medical University of Graz</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jasmin R Hauzenberger, MSc</last_name>
    <phone>+436645172277</phone>
    <email>jasmin.hauzenberger@medunigraz.at</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Julia K Mader, MD Prof</last_name>
    <phone>+43316385</phone>
    <phone_ext>80253</phone_ext>
    <email>julia.mader@medunigraz.at</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Division of Plastic, Aesthetic and Reconstructive Surgery</name>
      <address>
        <city>Graz</city>
        <zip>8036</zip>
        <country>Austria</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Birgit Michelitsch, BSc</last_name>
      <phone>+43316385</phone>
      <phone_ext>30357</phone_ext>
      <email>birgit.michelitsch@medunigraz.at</email>
    </contact>
    <contact_backup>
      <last_name>Alexandru Tuca, MD</last_name>
      <phone>+43316385</phone>
      <phone_ext>30742</phone_ext>
      <email>alexandru.tuca@medunigraz.at</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Austria</country>
  </location_countries>
  <reference>
    <citation>Conwell LS, Pope E, Artiles AM, Mohanta A, Daneman A, Daneman D. Dermatological complications of continuous subcutaneous insulin infusion in children and adolescents. J Pediatr. 2008 May;152(5):622-8. doi: 10.1016/j.jpeds.2007.10.006. Epub 2008 Jan 22.</citation>
    <PMID>18410763</PMID>
  </reference>
  <reference>
    <citation>Deiss D, Adolfsson P, Alkemade-van Zomeren M, Bolli GB, Charpentier G, Cobelli C, Danne T, Girelli A, Mueller H, Verderese CA, Renard E. Insulin Infusion Set Use: European Perspectives and Recommendations. Diabetes Technol Ther. 2016 Sep;18(9):517-24. doi: 10.1089/dia.2016.07281.sf. Epub 2016 Aug 15.</citation>
    <PMID>27526329</PMID>
  </reference>
  <reference>
    <citation>Facchinetti A, Sparacino G, Guerra S, Luijf YM, DeVries JH, Mader JK, Ellmerer M, Benesch C, Heinemann L, Bruttomesso D, Avogaro A, Cobelli C; AP@home Consortium. Real-time improvement of continuous glucose monitoring accuracy: the smart sensor concept. Diabetes Care. 2013 Apr;36(4):793-800. doi: 10.2337/dc12-0736. Epub 2012 Nov 19.</citation>
    <PMID>23172973</PMID>
  </reference>
  <reference>
    <citation>Heinemann L. Insulin Infusion Sets: A Critical Reappraisal. Diabetes Technol Ther. 2016 May;18(5):327-33. doi: 10.1089/dia.2016.0013. Epub 2016 Feb 17.</citation>
    <PMID>26885764</PMID>
  </reference>
  <reference>
    <citation>Heinemann L, Fleming GA, Petrie JR, Holl RW, Bergenstal RM, Peters AL. Insulin pump risks and benefits: a clinical appraisal of pump safety standards, adverse event reporting, and research needs: a joint statement of the European Association for the Study of Diabetes and the American Diabetes Association Diabetes Technology Working Group. Diabetes Care. 2015 Apr;38(4):716-22. doi: 10.2337/dc15-0168.</citation>
    <PMID>25776138</PMID>
  </reference>
  <reference>
    <citation>Heinemann L. Variability of insulin absorption and insulin action. Diabetes Technol Ther. 2002;4(5):673-82. doi: 10.1089/152091502320798312.</citation>
    <PMID>12450450</PMID>
  </reference>
  <reference>
    <citation>Heinemann L, Krinelke L. Insulin infusion set: the Achilles heel of continuous subcutaneous insulin infusion. J Diabetes Sci Technol. 2012 Jul 1;6(4):954-64. doi: 10.1177/193229681200600429.</citation>
    <PMID>22920824</PMID>
  </reference>
  <reference>
    <citation>Heinemann L, Walsh J, Roberts R. We Need More Research and Better Designs for Insulin Infusion Sets. J Diabetes Sci Technol. 2014 Mar;8(2):199-202. doi: 10.1177/1932296814523882. Epub 2014 Feb 27. No abstract available.</citation>
    <PMID>24876567</PMID>
  </reference>
  <reference>
    <citation>Macmillan K, Bruera E, Kuehn N, Selmser P, Macmillan A. A prospective comparison study between a butterfly needle and a Teflon cannula for subcutaneous narcotic administration. J Pain Symptom Manage. 1994 Feb;9(2):82-4. doi: 10.1016/0885-3924(94)90160-0.</citation>
    <PMID>8021539</PMID>
  </reference>
  <reference>
    <citation>Pickup JC, Yemane N, Brackenridge A, Pender S. Nonmetabolic complications of continuous subcutaneous insulin infusion: a patient survey. Diabetes Technol Ther. 2014 Mar;16(3):145-9. doi: 10.1089/dia.2013.0192. Epub 2013 Nov 1.</citation>
    <PMID>24180294</PMID>
  </reference>
  <reference>
    <citation>Reichert, D. et al., 2013. Realität der Insulinpumpentherapie in Diabetesschwerpunktpraxen: Daten von 1142 Patienten aus 40 diabetologischen Schwerpunktpraxen. Diabetes Stoffwechsel Herz, 22, pp.367-375.</citation>
  </reference>
  <reference>
    <citation>Sampson Perrin AJ, Guzzetta RC, Miller KM, Foster NC, Lee A, Lee JM, Block JM, Beck RW; T1D Exchange Clinic Network. A web-based study of the relationship of duration of insulin pump infusion set use and fasting blood glucose level in adults with type 1 diabetes. Diabetes Technol Ther. 2015 May;17(5):307-10. doi: 10.1089/dia.2014.0336. Epub 2015 Jan 26.</citation>
    <PMID>25622214</PMID>
  </reference>
  <reference>
    <citation>Schmid V, Hohberg C, Borchert M, Forst T, Pfutzner A. Pilot study for assessment of optimal frequency for changing catheters in insulin pump therapy-trouble starts on day 3. J Diabetes Sci Technol. 2010 Jul 1;4(4):976-82. doi: 10.1177/193229681000400429.</citation>
    <PMID>20663464</PMID>
  </reference>
  <reference>
    <citation>Sullivan TP, Eaglstein WH, Davis SC, Mertz P. The pig as a model for human wound healing. Wound Repair Regen. 2001 Mar-Apr;9(2):66-76. doi: 10.1046/j.1524-475x.2001.00066.x.</citation>
    <PMID>11350644</PMID>
  </reference>
  <reference>
    <citation>Walsh J, Roberts R, Weber D, Faber-Heinemann G, Heinemann L. Insulin Pump and CGM Usage in the United States and Germany: Results of a Real-World Survey With 985 Subjects. J Diabetes Sci Technol. 2015 Jun 12;9(5):1103-10. doi: 10.1177/1932296815588945.</citation>
    <PMID>26071425</PMID>
  </reference>
  <verification_date>November 2022</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">October 2, 2017</study_first_posted>
  <last_update_submitted>November 2, 2022</last_update_submitted>
  <last_update_submitted_qc>November 2, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 4, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Diabetes Mellitus</keyword>
  <keyword>Insulin Pump Therapy</keyword>
  <keyword>Continuous Subcutaneous Insulin Infusion</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Insulin</mesh_term>
  </intervention_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/NCT03298295
org study id: IRCATT
nct id: NCT03298295
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
In insulin pump therapy, insulin is continuously infused into the subcutaneous adipose tissue
      via a continuous subcutaneous insulin infusion (CSII) catheter using a basal/bolus pattern.
      Unfortunately, insulin absorption from the tissue surrounding a CSII catheter can be slow,
      variable, and unreliable. It is recommended to replace CSII catheters after 2 to 3 days of
      use. Frequently changing the injection site can be tedious and moreover leads to scarring,
      while reusing the same injection site can lead to medical complications such as
      lipohypertrophy. CSII catheters are manufactured from both steel and Teflon and use of either
      of these materials is based on personal preference/experience rather than scientific,
      empirical data. We hypothesize that the inflammatory response to CSII catheters is a major
      contributor to variable insulin absorption and that this response is significantly different
      between materials and catheters shapes. In order to develop CSII catheters with an extended
      life-time up to 7 days, we need to better understand the inflammatory response caused by the
      introduction and maintenance of a CSII catheter into the subcutaneous adipose tissue. This
      study is a pilot study in humans scheduled for elective plastic surgery where a large skin
      flap is removed from the abdominal region. Teflon and steel CSII catheters will be inserted
      into the abdomen 7, 4, and 3 days prior to surgery. This study design allows for the removal
      of tissue plugs surrounding CSII catheters without causing additional scarring for the
      patient.
Background:

      Approximately one million patients worldwide manage their diabetes with an insulin pump.
      Insulin is continuously infused into the subcutaneous adipose tissue via a Continuous
      Subcutaneous Insulin Infusion (CSII) catheter using a basal/bolus pattern that can be
      adjusted by the patient according to meal times, mimicking the natural function of the
      pancreas. One major advantage of this form of therapy is the improvement of living quality.
      Compared to multiple daily insulin injections, the catheter has to be inserted only once
      every 2-3 days where it remains within the subcutaneous tissue. This is especially
      advantageous for children of young age.

      Unfortunately, insulin absorption from the tissue surrounding a CSII catheter can be slow,
      variable, and unreliable. It is recommended to replace infusion sets and CSII catheters after
      2 to 3 days of clinical use. After this time, blood glucose control becomes difficult for the
      patient because insulin absorption from the subcutaneous tissue into the blood stream and
      lymphatics becomes highly variable.

      The underlying mechanisms for impaired insulin absorption are poorly understood and the
      knowledge of rotating the site of injection is based on user experience. Frequently changing
      the injection site can be tedious and moreover leads to scarring, while reusing the same
      injection site can lead to medical complications such as lipohypertrophy. In order to develop
      CSII catheters with an extended life-time up to 7 days, there is a need to better understand
      the inflammatory response caused by the introduction and maintenance of a CSII catheter into
      the subcutaneous adipose tissue. The clinical use of a 7-day CSII catheter with low
      pharmacokinetics (PK) variability will significantly improve blood glucose control, decrease
      the risk for hypoglycemia, increase compliance, and decrease cost. Since continuous glucose
      monitoring (CGM) devices are approved for 7-day wear time, the development of a CSII catheter
      with extended lifetime is also crucial for the development of single-port artificial pancreas
      (AP) systems where CSII and CGM are combined in one catheter, mimicking pancreatic function.
      Furthermore, the improvement of catheter longevity will reduce insertion sites and scars.
      This is especially important for children with a smaller body surface area.

      The choice of one material over the other is largely based on the patient's personal
      preference, his or her endocrinologist's or diabetes educator's opinion and therapy costs.
      There is a trend in both the United States and Europe towards using Teflon sets (90 % and 75
      %, respectively) but approximately 40 to 45 % of pump users in Germany use steel catheters.
      Compared to Teflon, steel catheters are easier to insert and are less prone to kinking, and
      can be worn by patients allergic to Teflon. Patients using steel catheters report better
      metabolic control, less variable insulin absorption and less unexplained hyperglycemia
      (Heinemann 2016; Reichert et al. 2013). However, especially during exercise, steel may cause
      discomfort and the softer and more flexible Teflon catheter is assumed to be more comfortable
      to wear. The wear-time of the CSII catheter considerably varies between patients (from 2 to
      10 days), although recommendations for the optimal frequency of changing an insulin infusion
      set (2 days for steel and 3 days for Teflon) exist.

      In a prior pig study the inflammatory response to commercial CSII catheters comparing steel,
      Teflon and Teflon with an anti-inflammatory coating was analyzed. There was significant
      reduction in area of inflammation and macrophage recruitment around the non-coated and coated
      Teflon catheters. Steel elicited the most severe inflammatory response with significantly
      higher fibrosis.

      Although the pig has proven to be an excellent model for the study of human skin and adipose
      tissue, there is an urgent medical need to confirm these findings in a human model. For the
      histopathological and molecular analysis of subcutaneous tissue in the vicinity of the
      catheter, large amounts of tissue need to be excised from the site of interest. This makes a
      human study almost impossible. Nevertheless, the generation of human data is crucial and a
      lot of this important information is still lacking in diabetes research and treatment. The
      possibility to excise extensive amounts of tissue without causing additional scars or pain
      (except that caused by the abdominoplasty itself) for the patient presents the main benefit
      of this study setup.

      Aim:

      The aim of this study is to compare the inflammatory response to commercially available CSII
      catheters of two different materials (steel and Teflon) over 1 day, 4 days and 7 days of
      wear-time in humans scheduled for elective plastic surgery (abdominoplasty).

      Hypothesis:

      Conventional steel CSII catheters elicit a more severe acute inflammatory response in the
      subcutaneous adipose tissue than Teflon CSII catheters.

      H0 = there is no difference in mean area of fibrin deposition around catheters H1 = there is
      a significant difference in mean area of fibrin deposition between catheters
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Non-diabetic patients scheduled for selective plastic surgery (abdominoplasty).
primary purpose: Basic Science
masking: None (Open Label)
masking description: The only person blinded in this study is the pathologist analyzing the tissue sections.
measure: Area of inflammation (mm2)
time frame: 7 days
description: Assessed by microscopy; area of inflamed tissue, including cell infiltration, necrosis, fibrin/collagen deposition
measure: Area of fibrin deposition (mm2)
time frame: 7 days
description: Assessed by microscopy; area of fibrin
measure: Area of fat necrosis (mm2)
time frame: 7 days
description: assessed by microscopy; area of necrosed adipocytes
measure: Inflammation distance (mm)
time frame: 7 days
description: assessed by microscopy; distance from skin surface to lowest point of microscopically assessed inflammation
measure: Cytokine gene expression (fold change)
time frame: 7 days
description: Assessed by qPCR; relative fold change in gene expression compared to non-traumatized tissue (IL-1b, TNFa, TGFb, IL-6, IL-8, IL-10)
measure: Macrophage marker gene expression (fold change)
time frame: 7 days
description: Assessed by qPCR; relative fold change in CD68 gene expression compared to non-traumatized tissue
arm group label: Insertion of Insulin Infusion Catheters
arm group type: Experimental
description: Non-diabetic patients scheduled for abdominoplasty will be inserted continuous subcutaneous insulin infusion (CSII) catheters of two different materials into the part of the abdomen which will be removed during surgery.
intervention type: Device
intervention name: Continous Subcutaneous Insulin Infusion Catheter
description: Catheters will be inserted into the abdomen of each patient using aseptic technique according to the following schedule: (1) 8 days before surgery, (2) 4 days before surgery and (3) 1 day before surgery (Table 1). At each time point 2 steel (Medtronic Sure-T, 9 mm) and 2 Teflon (Medtronic Quick-set®, 9 mm) CSII catheters will be inserted into the subcutaneous abdominal tissue. In total, 12 catheters will be inserted into each patient's abdomen using only the area predefined by the plastic surgeon for removal.
arm group label: Insertion of Insulin Infusion Catheters
criteria: 
gender: All
minimum age: 18 Years
maximum age: 99 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Lars-Peter Kamolz, MD Prof
role: Principal Investigator
affiliation: Medical University of Graz
last name: Jasmin R Hauzenberger, MSc
phone: +436645172277
email: jasmin.hauzenberger@medunigraz.at
last name: Julia K Mader, MD Prof
phone: +43316385
phone ext: 80253
email: julia.mader@medunigraz.at
facility: 
status: Recruiting
contact: 
contact backup: 
country: Austria
citation: Conwell LS, Pope E, Artiles AM, Mohanta A, Daneman A, Daneman D. Dermatological complications of continuous subcutaneous insulin infusion in children and adolescents. J Pediatr. 2008 May;152(5):622-8. doi: 10.1016/j.jpeds.2007.10.006. Epub 2008 Jan 22.
PMID: 18410763
citation: Deiss D, Adolfsson P, Alkemade-van Zomeren M, Bolli GB, Charpentier G, Cobelli C, Danne T, Girelli A, Mueller H, Verderese CA, Renard E. Insulin Infusion Set Use: European Perspectives and Recommendations. Diabetes Technol Ther. 2016 Sep;18(9):517-24. doi: 10.1089/dia.2016.07281.sf. Epub 2016 Aug 15.
PMID: 27526329
citation: Facchinetti A, Sparacino G, Guerra S, Luijf YM, DeVries JH, Mader JK, Ellmerer M, Benesch C, Heinemann L, Bruttomesso D, Avogaro A, Cobelli C; AP@home Consortium. Real-time improvement of continuous glucose monitoring accuracy: the smart sensor concept. Diabetes Care. 2013 Apr;36(4):793-800. doi: 10.2337/dc12-0736. Epub 2012 Nov 19.
PMID: 23172973
citation: Heinemann L. Insulin Infusion Sets: A Critical Reappraisal. Diabetes Technol Ther. 2016 May;18(5):327-33. doi: 10.1089/dia.2016.0013. Epub 2016 Feb 17.
PMID: 26885764
citation: Heinemann L, Fleming GA, Petrie JR, Holl RW, Bergenstal RM, Peters AL. Insulin pump risks and benefits: a clinical appraisal of pump safety standards, adverse event reporting, and research needs: a joint statement of the European Association for the Study of Diabetes and the American Diabetes Association Diabetes Technology Working Group. Diabetes Care. 2015 Apr;38(4):716-22. doi: 10.2337/dc15-0168.
PMID: 25776138
citation: Heinemann L. Variability of insulin absorption and insulin action. Diabetes Technol Ther. 2002;4(5):673-82. doi: 10.1089/152091502320798312.
PMID: 12450450
citation: Heinemann L, Krinelke L. Insulin infusion set: the Achilles heel of continuous subcutaneous insulin infusion. J Diabetes Sci Technol. 2012 Jul 1;6(4):954-64. doi: 10.1177/193229681200600429.
PMID: 22920824
citation: Heinemann L, Walsh J, Roberts R. We Need More Research and Better Designs for Insulin Infusion Sets. J Diabetes Sci Technol. 2014 Mar;8(2):199-202. doi: 10.1177/1932296814523882. Epub 2014 Feb 27. No abstract available.
PMID: 24876567
citation: Macmillan K, Bruera E, Kuehn N, Selmser P, Macmillan A. A prospective comparison study between a butterfly needle and a Teflon cannula for subcutaneous narcotic administration. J Pain Symptom Manage. 1994 Feb;9(2):82-4. doi: 10.1016/0885-3924(94)90160-0.
PMID: 8021539
citation: Pickup JC, Yemane N, Brackenridge A, Pender S. Nonmetabolic complications of continuous subcutaneous insulin infusion: a patient survey. Diabetes Technol Ther. 2014 Mar;16(3):145-9. doi: 10.1089/dia.2013.0192. Epub 2013 Nov 1.
PMID: 24180294
citation: Reichert, D. et al., 2013. Realität der Insulinpumpentherapie in Diabetesschwerpunktpraxen: Daten von 1142 Patienten aus 40 diabetologischen Schwerpunktpraxen. Diabetes Stoffwechsel Herz, 22, pp.367-375.
citation: Sampson Perrin AJ, Guzzetta RC, Miller KM, Foster NC, Lee A, Lee JM, Block JM, Beck RW; T1D Exchange Clinic Network. A web-based study of the relationship of duration of insulin pump infusion set use and fasting blood glucose level in adults with type 1 diabetes. Diabetes Technol Ther. 2015 May;17(5):307-10. doi: 10.1089/dia.2014.0336. Epub 2015 Jan 26.
PMID: 25622214
citation: Schmid V, Hohberg C, Borchert M, Forst T, Pfutzner A. Pilot study for assessment of optimal frequency for changing catheters in insulin pump therapy-trouble starts on day 3. J Diabetes Sci Technol. 2010 Jul 1;4(4):976-82. doi: 10.1177/193229681000400429.
PMID: 20663464
citation: Sullivan TP, Eaglstein WH, Davis SC, Mertz P. The pig as a model for human wound healing. Wound Repair Regen. 2001 Mar-Apr;9(2):66-76. doi: 10.1046/j.1524-475x.2001.00066.x.
PMID: 11350644
citation: Walsh J, Roberts R, Weber D, Faber-Heinemann G, Heinemann L. Insulin Pump and CGM Usage in the United States and Germany: Results of a Real-World Survey With 985 Subjects. J Diabetes Sci Technol. 2015 Jun 12;9(5):1103-10. doi: 10.1177/1932296815588945.
PMID: 26071425
responsible party type: Sponsor
mesh term: Diabetes Mellitus
mesh term: Insulin
sharing ipd: Undecided