<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/NCT01666028</url>
  </required_header>
  <id_info>
    <org_study_id>AP@home02</org_study_id>
    <nct_id>NCT01666028</nct_id>
  </id_info>
  <brief_title>Short Term Closed-loop Glucose Control in Adults With Type 1 Diabetes</brief_title>
  <acronym>AP@home02</acronym>
  <official_title>An Open-label, Three-centre, Randomised, Two-period Crossover Study to Assess the Safety, Efficacy and Utility of Automated Closed-loop Glucose Control in Comparison With Continuous Subcutaneous Insulin Infusion Combined With Continuous Glucose Monitoring in Adults With Type 1 Diabetes - A Combined Clinical Research Facility and Home Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Cambridge</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Cambridge University Hospitals NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Profil Institut für Stoffwechselforschung GmbH</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Medical University of Graz</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Cambridge</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The main objective of this study is to determine the feasibility, efficacy and safety of&#xD;
      automated closed-loop glucose control in the home setting over a short term period. The data&#xD;
      and experienced gained from this study will be utilised in planning future home studies.&#xD;
&#xD;
      This is an open-label, three centre, randomised, crossover design, involving two, 8 day&#xD;
      (first day in the clinical research facility and seven days at home) study periods during&#xD;
      which glucose levels will be controlled either by an automated closed-loop system or by&#xD;
      subjects usual insulin pump therapy in random order. A total of up to 24 adults (aiming for&#xD;
      18 completed subjects) aged 18 years and older with T1D on insulin pump therapy will be&#xD;
      recruited through diabetes clinics and other established methods in participating centres.&#xD;
&#xD;
      Subjects will receive appropriate training in the safe use of closed-loop insulin delivery&#xD;
      system. During the 24 hour in-patient stay subjects will be encouraged to mimic their usual&#xD;
      day and will be allowed to walk inside hospital premises. Subjects will be advised to&#xD;
      discontinue automated closed-loop insulin delivery and follow their usual insulin pump&#xD;
      therapy for periods of strenuous exercise during the 7 day home study phase.&#xD;
&#xD;
      The primary outcome is time spent in target range between 3.9 and 10.0 mmol/L as recorded by&#xD;
      CGM (adjusted for potential over-estimation) during home stay. Secondary outcomes are the&#xD;
      time spent with glucose levels above and below target, as recorded by CGM, and other&#xD;
      CGM-based metrics, and for the stay at the clinical research facility, time spent in the&#xD;
      target range, above and below the target range as measured by plasma glucose.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>November 2012</start_date>
  <completion_date type="Actual">November 2013</completion_date>
  <primary_completion_date type="Actual">November 2013</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>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time spent in the target glucose range from 3.9 to 10.0 mmol/l based on subcutaneous glucose monitoring (CGM) adjusted for sensor error.</measure>
    <time_frame>7 day home study period</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time spent above and below the target glucose (3.9 to 10.0 mmol/l) based on continuous subcutaneous glucose monitoring (CGM)</measure>
    <time_frame>7 day home study period</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Average and standard deviation glucose levels based on continuous subcutaneous glucose monitoring</measure>
    <time_frame>7 day home study period</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The time with glucose levels &lt; 3.5 mmol/l and &lt;2.8 mmol/l based on continuous subcutaneous glucose monitoring</measure>
    <time_frame>7 Day home study period</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The time with glucose levels in the significant hyperglycaemia, as based on continuous subcutaneous glucose monitoring (glucose levels &gt; 16.7 mmol/l)</measure>
    <time_frame>7 day home study period</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Low Blood Glucose Index (LBGI) based on continuous subcutaneous glucose monitoring</measure>
    <time_frame>7 day Home study period</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>During 24 hour in-patient stay - Same glucose metrics as during 7 day home stay but calculated based on continuous subcutaneous glucose monitoring (CGM) and plasma glucose measurements.</measure>
    <time_frame>24 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of episodes of hypoglycaemia, severe hypoglycaemia as well as nature and severity of any other adverse events.</measure>
    <time_frame>8 days</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Duration of use of the closed-loop system at home.</measure>
    <time_frame>7 days</time_frame>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Type 1 Diabetes</condition>
  <arm_group>
    <arm_group_label>Closed Loop Glucose control</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subject's glucose level is controlled by the automated closed loop glucose control system</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CSII with real-time CGM</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subject glucose level controlled by usual insulin pump therapy in conjunction with real time continuous glucose monitoring (CGM)</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>FlorenceD or similar closed loop glucose control system</intervention_name>
    <description>Subject's glucose level will be controlled by the FlorenceD or similar automated closed loop glucose control system. The system comprises of FreeStyle Navigator® Continuous Glucose Monitoring (CGM) System (Abbott Diabetes Care, Alameda, CA, USA), Dana R Diabecare subcutaneous insulin infusion pump (Sooil Corp. Seoul, South Korea)or similar insulin pump, and MPC-based glucose control algorithm running on a portable computer.</description>
    <arm_group_label>Closed Loop Glucose control</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>CSII with real-time CGM</intervention_name>
    <description>Subject glucose level controlled by usual insulin pump therapy in conjunction with real time continuous glucose monitoring (CGM)</description>
    <arm_group_label>CSII with real-time CGM</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. The subject has type 1 diabetes as defined by WHO&#xD;
&#xD;
          2. The subject is 18 years of age or older&#xD;
&#xD;
          3. The subject will have been on an insulin pump for at least 3 months currently using&#xD;
             insulin Aspart, with good knowledge of insulin self-adjustment including carbohydrate&#xD;
             counting&#xD;
&#xD;
          4. HbA1c ≤ 10 % based on analysis from local laboratory&#xD;
&#xD;
          5. The subject is willing to perform regular finger-prick blood glucose monitoring, with&#xD;
             at least 6 measurements per day during the 7 day home phase of the study&#xD;
&#xD;
          6. The subject is willing to wear closed-loop system at home and at work place&#xD;
&#xD;
          7. The subject is willing to follow study specific instructions&#xD;
&#xD;
          8. The subject is literate in English&#xD;
&#xD;
          9. Female subjects of child bearing age should be on effective contraception and must&#xD;
             have a negative urine-HCG pregnancy test at screening. In addition in Germany, women&#xD;
             of childbearing potential must use a highly effective method of birth control, which&#xD;
             is defined as those which result in a low failure rate (i.e. less than 1% per year)&#xD;
             and must use two independent methods of contraception, e.g. diaphragm and&#xD;
             spermicide-coated condom.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Non-type 1 diabetes mellitus&#xD;
&#xD;
          2. Any other physical or psychological disease or condition likely to interfere with the&#xD;
             normal conduct of the study and interpretation of the study results&#xD;
&#xD;
          3. Current treatment with drugs known to have significant interference with glucose&#xD;
             metabolism, such as systemic corticosteroids, as judged by the investigator&#xD;
&#xD;
          4. Known or suspected allergy against insulin&#xD;
&#xD;
          5. Subjects with clinically significant nephropathy, neuropathy or proliferative&#xD;
             retinopathy as judged by the investigator&#xD;
&#xD;
          6. Significantly reduced hypoglycaemia awareness as judged by the investigator&#xD;
&#xD;
          7. Total daily insulin dose more than 2 IU/kg/day&#xD;
&#xD;
          8. Subject is pregnant or breast feeding or planning pregnancy in near future (within&#xD;
             next 3 months)&#xD;
&#xD;
          9. Severe visual impairment&#xD;
&#xD;
         10. Severe hearing impairment&#xD;
&#xD;
         11. Subjects using implanted internal pacemaker&#xD;
&#xD;
         12. Lack of reliable telephone facility for contact&#xD;
&#xD;
        Additional exclusion criteria specific for Austria and Germany&#xD;
&#xD;
          1. Positive results on urine drug screen (amphetamines/metamphetamines, barbiturates,&#xD;
             benzodiazepines, cannabinoids, cocaine, opiates).&#xD;
&#xD;
          2. Positive alcohol breath test.&#xD;
&#xD;
        Additional exclusion criteria specific for Germany only&#xD;
&#xD;
        Positive reaction to any of the following tests: hepatitis B surface (HBs) antigen,&#xD;
        anti-hepatitis C virus (anti-HCV) antibodies, anti-human immunodeficiency virus (HIV) 1&#xD;
        antibodies, anti-HIV2 antibodies&#xD;
&#xD;
        -&#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>Mark Evans, FRCP (UK) MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Cambridge</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Sabine Arnolds, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Profil Institut für Stoffwechselforschung GmbH</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Thomas Pieber, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medical University of Graz</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Roman Hovorka, PhD</last_name>
    <role>Study Director</role>
    <affiliation>University of Cambridge</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Medical University of Graz</name>
      <address>
        <city>Graz</city>
        <zip>A- 8036</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Profil Institut für Stoffwechselforschung GmbH</name>
      <address>
        <city>Neuss</city>
        <zip>D-41460</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cambridge University Hospitals NHS Foundation Trust</name>
      <address>
        <city>Cambridge</city>
        <state>Cambridgeshire</state>
        <zip>CB2 0QQ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Austria</country>
    <country>Germany</country>
    <country>United Kingdom</country>
  </location_countries>
  <reference>
    <citation>Hovorka R, Allen JM, Elleri D, Chassin LJ, Harris J, Xing D, Kollman C, Hovorka T, Larsen AM, Nodale M, De Palma A, Wilinska ME, Acerini CL, Dunger DB. Manual closed-loop insulin delivery in children and adolescents with type 1 diabetes: a phase 2 randomised crossover trial. Lancet. 2010 Feb 27;375(9716):743-51. doi: 10.1016/S0140-6736(09)61998-X. Epub 2010 Feb 4.</citation>
    <PMID>20138357</PMID>
  </reference>
  <reference>
    <citation>Hovorka R, Kumareswaran K, Harris J, Allen JM, Elleri D, Xing D, Kollman C, Nodale M, Murphy HR, Dunger DB, Amiel SA, Heller SR, Wilinska ME, Evans ML. Overnight closed loop insulin delivery (artificial pancreas) in adults with type 1 diabetes: crossover randomised controlled studies. BMJ. 2011 Apr 13;342:d1855. doi: 10.1136/bmj.d1855.</citation>
    <PMID>21493665</PMID>
  </reference>
  <verification_date>December 2014</verification_date>
  <study_first_submitted>August 9, 2012</study_first_submitted>
  <study_first_submitted_qc>August 13, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 16, 2012</study_first_posted>
  <last_update_submitted>December 1, 2014</last_update_submitted>
  <last_update_submitted_qc>December 1, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 2, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Cambridge</investigator_affiliation>
    <investigator_full_name>Dr Roman Hovorka</investigator_full_name>
    <investigator_title>Principal Research Associate</investigator_title>
  </responsible_party>
  <keyword>Type 1 Diabetes</keyword>
  <keyword>Closed Loop glucose control</keyword>
  <keyword>Artificial Pancreas</keyword>
  <keyword>CSII</keyword>
  <keyword>CGM</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 1</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01666028
org study id: AP@home02
nct id: NCT01666028
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
The main objective of this study is to determine the feasibility, efficacy and safety of
      automated closed-loop glucose control in the home setting over a short term period. The data
      and experienced gained from this study will be utilised in planning future home studies.

      This is an open-label, three centre, randomised, crossover design, involving two, 8 day
      (first day in the clinical research facility and seven days at home) study periods during
      which glucose levels will be controlled either by an automated closed-loop system or by
      subjects usual insulin pump therapy in random order. A total of up to 24 adults (aiming for
      18 completed subjects) aged 18 years and older with T1D on insulin pump therapy will be
      recruited through diabetes clinics and other established methods in participating centres.

      Subjects will receive appropriate training in the safe use of closed-loop insulin delivery
      system. During the 24 hour in-patient stay subjects will be encouraged to mimic their usual
      day and will be allowed to walk inside hospital premises. Subjects will be advised to
      discontinue automated closed-loop insulin delivery and follow their usual insulin pump
      therapy for periods of strenuous exercise during the 7 day home study phase.

      The primary outcome is time spent in target range between 3.9 and 10.0 mmol/L as recorded by
      CGM (adjusted for potential over-estimation) during home stay. Secondary outcomes are the
      time spent with glucose levels above and below target, as recorded by CGM, and other
      CGM-based metrics, and for the stay at the clinical research facility, time spent in the
      target range, above and below the target range as measured by plasma glucose.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Time spent in the target glucose range from 3.9 to 10.0 mmol/l based on subcutaneous glucose monitoring (CGM) adjusted for sensor error.
time frame: 7 day home study period
measure: Time spent above and below the target glucose (3.9 to 10.0 mmol/l) based on continuous subcutaneous glucose monitoring (CGM)
time frame: 7 day home study period
measure: Average and standard deviation glucose levels based on continuous subcutaneous glucose monitoring
time frame: 7 day home study period
measure: The time with glucose levels < 3.5 mmol/l and <2.8 mmol/l based on continuous subcutaneous glucose monitoring
time frame: 7 Day home study period
measure: The time with glucose levels in the significant hyperglycaemia, as based on continuous subcutaneous glucose monitoring (glucose levels > 16.7 mmol/l)
time frame: 7 day home study period
measure: Low Blood Glucose Index (LBGI) based on continuous subcutaneous glucose monitoring
time frame: 7 day Home study period
measure: During 24 hour in-patient stay - Same glucose metrics as during 7 day home stay but calculated based on continuous subcutaneous glucose monitoring (CGM) and plasma glucose measurements.
time frame: 24 hours
measure: Number of episodes of hypoglycaemia, severe hypoglycaemia as well as nature and severity of any other adverse events.
time frame: 8 days
measure: Duration of use of the closed-loop system at home.
time frame: 7 days
arm group label: Closed Loop Glucose control
arm group type: Experimental
description: Subject's glucose level is controlled by the automated closed loop glucose control system
arm group label: CSII with real-time CGM
arm group type: Active Comparator
description: Subject glucose level controlled by usual insulin pump therapy in conjunction with real time continuous glucose monitoring (CGM)
intervention type: Device
intervention name: FlorenceD or similar closed loop glucose control system
description: Subject's glucose level will be controlled by the FlorenceD or similar automated closed loop glucose control system. The system comprises of FreeStyle Navigator® Continuous Glucose Monitoring (CGM) System (Abbott Diabetes Care, Alameda, CA, USA), Dana R Diabecare subcutaneous insulin infusion pump (Sooil Corp. Seoul, South Korea)or similar insulin pump, and MPC-based glucose control algorithm running on a portable computer.
arm group label: Closed Loop Glucose control
intervention type: Device
intervention name: CSII with real-time CGM
description: Subject glucose level controlled by usual insulin pump therapy in conjunction with real time continuous glucose monitoring (CGM)
arm group label: CSII with real-time CGM
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Mark Evans, FRCP (UK) MD
role: Principal Investigator
affiliation: University of Cambridge
last name: Sabine Arnolds, MD
role: Principal Investigator
affiliation: Profil Institut für Stoffwechselforschung GmbH
last name: Thomas Pieber, MD
role: Principal Investigator
affiliation: Medical University of Graz
last name: Roman Hovorka, PhD
role: Study Director
affiliation: University of Cambridge
facility: 
facility: 
facility: 
country: Austria
country: Germany
country: United Kingdom
citation: Hovorka R, Allen JM, Elleri D, Chassin LJ, Harris J, Xing D, Kollman C, Hovorka T, Larsen AM, Nodale M, De Palma A, Wilinska ME, Acerini CL, Dunger DB. Manual closed-loop insulin delivery in children and adolescents with type 1 diabetes: a phase 2 randomised crossover trial. Lancet. 2010 Feb 27;375(9716):743-51. doi: 10.1016/S0140-6736(09)61998-X. Epub 2010 Feb 4.
PMID: 20138357
citation: Hovorka R, Kumareswaran K, Harris J, Allen JM, Elleri D, Xing D, Kollman C, Nodale M, Murphy HR, Dunger DB, Amiel SA, Heller SR, Wilinska ME, Evans ML. Overnight closed loop insulin delivery (artificial pancreas) in adults with type 1 diabetes: crossover randomised controlled studies. BMJ. 2011 Apr 13;342:d1855. doi: 10.1136/bmj.d1855.
PMID: 21493665
responsible party type: Principal Investigator
investigator affiliation: University of Cambridge
investigator full name: Dr Roman Hovorka
investigator title: Principal Research Associate
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 1