<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/NCT03229850</url>
  </required_header>
  <id_info>
    <org_study_id>H17-01270</org_study_id>
    <nct_id>NCT03229850</nct_id>
  </id_info>
  <brief_title>Dynamics of Insulin Absorption in Subclinical Lipohypertrophy Using the Euglycemic Clamp Technique</brief_title>
  <official_title>Dynamics of Insulin Absorption in Subclinical Lipohypertrophy Using the Euglycemic Clamp Technique</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Graydon Meneilly</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of British Columbia</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>
      This study will use the euglycemic clamp technique to evaluate insulin absorption when&#xD;
      insulin is administered subcutaneously in an area of subclinical lipohypertrophy vs an area&#xD;
      of normal tissue.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The use of insulin to manage diabetes can cause changes to the skin at sites where insulin is&#xD;
      administered. These changes may be felt as lumps under the skin. Insulin injected into these&#xD;
      areas may not work as well leading to needing increasing doses of insulin to control blood&#xD;
      glucose levels. Hypoglycemia can occur when insulin is injected into normal areas. Previous&#xD;
      studies have found that these lipohypertrophic areas can be seen on ultrasound before they&#xD;
      can be felt. The Investigators will be using the euglycemic clamp techique to evaluate&#xD;
      insulin absorption to see whether tissue with lumps that cannot be felt but are seen on&#xD;
      ultrasound affect how insulin is absorbed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Suspended</overall_status>
  <why_stopped>
    Study was suspended due to current COVID 19 research curtailment&#xD;
  </why_stopped>
  <start_date type="Actual">February 1, 2021</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">December 2023</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Investigator, Outcomes Assessor)</masking>
    <masking_description>During one euglycemic clamp study, insulin lispro will be injected subcutaneously into an area of subclinical lipohypertrophy of the abdomen identified by ultrasound, during the other insulin lispro will be injected to an area with no subclinical lipohypertrophy.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Insulin Levels</measure>
    <time_frame>2 months</time_frame>
    <description>The euglycemic clamp technique will be used. Insulin levels will be analyzed by Eliza assay</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">10</enrollment>
  <condition>Diabetes Mellitus</condition>
  <condition>Lipohypertrophy</condition>
  <arm_group>
    <arm_group_label>Subclinical Lipohypertrophy</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Insulin lispro will be injected in the abdomen into an area of subclinical lipohypertrophy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>No Subclinical Lipohypertrophy</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Insulin lispro will be injected in the abdomen into an area where there is no subclinical lipohypertrophy.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Insulin lispro</intervention_name>
    <description>Insulin lispro will be injected into the abdomen into an area of subclinical lipohypertrophy or an area with no subclinical lipohypertrophy</description>
    <arm_group_label>No Subclinical Lipohypertrophy</arm_group_label>
    <arm_group_label>Subclinical Lipohypertrophy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participated in Glycemic Variability study&#xD;
&#xD;
          -  Type 2 Diabetes for at least 2 years&#xD;
&#xD;
          -  Currently using insulin to manage diabetes&#xD;
&#xD;
          -  Have used insulin to manage diabetes for at least 2 years&#xD;
&#xD;
          -  Age 19 or older&#xD;
&#xD;
          -  BMI &lt; 30 kg/m2&#xD;
&#xD;
          -  Confirmed areas of subclinical lipohypertrophic adipose tissue lesions via ultrasound&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Taking other injectable medications (eg liraglutide/Victoza&#xD;
&#xD;
          -  Taking systemic steroids (ie prednisone)&#xD;
&#xD;
          -  Severe renal insufficiency (eGFR &lt; 30 ml/min/1.73 m2&#xD;
&#xD;
          -  Hypoglycemic unawareness&#xD;
&#xD;
          -  Current pregnancy&#xD;
&#xD;
          -  Not fluent in speaking and writing English (unless accompanied by a translator)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Graydon Meneilly, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of British Columbia</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of British Columbia - Gerontology Research Lab</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <zip>V5Z 1M9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <reference>
    <citation>Fujikura J, Fujimoto M, Yasue S, Noguchi M, Masuzaki H, Hosoda K, Tachibana T, Sugihara H, Nakao K. Insulin-induced lipohypertrophy: report of a case with histopathology. Endocr J. 2005 Oct;52(5):623-8. doi: 10.1507/endocrj.52.623.</citation>
    <PMID>16284443</PMID>
  </reference>
  <reference>
    <citation>Raile K, Noelle V, Landgraf R, Schwarz HP. Insulin antibodies are associated with lipoatrophy but also with lipohypertrophy in children and adolescents with type 1 diabetes. Exp Clin Endocrinol Diabetes. 2001;109(8):393-6. doi: 10.1055/s-2001-18991.</citation>
    <PMID>11748486</PMID>
  </reference>
  <reference>
    <citation>Schiazza L, Occella C, Bleidl D, Rampini E. Insulin lipohypertrophy. J Am Acad Dermatol. 1990 Jan;22(1):148-9. doi: 10.1016/s0190-9622(08)80037-0. No abstract available.</citation>
    <PMID>2076114</PMID>
  </reference>
  <reference>
    <citation>Vardar B, Kizilci S. Incidence of lipohypertrophy in diabetic patients and a study of influencing factors. Diabetes Res Clin Pract. 2007 Aug;77(2):231-6. doi: 10.1016/j.diabres.2006.12.023. Epub 2007 Feb 15.</citation>
    <PMID>17303282</PMID>
  </reference>
  <reference>
    <citation>Young RJ, Hannan WJ, Frier BM, Steel JM, Duncan LJ. Diabetic lipohypertrophy delays insulin absorption. Diabetes Care. 1984 Sep-Oct;7(5):479-80. doi: 10.2337/diacare.7.5.479.</citation>
    <PMID>6389062</PMID>
  </reference>
  <reference>
    <citation>Chowdhury TA, Escudier V. Poor glycaemic control caused by insulin induced lipohypertrophy. BMJ. 2003 Aug 16;327(7411):383-4. doi: 10.1136/bmj.327.7411.383. No abstract available.</citation>
    <PMID>12919996</PMID>
  </reference>
  <reference>
    <citation>Hauner H, Stockamp B, Haastert B. Prevalence of lipohypertrophy in insulin-treated diabetic patients and predisposing factors. Exp Clin Endocrinol Diabetes. 1996;104(2):106-10. doi: 10.1055/s-0029-1211431.</citation>
    <PMID>8740933</PMID>
  </reference>
  <reference>
    <citation>Blanco M, Hernandez MT, Strauss KW, Amaya M. Prevalence and risk factors of lipohypertrophy in insulin-injecting patients with diabetes. Diabetes Metab. 2013 Oct;39(5):445-53. doi: 10.1016/j.diabet.2013.05.006. Epub 2013 Jul 22.</citation>
    <PMID>23886784</PMID>
  </reference>
  <reference>
    <citation>Thow JC, Johnson AB, Marsden S, Taylor R, Home PD. Morphology of palpably abnormal injection sites and effects on absorption of isophane(NPH) insulin. Diabet Med. 1990 Nov;7(9):795-9. doi: 10.1111/j.1464-5491.1990.tb01494.x.</citation>
    <PMID>2148131</PMID>
  </reference>
  <reference>
    <citation>Overland J, Molyneaux L, Tewari S, Fatouros R, Melville P, Foote D, Wu T, Yue DK. Lipohypertrophy: does it matter in daily life? A study using a continuous glucose monitoring system. Diabetes Obes Metab. 2009 May;11(5):460-3. doi: 10.1111/j.1463-1326.2008.00972.x. Epub 2009 Feb 19.</citation>
    <PMID>19236441</PMID>
  </reference>
  <reference>
    <citation>Heinemann L, Weyer C, Rauhaus M, Heinrichs S, Heise T. Variability of the metabolic effect of soluble insulin and the rapid-acting insulin analog insulin aspart. Diabetes Care. 1998 Nov;21(11):1910-4. doi: 10.2337/diacare.21.11.1910.</citation>
    <PMID>9802742</PMID>
  </reference>
  <reference>
    <citation>Famulla S, Hovelmann U, Fischer A, Coester HV, Hermanski L, Kaltheuner M, Kaltheuner L, Heinemann L, Heise T, Hirsch L. Insulin Injection Into Lipohypertrophic Tissue: Blunted and More Variable Insulin Absorption and Action and Impaired Postprandial Glucose Control. Diabetes Care. 2016 Sep;39(9):1486-92. doi: 10.2337/dc16-0610. Epub 2016 Jul 13.</citation>
    <PMID>27411698</PMID>
  </reference>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>June 26, 2017</study_first_submitted>
  <study_first_submitted_qc>July 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 26, 2017</study_first_posted>
  <last_update_submitted>May 8, 2023</last_update_submitted>
  <last_update_submitted_qc>May 8, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 10, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of British Columbia</investigator_affiliation>
    <investigator_full_name>Graydon Meneilly</investigator_full_name>
    <investigator_title>Professor, UBC Department of Medicine</investigator_title>
  </responsible_party>
  <keyword>Diabetes</keyword>
  <keyword>Insulin</keyword>
  <keyword>Lipohypertrophy</keyword>
  <keyword>Euglycemic Clamp</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Insulin Lispro</mesh_term>
  </intervention_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/NCT03229850
org study id: H17-01270
nct id: NCT03229850
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study will use the euglycemic clamp technique to evaluate insulin absorption when
      insulin is administered subcutaneously in an area of subclinical lipohypertrophy vs an area
      of normal tissue.
The use of insulin to manage diabetes can cause changes to the skin at sites where insulin is
      administered. These changes may be felt as lumps under the skin. Insulin injected into these
      areas may not work as well leading to needing increasing doses of insulin to control blood
      glucose levels. Hypoglycemia can occur when insulin is injected into normal areas. Previous
      studies have found that these lipohypertrophic areas can be seen on ultrasound before they
      can be felt. The Investigators will be using the euglycemic clamp techique to evaluate
      insulin absorption to see whether tissue with lumps that cannot be felt but are seen on
      ultrasound affect how insulin is absorbed.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Double (Investigator, Outcomes Assessor)
masking description: During one euglycemic clamp study, insulin lispro will be injected subcutaneously into an area of subclinical lipohypertrophy of the abdomen identified by ultrasound, during the other insulin lispro will be injected to an area with no subclinical lipohypertrophy.
measure: Insulin Levels
time frame: 2 months
description: The euglycemic clamp technique will be used. Insulin levels will be analyzed by Eliza assay
arm group label: Subclinical Lipohypertrophy
arm group type: Other
description: Insulin lispro will be injected in the abdomen into an area of subclinical lipohypertrophy.
arm group label: No Subclinical Lipohypertrophy
arm group type: Other
description: Insulin lispro will be injected in the abdomen into an area where there is no subclinical lipohypertrophy.
intervention type: Drug
intervention name: Insulin lispro
description: Insulin lispro will be injected into the abdomen into an area of subclinical lipohypertrophy or an area with no subclinical lipohypertrophy
arm group label: No Subclinical Lipohypertrophy
arm group label: Subclinical Lipohypertrophy
criteria: 
gender: All
minimum age: 19 Years
maximum age: N/A
healthy volunteers: No
last name: Graydon Meneilly, MD
role: Principal Investigator
affiliation: University of British Columbia
facility: 
country: Canada
citation: Fujikura J, Fujimoto M, Yasue S, Noguchi M, Masuzaki H, Hosoda K, Tachibana T, Sugihara H, Nakao K. Insulin-induced lipohypertrophy: report of a case with histopathology. Endocr J. 2005 Oct;52(5):623-8. doi: 10.1507/endocrj.52.623.
PMID: 16284443
citation: Raile K, Noelle V, Landgraf R, Schwarz HP. Insulin antibodies are associated with lipoatrophy but also with lipohypertrophy in children and adolescents with type 1 diabetes. Exp Clin Endocrinol Diabetes. 2001;109(8):393-6. doi: 10.1055/s-2001-18991.
PMID: 11748486
citation: Schiazza L, Occella C, Bleidl D, Rampini E. Insulin lipohypertrophy. J Am Acad Dermatol. 1990 Jan;22(1):148-9. doi: 10.1016/s0190-9622(08)80037-0. No abstract available.
PMID: 2076114
citation: Vardar B, Kizilci S. Incidence of lipohypertrophy in diabetic patients and a study of influencing factors. Diabetes Res Clin Pract. 2007 Aug;77(2):231-6. doi: 10.1016/j.diabres.2006.12.023. Epub 2007 Feb 15.
PMID: 17303282
citation: Young RJ, Hannan WJ, Frier BM, Steel JM, Duncan LJ. Diabetic lipohypertrophy delays insulin absorption. Diabetes Care. 1984 Sep-Oct;7(5):479-80. doi: 10.2337/diacare.7.5.479.
PMID: 6389062
citation: Chowdhury TA, Escudier V. Poor glycaemic control caused by insulin induced lipohypertrophy. BMJ. 2003 Aug 16;327(7411):383-4. doi: 10.1136/bmj.327.7411.383. No abstract available.
PMID: 12919996
citation: Hauner H, Stockamp B, Haastert B. Prevalence of lipohypertrophy in insulin-treated diabetic patients and predisposing factors. Exp Clin Endocrinol Diabetes. 1996;104(2):106-10. doi: 10.1055/s-0029-1211431.
PMID: 8740933
citation: Blanco M, Hernandez MT, Strauss KW, Amaya M. Prevalence and risk factors of lipohypertrophy in insulin-injecting patients with diabetes. Diabetes Metab. 2013 Oct;39(5):445-53. doi: 10.1016/j.diabet.2013.05.006. Epub 2013 Jul 22.
PMID: 23886784
citation: Thow JC, Johnson AB, Marsden S, Taylor R, Home PD. Morphology of palpably abnormal injection sites and effects on absorption of isophane(NPH) insulin. Diabet Med. 1990 Nov;7(9):795-9. doi: 10.1111/j.1464-5491.1990.tb01494.x.
PMID: 2148131
citation: Overland J, Molyneaux L, Tewari S, Fatouros R, Melville P, Foote D, Wu T, Yue DK. Lipohypertrophy: does it matter in daily life? A study using a continuous glucose monitoring system. Diabetes Obes Metab. 2009 May;11(5):460-3. doi: 10.1111/j.1463-1326.2008.00972.x. Epub 2009 Feb 19.
PMID: 19236441
citation: Heinemann L, Weyer C, Rauhaus M, Heinrichs S, Heise T. Variability of the metabolic effect of soluble insulin and the rapid-acting insulin analog insulin aspart. Diabetes Care. 1998 Nov;21(11):1910-4. doi: 10.2337/diacare.21.11.1910.
PMID: 9802742
citation: Famulla S, Hovelmann U, Fischer A, Coester HV, Hermanski L, Kaltheuner M, Kaltheuner L, Heinemann L, Heise T, Hirsch L. Insulin Injection Into Lipohypertrophic Tissue: Blunted and More Variable Insulin Absorption and Action and Impaired Postprandial Glucose Control. Diabetes Care. 2016 Sep;39(9):1486-92. doi: 10.2337/dc16-0610. Epub 2016 Jul 13.
PMID: 27411698
responsible party type: Sponsor-Investigator
investigator affiliation: University of British Columbia
investigator full name: Graydon Meneilly
investigator title: Professor, UBC Department of Medicine
mesh term: Insulin Lispro
sharing ipd: No