<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/NCT02229097</url>
  </required_header>
  <id_info>
    <org_study_id>13 7029 08</org_study_id>
    <secondary_id>2014-000969-47</secondary_id>
    <secondary_id>13-074</secondary_id>
    <nct_id>NCT02229097</nct_id>
  </id_info>
  <brief_title>Efficacy of Coordinated Insulin Boluses in Type 1 Diabetic Patients</brief_title>
  <acronym>COBOL</acronym>
  <official_title>Clinical Efficacy of Coordinated Boluses in Type 1 Diabetic Patients Treated With Insulin Pumps: a Multicentric, Randomised, Cross Over Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Toulouse</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Toulouse</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      A recent study suggests that, in Type 1 Diabetes (T1D) patients treated by insulin pumps, a&#xD;
      better coordination of meal boluses and post prandial basal rate could reduce the importance&#xD;
      of postprandial hyperglycaemias without increasing the risk of delayed hypoglycaemias.&#xD;
&#xD;
      The aim of the investigators study is to assess if these results are confirmed in a clinical&#xD;
      trial.&#xD;
&#xD;
      The aim of this study is to compare the efficacy of coordinated boluses versus normal boluses&#xD;
      on postprandial glycaemic control of T1D patients treated with continuous subcutaneous&#xD;
      insulin infusion.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 2014</start_date>
  <completion_date type="Actual">November 2016</completion_date>
  <primary_completion_date type="Actual">November 2016</primary_completion_date>
  <phase>Phase 4</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>postprandial glycaemia</measure>
    <time_frame>2 hours after eating during 4 weeks</time_frame>
    <description>measured by Self Monitoring of Blood Glucose</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>adverse events</measure>
    <time_frame>Throughout the study (4 weeks)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>severe hypoglycaemia frequency</measure>
    <time_frame>Throughout the study (4 weeks)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>insulin doses</measure>
    <time_frame>basal rate and boluses</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>mean glycaemia</measure>
    <time_frame>before eating and 2 hours after eating during 4 weeks</time_frame>
    <description>data from Self Monitoring of Blood Glucose</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>standard deviation of glycaemia</measure>
    <time_frame>before eating and 2 hours after eating during 4 weeks</time_frame>
    <description>data from Self Monitoring of Blood Glucose</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>frequency of glycaemia &lt; or = 60mg/dl</measure>
    <time_frame>before eating and 2 hours after eating during 4 weeks</time_frame>
    <description>data from Self Monitoring of Blood Glucose</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>frequency of glycaemia between 61-140mg/dl</measure>
    <time_frame>before eating and 2 hours after eating during 4 weeks</time_frame>
    <description>data from Self Monitoring of Blood Glucose</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>frequency of glycaemia &gt;140mg/dl</measure>
    <time_frame>before eating and 2 hours after eating during 4 weeks</time_frame>
    <description>data from Self Monitoring of Blood Glucose</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>mean glycemia</measure>
    <time_frame>Throughout the day during 4 weeks</time_frame>
    <description>data from Continue Glycemia Monitoring</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>standard deviation</measure>
    <time_frame>Throughout the day during 4 weeks</time_frame>
    <description>data from Continue Glycemia Monitoring</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>time spent within glucose range &lt; or = 60mg/dl</measure>
    <time_frame>Throughout the day during 4 weeks</time_frame>
    <description>data from Continue Glycemia Monitoring</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>time spent within glucose range between 61-140mg/dl</measure>
    <time_frame>Throughout the day during 4 weeks</time_frame>
    <description>data from Continue Glycemia Monitoring</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>time spent within glucose range mg/dl</measure>
    <time_frame>Throughout the day during 4 weeks</time_frame>
    <description>data from Continue Glycemia Monitoring</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>fructosamine</measure>
    <time_frame>day 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>fructosamine</measure>
    <time_frame>day 1 + 2 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>fructosamine</measure>
    <time_frame>day 1 + 4 weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">17</enrollment>
  <condition>Type 1 Diabetes</condition>
  <arm_group>
    <arm_group_label>Normal then Coordinated</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>normal bolus during 2 weeks then coordinated bolus during 2 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Coordinated then Normal</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>coordinated bolus during 2 weeks then normal bolus during 2 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Normal bolus</intervention_name>
    <description>During the &quot;normal bolus&quot; period, the bolus will be adjusted to the carbohydrate content of each meal and injected immediately. The basal rate will remain at a normal level during the 3 hours postprandial period</description>
    <arm_group_label>Coordinated then Normal</arm_group_label>
    <arm_group_label>Normal then Coordinated</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Coordinated bolus</intervention_name>
    <description>The basal rate will be reduced at a rate of 0.1 U/h during the 3 h postprandial period. The insulin subtracted of the basal rate will be added to the normal bolus calculated for the meal and injected immediately.</description>
    <arm_group_label>Coordinated then Normal</arm_group_label>
    <arm_group_label>Normal then Coordinated</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Type 1 diabetes mellitus&#xD;
&#xD;
          -  with confirmed Negative C-peptide or diabetes duration&gt;5 years&#xD;
&#xD;
          -  Treated by external insulin pump and rapid insulin analog for more than 3 months&#xD;
&#xD;
          -  using a Medtronic Paradigm Real-Time or Veo™ model&#xD;
&#xD;
          -  Educated to and practicing functional insulin treatment and carbohydrate counting for&#xD;
             more than 3 months&#xD;
&#xD;
          -  Able to use the &quot;basal temp&quot; and &quot;glycaemia reminder&quot; functions of their pump&#xD;
&#xD;
          -  Basal infusion rate ≥ 0,5 Unit/h&#xD;
&#xD;
          -  Self-monitoring of blood glucose frequency &gt; 4/days&#xD;
&#xD;
          -  Aware of hypoglycaemia&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  known impaired renal function (creatinin clearance &lt;60ml/min)&#xD;
&#xD;
          -  Gastroparesis&#xD;
&#xD;
          -  Serious or instable disease likely to induce a glycaemic control deterioration -&#xD;
             treatment with corticosteroids&#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>Vincent Melki, Doctor</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital, Toulouse</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospital Toulouse Rangueil</name>
      <address>
        <city>Toulouse</city>
        <state>Haute Garonne</state>
        <zip>31059</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint-André Hospital</name>
      <address>
        <city>Bordeaux</city>
        <zip>33000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lapeyronie Hospital</name>
      <address>
        <city>Montpellier</city>
        <zip>34295</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <reference>
    <citation>Bondia J, Dassau E, Zisser H, Calm R, Vehi J, Jovanovic L, Doyle FJ 3rd. Coordinated basal-bolus infusion for tighter postprandial glucose control in insulin pump therapy. J Diabetes Sci Technol. 2009 Jan;3(1):89-97. doi: 10.1177/193229680900300110.</citation>
    <PMID>20046653</PMID>
  </reference>
  <reference>
    <citation>A. Farret, B. Catargi, J.P. Riveline, V. Melki, P. Schaepelynck, A. Sola, B. Guerci, H. Bertet, T. Mura, H. Chevassus, E. Renard : Étude randomisée contrôlée en cross-over comparant les effets sur le contrôle glycémique des bolus immédiats et combinés chez des patients diabétiques de type 1 traités par pompe à insuline portable. Diabetes &amp; Metabolism, Volume 38, Supplement 2, March 2012, Page A6</citation>
  </reference>
  <reference>
    <citation>Druet C, Roudier C, Romon I, Assogba F, Bourdel-Marchasson I, et al. Échantillon national témoin représentatif des personnes diabétiques, Entred 2007-2010.</citation>
  </reference>
  <reference>
    <citation>Diabetes Control and Complications Trial Research Group; Nathan DM, Genuth S, Lachin J, Cleary P, Crofford O, Davis M, Rand L, Siebert C. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993 Sep 30;329(14):977-86. doi: 10.1056/NEJM199309303291401.</citation>
    <PMID>8366922</PMID>
  </reference>
  <reference>
    <citation>Nathan DM, Cleary PA, Backlund JY, Genuth SM, Lachin JM, Orchard TJ, Raskin P, Zinman B; Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study Research Group. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med. 2005 Dec 22;353(25):2643-53. doi: 10.1056/NEJMoa052187.</citation>
    <PMID>16371630</PMID>
  </reference>
  <reference>
    <citation>Etude Jubilé. SFD 2013</citation>
  </reference>
  <reference>
    <citation>Pickup J, Mattock M, Kerry S. Glycaemic control with continuous subcutaneous insulin infusion compared with intensive insulin injections in patients with type 1 diabetes: meta-analysis of randomised controlled trials. BMJ. 2002 Mar 23;324(7339):705. doi: 10.1136/bmj.324.7339.705.</citation>
    <PMID>11909787</PMID>
  </reference>
  <reference>
    <citation>Mudaliar SR, Lindberg FA, Joyce M, Beerdsen P, Strange P, Lin A, Henry RR. Insulin aspart (B28 asp-insulin): a fast-acting analog of human insulin: absorption kinetics and action profile compared with regular human insulin in healthy nondiabetic subjects. Diabetes Care. 1999 Sep;22(9):1501-6. doi: 10.2337/diacare.22.9.1501.</citation>
    <PMID>10480516</PMID>
  </reference>
  <reference>
    <citation>Directive pour la gestion de la glycémie post prandiale, IDF 2007 http://www.idf.org/webdata/docs/French_GMPG Final 110108.pdf</citation>
  </reference>
  <reference>
    <citation>Melki.v, Cazals.l : Impact de la coordination des bolus et du débit de base sur le contrôle des glycémies postprandiales chez des diabétiques de type 1 traités par pompe externe (étude pilote). Poster accepté SFD 2014</citation>
  </reference>
  <verification_date>July 2016</verification_date>
  <study_first_submitted>August 26, 2014</study_first_submitted>
  <study_first_submitted_qc>August 28, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 29, 2014</study_first_posted>
  <last_update_submitted>February 21, 2017</last_update_submitted>
  <last_update_submitted_qc>February 21, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">February 23, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>type 1 diabetes</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus, Type 1</mesh_term>
  </condition_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/NCT02229097
org study id: 13 7029 08
secondary id: 2014-000969-47
secondary id: 13-074
nct id: NCT02229097
lead sponsor: 
has dmc: No
A recent study suggests that, in Type 1 Diabetes (T1D) patients treated by insulin pumps, a
      better coordination of meal boluses and post prandial basal rate could reduce the importance
      of postprandial hyperglycaemias without increasing the risk of delayed hypoglycaemias.

      The aim of the investigators study is to assess if these results are confirmed in a clinical
      trial.

      The aim of this study is to compare the efficacy of coordinated boluses versus normal boluses
      on postprandial glycaemic control of T1D patients treated with continuous subcutaneous
      insulin infusion.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: postprandial glycaemia
time frame: 2 hours after eating during 4 weeks
description: measured by Self Monitoring of Blood Glucose
measure: adverse events
time frame: Throughout the study (4 weeks)
measure: severe hypoglycaemia frequency
time frame: Throughout the study (4 weeks)
measure: insulin doses
time frame: basal rate and boluses
measure: mean glycaemia
time frame: before eating and 2 hours after eating during 4 weeks
description: data from Self Monitoring of Blood Glucose
measure: standard deviation of glycaemia
time frame: before eating and 2 hours after eating during 4 weeks
description: data from Self Monitoring of Blood Glucose
measure: frequency of glycaemia < or = 60mg/dl
time frame: before eating and 2 hours after eating during 4 weeks
description: data from Self Monitoring of Blood Glucose
measure: frequency of glycaemia between 61-140mg/dl
time frame: before eating and 2 hours after eating during 4 weeks
description: data from Self Monitoring of Blood Glucose
measure: frequency of glycaemia >140mg/dl
time frame: before eating and 2 hours after eating during 4 weeks
description: data from Self Monitoring of Blood Glucose
measure: mean glycemia
time frame: Throughout the day during 4 weeks
description: data from Continue Glycemia Monitoring
measure: standard deviation
time frame: Throughout the day during 4 weeks
description: data from Continue Glycemia Monitoring
measure: time spent within glucose range < or = 60mg/dl
time frame: Throughout the day during 4 weeks
description: data from Continue Glycemia Monitoring
measure: time spent within glucose range between 61-140mg/dl
time frame: Throughout the day during 4 weeks
description: data from Continue Glycemia Monitoring
measure: time spent within glucose range mg/dl
time frame: Throughout the day during 4 weeks
description: data from Continue Glycemia Monitoring
measure: fructosamine
time frame: day 1
measure: fructosamine
time frame: day 1 + 2 weeks
measure: fructosamine
time frame: day 1 + 4 weeks
arm group label: Normal then Coordinated
arm group type: Experimental
description: normal bolus during 2 weeks then coordinated bolus during 2 weeks
arm group label: Coordinated then Normal
arm group type: Experimental
description: coordinated bolus during 2 weeks then normal bolus during 2 weeks
intervention type: Drug
intervention name: Normal bolus
description: During the "normal bolus" period, the bolus will be adjusted to the carbohydrate content of each meal and injected immediately. The basal rate will remain at a normal level during the 3 hours postprandial period
arm group label: Coordinated then Normal
arm group label: Normal then Coordinated
intervention type: Drug
intervention name: Coordinated bolus
description: The basal rate will be reduced at a rate of 0.1 U/h during the 3 h postprandial period. The insulin subtracted of the basal rate will be added to the normal bolus calculated for the meal and injected immediately.
arm group label: Coordinated then Normal
arm group label: Normal then Coordinated
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Vincent Melki, Doctor
role: Principal Investigator
affiliation: University Hospital, Toulouse
facility: 
facility: 
facility: 
country: France
citation: Bondia J, Dassau E, Zisser H, Calm R, Vehi J, Jovanovic L, Doyle FJ 3rd. Coordinated basal-bolus infusion for tighter postprandial glucose control in insulin pump therapy. J Diabetes Sci Technol. 2009 Jan;3(1):89-97. doi: 10.1177/193229680900300110.
PMID: 20046653
citation: A. Farret, B. Catargi, J.P. Riveline, V. Melki, P. Schaepelynck, A. Sola, B. Guerci, H. Bertet, T. Mura, H. Chevassus, E. Renard : Étude randomisée contrôlée en cross-over comparant les effets sur le contrôle glycémique des bolus immédiats et combinés chez des patients diabétiques de type 1 traités par pompe à insuline portable. Diabetes & Metabolism, Volume 38, Supplement 2, March 2012, Page A6
citation: Druet C, Roudier C, Romon I, Assogba F, Bourdel-Marchasson I, et al. Échantillon national témoin représentatif des personnes diabétiques, Entred 2007-2010.
citation: Diabetes Control and Complications Trial Research Group; Nathan DM, Genuth S, Lachin J, Cleary P, Crofford O, Davis M, Rand L, Siebert C. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993 Sep 30;329(14):977-86. doi: 10.1056/NEJM199309303291401.
PMID: 8366922
citation: Nathan DM, Cleary PA, Backlund JY, Genuth SM, Lachin JM, Orchard TJ, Raskin P, Zinman B; Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study Research Group. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med. 2005 Dec 22;353(25):2643-53. doi: 10.1056/NEJMoa052187.
PMID: 16371630
citation: Etude Jubilé. SFD 2013
citation: Pickup J, Mattock M, Kerry S. Glycaemic control with continuous subcutaneous insulin infusion compared with intensive insulin injections in patients with type 1 diabetes: meta-analysis of randomised controlled trials. BMJ. 2002 Mar 23;324(7339):705. doi: 10.1136/bmj.324.7339.705.
PMID: 11909787
citation: Mudaliar SR, Lindberg FA, Joyce M, Beerdsen P, Strange P, Lin A, Henry RR. Insulin aspart (B28 asp-insulin): a fast-acting analog of human insulin: absorption kinetics and action profile compared with regular human insulin in healthy nondiabetic subjects. Diabetes Care. 1999 Sep;22(9):1501-6. doi: 10.2337/diacare.22.9.1501.
PMID: 10480516
citation: Directive pour la gestion de la glycémie post prandiale, IDF 2007 http://www.idf.org/webdata/docs/French_GMPG Final 110108.pdf
citation: Melki.v, Cazals.l : Impact de la coordination des bolus et du débit de base sur le contrôle des glycémies postprandiales chez des diabétiques de type 1 traités par pompe externe (étude pilote). Poster accepté SFD 2014
responsible party type: Sponsor
mesh term: Diabetes Mellitus, Type 1
sharing ipd: No