<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/NCT01662921</url>
  </required_header>
  <id_info>
    <org_study_id>APIDRL06229</org_study_id>
    <nct_id>NCT01662921</nct_id>
  </id_info>
  <brief_title>Comparator Trial Using Insulin Glulisine vs. Insulin Lispro for Treatment of Gestational Diabetes</brief_title>
  <official_title>Non-inferiority Trial Comparing Insulin Glulisine to Insulin Lispro as Part of a Basal-bolus Insulin Regimen for the Treatment of Gestational Diabetes.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sansum Diabetes Research Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Sanofi</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Sansum Diabetes Research Institute</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      We hypothesize that insulin glulisine is non-inferior to currently proven rapid-acting&#xD;
      insulin lispro when used in a basal/bolus regimen to treat hyperglycemia in patients with&#xD;
      gestational diabetes mellitus.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      To date, only two rapid-acting insulin analogs have been shown to be safe and effective for&#xD;
      the treatment of diabetes during pregnancy: insulin aspart and insulin lispro.&#xD;
&#xD;
      The pharmacokinetics and pharmacodynamics of insulin glulisine are unique and insulin&#xD;
      glulisine may be the best rapid-acting analog for the treatment of post-prandial&#xD;
      hyperglycemia. We believe that insulin glulisine should be evaluated in women with&#xD;
      gestational diabetes for its potential efficacy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 2013</start_date>
  <completion_date type="Actual">August 31, 2015</completion_date>
  <primary_completion_date type="Actual">January 31, 2015</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>show that insulin glulisine is non-inferior to insulin lispro in a basal/bolus regimen to treat hyperglycemia in patient with gestational diabetes mellitus</measure>
    <time_frame>week 4 of insulin treatment</time_frame>
    <description>compare average 1-hour post prandial SMBG measurements between patients randomized to insulin glulisine or insulin lispro</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Serum blood glucose area under the curve (AUC) at one 4-hour in-clinic meal challenge</measure>
    <time_frame>week 2 of insulin treatment</time_frame>
    <description>patients will come to the study site under fasting conditions and eat a standardized meal in the morning post administration of insulin NPH and their randomized bolus insulin.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare A1C at enrollment and weekly until delivery</measure>
    <time_frame>up to 36 weeks</time_frame>
    <description>A1C is measured weekly at each pregnancy visit up to 26 visits. Subjects are enrolled at 20-32 weeks gestation and have weekly visits to obtain A1C through delivery, and again at the 6-week postpartum visit.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare incidence of hypoglycemic episodes &lt;60 mg/dL with symptoms</measure>
    <time_frame>up to 36 weeks</time_frame>
    <description>Hypoglycemic episodes since the last visit will be reported at each pregnancy visit, usually weekly, from enrollment at 10-30 weeks gestation through delivery and at the 6-week postpartum visit if continuing to take insulin.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Compare incidence of birth weight &gt;90th percentile</measure>
    <time_frame>delivery</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Compare incidence of primary cesarean section</measure>
    <time_frame>delivery</time_frame>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">17</enrollment>
  <condition>Diabetes During Pregnancy</condition>
  <arm_group>
    <arm_group_label>NPH and insulin lispro</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients diagnosed with diabetes during pregnancy will be randomized to long acting insulin NPH and short acting insulin lispro in a basal bolus regimen to treat post prandial hyperglycemia using a dosing schedule of 50% NPH calculated by the patients weight and gestational age and 50% lispro pending their last three SMPG average.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>NPH and insulin glulisine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients with a diagnosis of diabetes during pregnancy will be randomized to using long acting insulin NPH and short acting insulin glulisine as treatment for post prandial hyperglycemia with a 50% NPH dosing schedule based on the weight and gestational age and 50% glulisine schedule based on their last three SMBG result average.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>NPH</intervention_name>
    <description>Long acting insulin NPH dosing will be titrated weekly derived from the patients current weight and gestational age</description>
    <arm_group_label>NPH and insulin glulisine</arm_group_label>
    <arm_group_label>NPH and insulin lispro</arm_group_label>
    <other_name>Humulin N, Novolin N</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Insulin LISPRO</intervention_name>
    <description>Insulin lispro dosing will be titrated weekly based on the patient's average SMBG readings from each meal during the past three days</description>
    <arm_group_label>NPH and insulin lispro</arm_group_label>
    <other_name>Humalog</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Insulin glulisine</intervention_name>
    <description>Insulin glulisine will be titrated weekly based on the patient's average SMBG readings from each meal during the past three days</description>
    <arm_group_label>NPH and insulin glulisine</arm_group_label>
    <other_name>Apidra</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Informed Consent to participate in clinical trial&#xD;
&#xD;
          -  Pregnant and 20-30 weeks gestation&#xD;
&#xD;
          -  Diagnosed with gestational diabetes&#xD;
&#xD;
          -  Failed diet therapy (failed lifestyle modification will be defined as 10% or greater&#xD;
             SMBG values above pre-meal &lt;90mg/dL and post prandial &lt; 120mg/dL&#xD;
&#xD;
          -  Eat at least 2 meals per day&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant women &lt;18 years old&#xD;
&#xD;
          -  Blood pressure &gt; 140/80 mmHg&#xD;
&#xD;
          -  A1C equal to or greater than 6.5% at time of enrollment&#xD;
&#xD;
          -  Pre-pregnancy BMI &gt; 40Kg/m squared&#xD;
&#xD;
          -  Evidence of any fetal anomaly on any fetal ultrasound&#xD;
&#xD;
          -  Currently using hypoglycemic agent&#xD;
&#xD;
          -  Refusal to use insulin before meals&#xD;
&#xD;
          -  Inability to understand instructions or to consent to participate&#xD;
&#xD;
          -  Pregnant women with history of T1DM or T2DM&#xD;
&#xD;
          -  Clinical judgment by investigator that patient is inappropriate for clinical trial or&#xD;
             has a metabolic disorder that could interfere with results&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kristin Castorino, DO</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sansum Diabetes Research Institute</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Leonie Mattison, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Sansum Diabetes Research Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>William Sansum Diabetes Center</name>
      <address>
        <city>Santa Barbara</city>
        <state>California</state>
        <zip>93105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.sansum.org</url>
    <description>Web page for Sansum Diabetes Research Institute</description>
  </link>
  <reference>
    <citation>1. Centers for Disease Control and Prevention: National diabetes fact sheet: national estimates and general information on diabetes and prediabetes in the United States, 2011. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, 2011.</citation>
  </reference>
  <reference>
    <citation>Castorino K, Jovanovic L. Pregnancy and diabetes management: advances and controversies. Clin Chem. 2011 Feb;57(2):221-30. doi: 10.1373/clinchem.2010.155382. Epub 2010 Dec 9.</citation>
    <PMID>21148303</PMID>
  </reference>
  <reference>
    <citation>HAPO Study Cooperative Research Group; Metzger BE, Lowe LP, Dyer AR, Trimble ER, Chaovarindr U, Coustan DR, Hadden DR, McCance DR, Hod M, McIntyre HD, Oats JJ, Persson B, Rogers MS, Sacks DA. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med. 2008 May 8;358(19):1991-2002. doi: 10.1056/NEJMoa0707943.</citation>
    <PMID>18463375</PMID>
  </reference>
  <reference>
    <citation>Jovanovic L, Pettitt DJ. Treatment with insulin and its analogs in pregnancies complicated by diabetes. Diabetes Care. 2007 Jul;30 Suppl 2:S220-4. doi: 10.2337/dc07-s220. No abstract available. Erratum In: Diabetes Care. 2007 Dec;30(12):3154.</citation>
    <PMID>17596476</PMID>
  </reference>
  <reference>
    <citation>Arnolds S, Rave K, Hovelmann U, Fischer A, Sert-Langeron C, Heise T. Insulin glulisine has a faster onset of action compared with insulin aspart in healthy volunteers. Exp Clin Endocrinol Diabetes. 2010 Oct;118(9):662-4. doi: 10.1055/s-0030-1252067. Epub 2010 Apr 28.</citation>
    <PMID>20429049</PMID>
  </reference>
  <reference>
    <citation>Manderson JG, Patterson CC, Hadden DR, Traub AI, Ennis C, McCance DR. Preprandial versus postprandial blood glucose monitoring in type 1 diabetic pregnancy: a randomized controlled clinical trial. Am J Obstet Gynecol. 2003 Aug;189(2):507-12. doi: 10.1067/s0002-9378(03)00497-6.</citation>
    <PMID>14520226</PMID>
  </reference>
  <verification_date>April 2018</verification_date>
  <study_first_submitted>August 7, 2012</study_first_submitted>
  <study_first_submitted_qc>August 8, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 13, 2012</study_first_posted>
  <last_update_submitted>April 16, 2018</last_update_submitted>
  <last_update_submitted_qc>April 16, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">April 18, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>bolus treatment</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes, Gestational</mesh_term>
    <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>
    <mesh_term>Insulin, Globin Zinc</mesh_term>
    <mesh_term>Insulin Lispro</mesh_term>
    <mesh_term>Insulin glulisine</mesh_term>
    <mesh_term>Isophane Insulin, Human</mesh_term>
  </intervention_browse>
  <pending_results>
    <submitted>June 7, 2022</submitted>
    <returned>June 30, 2022</returned>
  </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/NCT01662921
org study id: APIDRL06229
nct id: NCT01662921
lead sponsor: 
collaborator: 
has dmc: No
We hypothesize that insulin glulisine is non-inferior to currently proven rapid-acting
      insulin lispro when used in a basal/bolus regimen to treat hyperglycemia in patients with
      gestational diabetes mellitus.
To date, only two rapid-acting insulin analogs have been shown to be safe and effective for
      the treatment of diabetes during pregnancy: insulin aspart and insulin lispro.

      The pharmacokinetics and pharmacodynamics of insulin glulisine are unique and insulin
      glulisine may be the best rapid-acting analog for the treatment of post-prandial
      hyperglycemia. We believe that insulin glulisine should be evaluated in women with
      gestational diabetes for its potential efficacy.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: show that insulin glulisine is non-inferior to insulin lispro in a basal/bolus regimen to treat hyperglycemia in patient with gestational diabetes mellitus
time frame: week 4 of insulin treatment
description: compare average 1-hour post prandial SMBG measurements between patients randomized to insulin glulisine or insulin lispro
measure: Serum blood glucose area under the curve (AUC) at one 4-hour in-clinic meal challenge
time frame: week 2 of insulin treatment
description: patients will come to the study site under fasting conditions and eat a standardized meal in the morning post administration of insulin NPH and their randomized bolus insulin.
measure: Compare A1C at enrollment and weekly until delivery
time frame: up to 36 weeks
description: A1C is measured weekly at each pregnancy visit up to 26 visits. Subjects are enrolled at 20-32 weeks gestation and have weekly visits to obtain A1C through delivery, and again at the 6-week postpartum visit.
measure: Compare incidence of hypoglycemic episodes <60 mg/dL with symptoms
time frame: up to 36 weeks
description: Hypoglycemic episodes since the last visit will be reported at each pregnancy visit, usually weekly, from enrollment at 10-30 weeks gestation through delivery and at the 6-week postpartum visit if continuing to take insulin.
measure: Compare incidence of birth weight >90th percentile
time frame: delivery
measure: Compare incidence of primary cesarean section
time frame: delivery
arm group label: NPH and insulin lispro
arm group type: Active Comparator
description: Patients diagnosed with diabetes during pregnancy will be randomized to long acting insulin NPH and short acting insulin lispro in a basal bolus regimen to treat post prandial hyperglycemia using a dosing schedule of 50% NPH calculated by the patients weight and gestational age and 50% lispro pending their last three SMPG average.
arm group label: NPH and insulin glulisine
arm group type: Active Comparator
description: Patients with a diagnosis of diabetes during pregnancy will be randomized to using long acting insulin NPH and short acting insulin glulisine as treatment for post prandial hyperglycemia with a 50% NPH dosing schedule based on the weight and gestational age and 50% glulisine schedule based on their last three SMBG result average.
intervention type: Drug
intervention name: NPH
description: Long acting insulin NPH dosing will be titrated weekly derived from the patients current weight and gestational age
arm group label: NPH and insulin glulisine
arm group label: NPH and insulin lispro
other name: Humulin N, Novolin N
intervention type: Drug
intervention name: Insulin LISPRO
description: Insulin lispro dosing will be titrated weekly based on the patient's average SMBG readings from each meal during the past three days
arm group label: NPH and insulin lispro
other name: Humalog
intervention type: Drug
intervention name: Insulin glulisine
description: Insulin glulisine will be titrated weekly based on the patient's average SMBG readings from each meal during the past three days
arm group label: NPH and insulin glulisine
other name: Apidra
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Kristin Castorino, DO
role: Principal Investigator
affiliation: Sansum Diabetes Research Institute
last name: Leonie Mattison, PhD
role: Study Director
affiliation: Sansum Diabetes Research Institute
facility: 
country: United States
url: http://www.sansum.org
description: Web page for Sansum Diabetes Research Institute
citation: 1. Centers for Disease Control and Prevention: National diabetes fact sheet: national estimates and general information on diabetes and prediabetes in the United States, 2011. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, 2011.
citation: Castorino K, Jovanovic L. Pregnancy and diabetes management: advances and controversies. Clin Chem. 2011 Feb;57(2):221-30. doi: 10.1373/clinchem.2010.155382. Epub 2010 Dec 9.
PMID: 21148303
citation: HAPO Study Cooperative Research Group; Metzger BE, Lowe LP, Dyer AR, Trimble ER, Chaovarindr U, Coustan DR, Hadden DR, McCance DR, Hod M, McIntyre HD, Oats JJ, Persson B, Rogers MS, Sacks DA. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med. 2008 May 8;358(19):1991-2002. doi: 10.1056/NEJMoa0707943.
PMID: 18463375
citation: Jovanovic L, Pettitt DJ. Treatment with insulin and its analogs in pregnancies complicated by diabetes. Diabetes Care. 2007 Jul;30 Suppl 2:S220-4. doi: 10.2337/dc07-s220. No abstract available. Erratum In: Diabetes Care. 2007 Dec;30(12):3154.
PMID: 17596476
citation: Arnolds S, Rave K, Hovelmann U, Fischer A, Sert-Langeron C, Heise T. Insulin glulisine has a faster onset of action compared with insulin aspart in healthy volunteers. Exp Clin Endocrinol Diabetes. 2010 Oct;118(9):662-4. doi: 10.1055/s-0030-1252067. Epub 2010 Apr 28.
PMID: 20429049
citation: Manderson JG, Patterson CC, Hadden DR, Traub AI, Ennis C, McCance DR. Preprandial versus postprandial blood glucose monitoring in type 1 diabetic pregnancy: a randomized controlled clinical trial. Am J Obstet Gynecol. 2003 Aug;189(2):507-12. doi: 10.1067/s0002-9378(03)00497-6.
PMID: 14520226
responsible party type: Sponsor
mesh term: Diabetes, Gestational
mesh term: Diabetes Mellitus
mesh term: Insulin
mesh term: Insulin, Globin Zinc
mesh term: Insulin Lispro
mesh term: Insulin glulisine
mesh term: Isophane Insulin, Human
submitted: June 7, 2022
returned: June 30, 2022