<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/NCT01712594</url>
  </required_header>
  <id_info>
    <org_study_id>CEP223</org_study_id>
    <nct_id>NCT01712594</nct_id>
  </id_info>
  <brief_title>Safety and Effectiveness Study of a Closed Loop System Maintaining Patients' Glucose Levels During an Overnight Period</brief_title>
  <official_title>Feasibility and Safety of a Closed Loop Insulin Delivery System (Aka AAGC) With an Artificially Induced Calibration Error During the Overnight Period</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medtronic Diabetes</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Medtronic Diabetes</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_unapproved_device>Yes</is_unapproved_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Currently, patients diagnosed with type 1 diabetes rely on either finger stick or sensor&#xD;
      glucose readings when making their insulin dosage decisions. Designing a computerized system&#xD;
      that mimics the way insulin is produced naturally in a person who does not have type 1&#xD;
      diabetes holds many challenges; all of which cannot be addressed in just one study. The&#xD;
      purpose of the Medtronic Overnight Closed Loop study is to assess the performance of a system&#xD;
      designed to automatically infuse the correct insulin dose during the hours that the patient&#xD;
      is sleeping.&#xD;
&#xD;
      The system consists of an insulin pump that provides insulin to the patient through an&#xD;
      infusion set. A sensor inserted just under the patient's skin measures glucose levels and a&#xD;
      transmitter sends this information to the pump. To enable the sensor to register the glucose&#xD;
      information correctly, it must be set (calibrated) by a finger stick blood glucose 3-4 times&#xD;
      a day. In the commercially released system, the physician would recommend the continuous&#xD;
      background (basal) insulin rates and the patient would be required to make decisions&#xD;
      regarding extra insulin (bolus) for meals or as a response to high glucose levels.&#xD;
&#xD;
      In the Closed Loop System, a mobile control system is added to these devices. This consists&#xD;
      of an Android phone, a closed loop algorithm and a translator. This system is designed to&#xD;
      translate the sensor information and direct the pump to provide the required dosage of&#xD;
      insulin automatically without requiring input from the patient.&#xD;
&#xD;
      Reliable calibration has proved challenging, and so it is important that the system function&#xD;
      safely, even when calibration is inaccurate. In this study, a calibration error will be&#xD;
      introduced under very controlled circumstances. This testing will identify if the system can&#xD;
      maintain acceptable overnight glucose levels, regardless of whether or not calibration is&#xD;
      ideal.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>May 2013</start_date>
  <completion_date type="Actual">December 2014</completion_date>
  <primary_completion_date type="Actual">December 2013</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Amount of time spent in the target range defined as 3.8-8.8 mmol/l (70 to 160 mg/dL) YSI glucose during in-clinic overnight visits</measure>
    <time_frame>Two in-patient nights</time_frame>
    <description>Subjects will arrive at the research facility between 17:00 and 18:00. Plasma glucose will be measured and they will have their evening meal of no more than 80 g of carbohydrate. They will bolus for this meal using their usual Bolus Wizard (Medtronic) settings. After the meal, an IV catheter will be inserted for the collection of venous blood samples. The Mobile Control System will be connected and closed-loop control will be started approximately 4 hours after dinner. The subject will remain under closed-loop control overnight (approximately 11 p.m.-6 a.m.). During one of the Closed Loop nights the system will be challenged by a calibration error of 30%. At approximately 7 am (before breakfast), the Mobile Control System will be turned off and the patient will be provided with a breakfast (approximately 40-70 gm of carbohydrate) and will take a bolus according to the Bolus Wizard. The patient will return to their usual pump treatment with the MiniMed Paradigm Veo System.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Glucose Area under the curve (AUC) below 3.8 mmol/l (70 mg/dL ) YSI glucose obtained during in-clinic overnight visits</measure>
    <time_frame>Two overnight closed loop sessions</time_frame>
    <description>Blood glucose samples will be obtained from the line approximately every 30 minutes, or every 5-15 minutes at treating physician's discretion, if either the sensor or a previous glucose reading is &lt; 81mg/dL or &gt; 360mg/dL (&lt; 3.5 mmol/l or &gt; 20 mmol/l). Plasma samples will be analyzed using a YSI 2300 Glucose and Lactate Analyzer between 18:00 and 6:00.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Glucose AUC above 8.8mmol/l (160 mg/dL) YSI glucose obtained during in-clinic overnight visits</measure>
    <time_frame>Two overnight closed loop sessions</time_frame>
    <description>Blood glucose samples will be obtained from the line approximately every 30 minutes, or every 5-15 minutes at treating physician's discretion, if either the sensor or a previous glucose reading is &lt; 81mg/dL or &gt; 360mg/dL (&lt; 3.5 mmol/l or &gt; 20 mmol/l). Plasma samples will be analyzed using a YSI 2300 Glucose and Lactate Analyzer (YSI, Inc., OH, USA) between 18:00 and 6:00.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>All descriptive endpoints stratified by the accuracy of the sensor based on mean absolute relative difference (MARD) overnight</measure>
    <time_frame>Two overnight closed loop sessions</time_frame>
    <description>A meter blood glucose (BG) value is entered into the Android and a sensor and calibration error check are performed. If the routine determines that the sensor and BG are valid values, the Closed Loop will start.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">9</enrollment>
  <condition>Type 1 Diabetes</condition>
  <arm_group>
    <arm_group_label>Closed Loop Procedure AB</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Closed loop procedure with normal calibration first followed by closed loop procedure B with calibration error induced.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Closed loop Procedure BA</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Closed loop procedure with an induced calibration error first followed by closed loop procedure with normal calibration.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Closed Loop Procedure (Medtronic)</intervention_name>
    <description>The procedure A is the device running under normal conditions, procedure B will incorporate an induced calibration error.</description>
    <arm_group_label>Closed Loop Procedure AB</arm_group_label>
    <arm_group_label>Closed loop Procedure BA</arm_group_label>
    <other_name>AAGC</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  A clinical diagnosis of Type 1 diabetes as determined by the Investigator for a&#xD;
             minimum of 36 months prior to enrollment&#xD;
&#xD;
          -  Weight is between 50 and 120 kg&#xD;
&#xD;
          -  Subject has used a Medtronic insulin pump for at least the previous 6 months&#xD;
&#xD;
          -  Subject has an glycated hemoglobin (A1C) value ≤ 9.0% demonstrated at the time of&#xD;
             enrollment&#xD;
&#xD;
          -  Subject uses a rapid-acting analogue insulin in his/her pump&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Female subject who has a positive serum pregnancy screening test, or who plans to&#xD;
             become pregnant during the course of the study&#xD;
&#xD;
          -  Subject has a history of hypoglycemic seizure or hypoglycemic coma within the past 12&#xD;
             months&#xD;
&#xD;
          -  Subject has an exclusionary cardiac disorder&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>King's College London</name>
      <address>
        <city>London</city>
        <zip>SE5 9PJ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>May 2017</verification_date>
  <study_first_submitted>October 19, 2012</study_first_submitted>
  <study_first_submitted_qc>October 22, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 23, 2012</study_first_posted>
  <last_update_submitted>May 10, 2017</last_update_submitted>
  <last_update_submitted_qc>May 10, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">May 12, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>United Kingdom Overnight closed loop</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/NCT01712594
org study id: CEP223
nct id: NCT01712594
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: Yes
is unapproved device: Yes
is us export: Yes
Currently, patients diagnosed with type 1 diabetes rely on either finger stick or sensor
      glucose readings when making their insulin dosage decisions. Designing a computerized system
      that mimics the way insulin is produced naturally in a person who does not have type 1
      diabetes holds many challenges; all of which cannot be addressed in just one study. The
      purpose of the Medtronic Overnight Closed Loop study is to assess the performance of a system
      designed to automatically infuse the correct insulin dose during the hours that the patient
      is sleeping.

      The system consists of an insulin pump that provides insulin to the patient through an
      infusion set. A sensor inserted just under the patient's skin measures glucose levels and a
      transmitter sends this information to the pump. To enable the sensor to register the glucose
      information correctly, it must be set (calibrated) by a finger stick blood glucose 3-4 times
      a day. In the commercially released system, the physician would recommend the continuous
      background (basal) insulin rates and the patient would be required to make decisions
      regarding extra insulin (bolus) for meals or as a response to high glucose levels.

      In the Closed Loop System, a mobile control system is added to these devices. This consists
      of an Android phone, a closed loop algorithm and a translator. This system is designed to
      translate the sensor information and direct the pump to provide the required dosage of
      insulin automatically without requiring input from the patient.

      Reliable calibration has proved challenging, and so it is important that the system function
      safely, even when calibration is inaccurate. In this study, a calibration error will be
      introduced under very controlled circumstances. This testing will identify if the system can
      maintain acceptable overnight glucose levels, regardless of whether or not calibration is
      ideal.
allocation: Non-Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Amount of time spent in the target range defined as 3.8-8.8 mmol/l (70 to 160 mg/dL) YSI glucose during in-clinic overnight visits
time frame: Two in-patient nights
description: Subjects will arrive at the research facility between 17:00 and 18:00. Plasma glucose will be measured and they will have their evening meal of no more than 80 g of carbohydrate. They will bolus for this meal using their usual Bolus Wizard (Medtronic) settings. After the meal, an IV catheter will be inserted for the collection of venous blood samples. The Mobile Control System will be connected and closed-loop control will be started approximately 4 hours after dinner. The subject will remain under closed-loop control overnight (approximately 11 p.m.-6 a.m.). During one of the Closed Loop nights the system will be challenged by a calibration error of 30%. At approximately 7 am (before breakfast), the Mobile Control System will be turned off and the patient will be provided with a breakfast (approximately 40-70 gm of carbohydrate) and will take a bolus according to the Bolus Wizard. The patient will return to their usual pump treatment with the MiniMed Paradigm Veo System.
measure: Glucose Area under the curve (AUC) below 3.8 mmol/l (70 mg/dL ) YSI glucose obtained during in-clinic overnight visits
time frame: Two overnight closed loop sessions
description: Blood glucose samples will be obtained from the line approximately every 30 minutes, or every 5-15 minutes at treating physician's discretion, if either the sensor or a previous glucose reading is < 81mg/dL or > 360mg/dL (< 3.5 mmol/l or > 20 mmol/l). Plasma samples will be analyzed using a YSI 2300 Glucose and Lactate Analyzer between 18:00 and 6:00.
measure: Glucose AUC above 8.8mmol/l (160 mg/dL) YSI glucose obtained during in-clinic overnight visits
time frame: Two overnight closed loop sessions
description: Blood glucose samples will be obtained from the line approximately every 30 minutes, or every 5-15 minutes at treating physician's discretion, if either the sensor or a previous glucose reading is < 81mg/dL or > 360mg/dL (< 3.5 mmol/l or > 20 mmol/l). Plasma samples will be analyzed using a YSI 2300 Glucose and Lactate Analyzer (YSI, Inc., OH, USA) between 18:00 and 6:00.
measure: All descriptive endpoints stratified by the accuracy of the sensor based on mean absolute relative difference (MARD) overnight
time frame: Two overnight closed loop sessions
description: A meter blood glucose (BG) value is entered into the Android and a sensor and calibration error check are performed. If the routine determines that the sensor and BG are valid values, the Closed Loop will start.
arm group label: Closed Loop Procedure AB
arm group type: Active Comparator
description: Closed loop procedure with normal calibration first followed by closed loop procedure B with calibration error induced.
arm group label: Closed loop Procedure BA
arm group type: Active Comparator
description: Closed loop procedure with an induced calibration error first followed by closed loop procedure with normal calibration.
intervention type: Device
intervention name: Closed Loop Procedure (Medtronic)
description: The procedure A is the device running under normal conditions, procedure B will incorporate an induced calibration error.
arm group label: Closed Loop Procedure AB
arm group label: Closed loop Procedure BA
other name: AAGC
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Diabetes Mellitus, Type 1
sharing ipd: No