<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/NCT03809858</url>
  </required_header>
  <id_info>
    <org_study_id>180034</org_study_id>
    <nct_id>NCT03809858</nct_id>
  </id_info>
  <brief_title>Study to Test Efficacy of Real-time Reminders on Apple Watch To Decrease Late or Missed Meal Boluses</brief_title>
  <official_title>Pilot Study to Test Efficacy of Real-time Reminders on Apple Watch To Decrease Late or Missed Meal Boluses</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Virginia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Stanford University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Klue, Inc.</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Virginia</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 will be a randomized, cross-over, unblinded study with subjects randomized upon entry&#xD;
      into the study to either begin using the Klue software for 6 weeks or to continue with their&#xD;
      usual care for 6 weeks. Subjects are eligible for enrollment if they are using a continuous&#xD;
      glucose monitor (CGM) with an insulin pump or an insulin pen with memory, and are missing or&#xD;
      late in giving at least 4 food boluses in the previous two weeks. Missing or late meal&#xD;
      boluses will be assessed through their pump/pen and sensor downloads. This is a pilot study.&#xD;
      There is no preliminary data to do a true power calculation. The primary outcome will be the&#xD;
      change in the number of missed meal boluses in the two weeks prior to each visit. Secondary&#xD;
      outcome measures will be the number of missed meal boluses in each month of the study, change&#xD;
      in HbA1c levels (measured every 6 weeks), accuracy of the Klue software in detecting meals&#xD;
      (true positive and false positive rates), and a user satisfaction survey.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 29, 2019</start_date>
  <completion_date type="Actual">November 18, 2019</completion_date>
  <primary_completion_date type="Actual">November 18, 2019</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>
    <intervention_model_description>Subjects will be randomized to the sequence of completion in a 1:1 ratio. All subject will collect data throughout the study with half of them using the Klue App during the first 6 weeks and half using the Klue App during the second 6 weeks.</intervention_model_description>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of missed meal boluses</measure>
    <time_frame>During the two weeks prior to each visit</time_frame>
    <description>The change in the number of missed meal boluses</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of missed meal boluses as a measure of attenuation to the alerts</measure>
    <time_frame>6 weeks</time_frame>
    <description>The change in the number of missed meal boluses as a measure of attenuation to the alerts</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of missed meal boluses as a measure of attenuation to the alerts</measure>
    <time_frame>12 weeks</time_frame>
    <description>The change in the number of missed meal boluses as a measure of attenuation to the alerts</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Hemoglobin A1c Levels</measure>
    <time_frame>3 months</time_frame>
    <description>Change in Hemoglobin A1c Levels</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time in range 70-180 mg/dL</measure>
    <time_frame>6 weeks</time_frame>
    <description>Time in range 70-180 mg/dL as measured by CGM</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time in range 70-180 mg/dL</measure>
    <time_frame>12 weeks</time_frame>
    <description>Time in range 70-180 mg/dL as measured by CGM</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent time &lt;70 mg/dL mean glucose</measure>
    <time_frame>6 weeks</time_frame>
    <description>Percent time &lt;70 mg/dL mean glucose as measured by CGM</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent time &lt;70 mg/dL mean glucose</measure>
    <time_frame>12 weeks</time_frame>
    <description>Percent time &lt;70 mg/dL mean glucose as measured by CGM</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Glucose Coefficient of Variation</measure>
    <time_frame>6 weeks</time_frame>
    <description>Glucose (as measured by CGM) Coefficient of Variation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Glucose Coefficient of Variation</measure>
    <time_frame>12 weeks</time_frame>
    <description>Glucose (as measured by CGM) Coefficient of Variation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total daily insulin dose</measure>
    <time_frame>6 weeks</time_frame>
    <description>Total daily insulin dose</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total daily insulin dose</measure>
    <time_frame>12 weeks</time_frame>
    <description>Total daily insulin dose</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of meal bolus injections each day</measure>
    <time_frame>6 weeks</time_frame>
    <description>Number of meal bolus injections each day</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of meal bolus injections each day</measure>
    <time_frame>12 weeks</time_frame>
    <description>Number of meal bolus injections each day</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of total bolus injections each day</measure>
    <time_frame>6 weeks</time_frame>
    <description>Number of total bolus injections each day</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of total bolus injections each day</measure>
    <time_frame>12 weeks</time_frame>
    <description>Number of total bolus injections each day</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total daily basal insulin</measure>
    <time_frame>6 weeks</time_frame>
    <description>Total daily basal insulin</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total daily basal insulin</measure>
    <time_frame>12 weeks</time_frame>
    <description>Total daily basal insulin</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Accuracy of Klue in detecting meals</measure>
    <time_frame>3 months</time_frame>
    <description>Accuracy of Klue in detecting meals (true positive and false positive rates)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>User satisfaction of Klue</measure>
    <time_frame>3 months</time_frame>
    <description>User satisfaction of Klue</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Diabetes-Specific Attitudes about Technology (DSAT) Scores</measure>
    <time_frame>3 months</time_frame>
    <description>DSAT Scores (Scaled from &quot;Strongly Disagree&quot; to &quot;Strongly Agree&quot; in relation to attitudes related to technology in diabetes treatment)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Diabetes Distress Scale (DDS) Scores</measure>
    <time_frame>3 months</time_frame>
    <description>DDS Scores (Scaled from &quot;Not a Problem&quot; to &quot;A Very Serious Problem&quot; in relation to feelings/mood related to diabetes)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Diabetes Mellitus, Type 1</condition>
  <arm_group>
    <arm_group_label>Klue App Use then Usual Care</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will use the Klue App during the first 6 weeks of the trial. At 6 weeks, subjects will discontinue Klue App use and will continue the final 6 weeks without the product.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Usual Care then Klue App Use</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will begin the study without using the Klue App during the first 6 weeks of the trial. At 6 weeks, subjects will begin the use of the Klue App and will continue the final 6 weeks with the product.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Klue App</intervention_name>
    <description>The Klue App utilizes an Apple Watch to detect eating or drinking behavior. The App can initiate a sequence of questions when eating/drinking is detected to determine if a subject has administered a bolus for the meal or if they need to do so.</description>
    <arm_group_label>Klue App Use then Usual Care</arm_group_label>
    <arm_group_label>Usual Care then Klue App Use</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18 and over&#xD;
&#xD;
          -  Using an insulin pump for at least 3 months and currently using CGM or using an&#xD;
             insulin pen with memory and currently using a CGM&#xD;
&#xD;
          -  Willing to wear a CGM at least 70% of the time while in the study&#xD;
&#xD;
          -  Willing to wear an Apple watch on their dominant hand while awake&#xD;
&#xD;
          -  Missing or late in giving at least four food boluses in the previous 2 weeks&#xD;
&#xD;
          -  Understanding and willingness to follow the protocol and sign informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant or lactating women&#xD;
&#xD;
          -  A known medical condition that in the judgement of the investigator might interfere&#xD;
             with the completion of the protocol Note: Adequately treated thyroid disease and&#xD;
             celiac disease do not exclude subjects from enrollment.&#xD;
&#xD;
          -  Current treatment for a seizure disorder&#xD;
&#xD;
          -  Inpatient psychiatric treatment in the past 6 months&#xD;
&#xD;
        Subject may participate in another trial if it is approved by the investigators of both&#xD;
        trials.&#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>Marc Breton, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Virginia</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Virginia</name>
      <address>
        <city>Charlottesville</city>
        <state>Virginia</state>
        <zip>22908</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Burdick J, Chase HP, Slover RH, Knievel K, Scrimgeour L, Maniatis AK, Klingensmith GJ. Missed insulin meal boluses and elevated hemoglobin A1c levels in children receiving insulin pump therapy. Pediatrics. 2004 Mar;113(3 Pt 1):e221-4. doi: 10.1542/peds.113.3.e221.</citation>
    <PMID>14993580</PMID>
  </reference>
  <reference>
    <citation>Olinder AL, Kernell A, Smide B. Missed bolus doses: devastating for metabolic control in CSII-treated adolescents with type 1 diabetes. Pediatr Diabetes. 2009 Apr;10(2):142-8. doi: 10.1111/j.1399-5448.2008.00462.x. Epub 2008 Oct 24.</citation>
    <PMID>19175898</PMID>
  </reference>
  <reference>
    <citation>O'Connell MA, Donath S, Cameron FJ. Poor adherence to integral daily tasks limits the efficacy of CSII in youth. Pediatr Diabetes. 2011 Sep;12(6):556-9. doi: 10.1111/j.1399-5448.2010.00740.x. Epub 2011 Apr 6.</citation>
    <PMID>21466646</PMID>
  </reference>
  <reference>
    <citation>Naranjo D, Tanenbaum ML, Iturralde E, Hood KK. Diabetes Technology: Uptake, Outcomes, Barriers, and the Intersection With Distress. J Diabetes Sci Technol. 2016 Jun 28;10(4):852-8. doi: 10.1177/1932296816650900. Print 2016 Jul.</citation>
    <PMID>27234809</PMID>
  </reference>
  <verification_date>April 2020</verification_date>
  <study_first_submitted>January 11, 2019</study_first_submitted>
  <study_first_submitted_qc>January 15, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 18, 2019</study_first_posted>
  <last_update_submitted>April 18, 2020</last_update_submitted>
  <last_update_submitted_qc>April 18, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">April 21, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Virginia</investigator_affiliation>
    <investigator_full_name>Marc Breton</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>Klue</keyword>
  <keyword>Meal bolus</keyword>
  <keyword>Bolus reminder</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>
    <ipd_description>There is no current plan to share individual participant data</ipd_description>
  </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/NCT03809858
org study id: 180034
nct id: NCT03809858
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This will be a randomized, cross-over, unblinded study with subjects randomized upon entry
      into the study to either begin using the Klue software for 6 weeks or to continue with their
      usual care for 6 weeks. Subjects are eligible for enrollment if they are using a continuous
      glucose monitor (CGM) with an insulin pump or an insulin pen with memory, and are missing or
      late in giving at least 4 food boluses in the previous two weeks. Missing or late meal
      boluses will be assessed through their pump/pen and sensor downloads. This is a pilot study.
      There is no preliminary data to do a true power calculation. The primary outcome will be the
      change in the number of missed meal boluses in the two weeks prior to each visit. Secondary
      outcome measures will be the number of missed meal boluses in each month of the study, change
      in HbA1c levels (measured every 6 weeks), accuracy of the Klue software in detecting meals
      (true positive and false positive rates), and a user satisfaction survey.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: Subjects will be randomized to the sequence of completion in a 1:1 ratio. All subject will collect data throughout the study with half of them using the Klue App during the first 6 weeks and half using the Klue App during the second 6 weeks.
primary purpose: Supportive Care
masking: None (Open Label)
measure: Number of missed meal boluses
time frame: During the two weeks prior to each visit
description: The change in the number of missed meal boluses
measure: Number of missed meal boluses as a measure of attenuation to the alerts
time frame: 6 weeks
description: The change in the number of missed meal boluses as a measure of attenuation to the alerts
measure: Number of missed meal boluses as a measure of attenuation to the alerts
time frame: 12 weeks
description: The change in the number of missed meal boluses as a measure of attenuation to the alerts
measure: Change in Hemoglobin A1c Levels
time frame: 3 months
description: Change in Hemoglobin A1c Levels
measure: Time in range 70-180 mg/dL
time frame: 6 weeks
description: Time in range 70-180 mg/dL as measured by CGM
measure: Time in range 70-180 mg/dL
time frame: 12 weeks
description: Time in range 70-180 mg/dL as measured by CGM
measure: Percent time <70 mg/dL mean glucose
time frame: 6 weeks
description: Percent time <70 mg/dL mean glucose as measured by CGM
measure: Percent time <70 mg/dL mean glucose
time frame: 12 weeks
description: Percent time <70 mg/dL mean glucose as measured by CGM
measure: Glucose Coefficient of Variation
time frame: 6 weeks
description: Glucose (as measured by CGM) Coefficient of Variation
measure: Glucose Coefficient of Variation
time frame: 12 weeks
description: Glucose (as measured by CGM) Coefficient of Variation
measure: Total daily insulin dose
time frame: 6 weeks
description: Total daily insulin dose
measure: Total daily insulin dose
time frame: 12 weeks
description: Total daily insulin dose
measure: Number of meal bolus injections each day
time frame: 6 weeks
description: Number of meal bolus injections each day
measure: Number of meal bolus injections each day
time frame: 12 weeks
description: Number of meal bolus injections each day
measure: Number of total bolus injections each day
time frame: 6 weeks
description: Number of total bolus injections each day
measure: Number of total bolus injections each day
time frame: 12 weeks
description: Number of total bolus injections each day
measure: Total daily basal insulin
time frame: 6 weeks
description: Total daily basal insulin
measure: Total daily basal insulin
time frame: 12 weeks
description: Total daily basal insulin
measure: Accuracy of Klue in detecting meals
time frame: 3 months
description: Accuracy of Klue in detecting meals (true positive and false positive rates)
measure: User satisfaction of Klue
time frame: 3 months
description: User satisfaction of Klue
measure: Diabetes-Specific Attitudes about Technology (DSAT) Scores
time frame: 3 months
description: DSAT Scores (Scaled from "Strongly Disagree" to "Strongly Agree" in relation to attitudes related to technology in diabetes treatment)
measure: Diabetes Distress Scale (DDS) Scores
time frame: 3 months
description: DDS Scores (Scaled from "Not a Problem" to "A Very Serious Problem" in relation to feelings/mood related to diabetes)
arm group label: Klue App Use then Usual Care
arm group type: Experimental
description: Subjects will use the Klue App during the first 6 weeks of the trial. At 6 weeks, subjects will discontinue Klue App use and will continue the final 6 weeks without the product.
arm group label: Usual Care then Klue App Use
arm group type: Experimental
description: Subjects will begin the study without using the Klue App during the first 6 weeks of the trial. At 6 weeks, subjects will begin the use of the Klue App and will continue the final 6 weeks with the product.
intervention type: Other
intervention name: Klue App
description: The Klue App utilizes an Apple Watch to detect eating or drinking behavior. The App can initiate a sequence of questions when eating/drinking is detected to determine if a subject has administered a bolus for the meal or if they need to do so.
arm group label: Klue App Use then Usual Care
arm group label: Usual Care then Klue App Use
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Marc Breton, PhD
role: Principal Investigator
affiliation: University of Virginia
facility: 
country: United States
citation: Burdick J, Chase HP, Slover RH, Knievel K, Scrimgeour L, Maniatis AK, Klingensmith GJ. Missed insulin meal boluses and elevated hemoglobin A1c levels in children receiving insulin pump therapy. Pediatrics. 2004 Mar;113(3 Pt 1):e221-4. doi: 10.1542/peds.113.3.e221.
PMID: 14993580
citation: Olinder AL, Kernell A, Smide B. Missed bolus doses: devastating for metabolic control in CSII-treated adolescents with type 1 diabetes. Pediatr Diabetes. 2009 Apr;10(2):142-8. doi: 10.1111/j.1399-5448.2008.00462.x. Epub 2008 Oct 24.
PMID: 19175898
citation: O'Connell MA, Donath S, Cameron FJ. Poor adherence to integral daily tasks limits the efficacy of CSII in youth. Pediatr Diabetes. 2011 Sep;12(6):556-9. doi: 10.1111/j.1399-5448.2010.00740.x. Epub 2011 Apr 6.
PMID: 21466646
citation: Naranjo D, Tanenbaum ML, Iturralde E, Hood KK. Diabetes Technology: Uptake, Outcomes, Barriers, and the Intersection With Distress. J Diabetes Sci Technol. 2016 Jun 28;10(4):852-8. doi: 10.1177/1932296816650900. Print 2016 Jul.
PMID: 27234809
responsible party type: Principal Investigator
investigator affiliation: University of Virginia
investigator full name: Marc Breton
investigator title: Associate Professor
mesh term: Diabetes Mellitus, Type 1
sharing ipd: No
ipd description: There is no current plan to share individual participant data