<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/NCT03774186</url>
  </required_header>
  <id_info>
    <org_study_id>18-1798</org_study_id>
    <nct_id>NCT03774186</nct_id>
  </id_info>
  <brief_title>Pregnancy Intervention With a Closed-Loop System (PICLS) Study</brief_title>
  <acronym>PICLS</acronym>
  <official_title>Pregnancy Intervention With a Closed-Loop System (PICLS) Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Colorado, Denver</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Juvenile Diabetes Research Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Ohio State University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Colorado, Denver</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      In pregnancies associated with diabetes, lowering glucose to the recommended targets to&#xD;
      prevent adverse health outcomes often leads to significant hypoglycemia. Hybrid closed-loop&#xD;
      (HCL) therapy, automated insulin delivery using an insulin pump getting feedback from a&#xD;
      continuous glucose monitor (CGM), may improve outcomes. This exploratory, novel pilot&#xD;
      feasibility randomized clinical trial will evaluate pregnant women with type 1 diabetes (T1D)&#xD;
      on HCL therapy or Sensor-Augmented Pump Therapy (SAPT, non-communicating pump and CGM) from&#xD;
      the 2nd trimester, throughout pregnancy, and 4-6 weeks post-partum. Comparisons will be made&#xD;
      on safety (Specific Aim [SA] 1), indices of glycemic variability and fear of hypoglycemia (SA&#xD;
      2), and quality of life and device satisfaction (SA 3) between groups. Exploratory SA 4 will&#xD;
      compare maternal and fetal outcomes between groups. Safety data will include episodes of&#xD;
      severe hypoglycemia requiring 3rd party assistance, diabetic ketoacidosis, and skin&#xD;
      reactions. Glycemic control will be measured by CGM time spent in glucose ranges (&lt;63,&#xD;
      63-140, &gt;140 mg/dL) and other measures of glycemic variability. Subjects will fill out&#xD;
      surveys (Fear of Hypoglycemia, a quality of life survey, and 2 questionnaires about device&#xD;
      satisfaction) at baseline, throughout gestation, and early post-partum. Data on maternal and&#xD;
      fetal outcomes will be collected. Findings will reveal the safety profile and glucose control&#xD;
      with a novel therapy for pregnant women with type 1 diabetes.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a two-center, prospective, 'open-label', single-blind, investigator-initiated&#xD;
      randomized controlled pilot study evaluating hybrid closed-loop (HCL) insulin delivery among&#xD;
      pregnant women with T1D compared with sensor-augmented pump therapy (SAPT) throughout most of&#xD;
      gestation and the first 6 weeks of the post-partum period at the Barbara Davis Center for&#xD;
      Diabetes and Ohio State University.&#xD;
&#xD;
      Up to 37 women will be enrolled at ≤11 weeks gestation, sign informed consent, and begin a&#xD;
      run-in phase. At baseline, the investigators will obtain data about demographics, health&#xD;
      history, pregnancy history, and medication use. The investigators will conduct a physical&#xD;
      exam, download diabetes devices already in use by subjects, obtain blood and urine tests, and&#xD;
      administer validated questionnaires (Hypoglycemia Fear Survey, MOS Short-Form 36 [SF-26],&#xD;
      INSPIRE Questionnaire, Insulin Delivery Satisfaction Survey [IDSS], and Glucose Monitoring&#xD;
      Satisfaction Survey [GMSS]). During run-in, women will wear a CGM, fill out log sheets&#xD;
      (glucose levels, insulin doses, carbohydrate intake, exercise), upload the CGM, and be in&#xD;
      contact with research staff. Eligible subjects will then be trained on study devices for SAPT&#xD;
      therapy. At the start of the 2nd trimester, women will be randomized to SAPT or HCL therapy.&#xD;
&#xD;
      During pregnancy, women will be seen at each institution monthly for vital signs, HbA1c&#xD;
      measurements, device downloads, pump adjustments, medication use, reporting of adverse events&#xD;
      and device-related deficiencies, and once a trimester the investigators will additionally&#xD;
      obtain serum and urine measurements, specimens for the repository of biological specimens,&#xD;
      and ask subjects to fill out questionnaires (Hypoglycemia Fear Survey, SF-35, IDSS, GMSS).&#xD;
      Weekly remote contact will be obtained for pump adjustments and reporting of adverse events&#xD;
      and device-related deficiencies. Women on HCL therapy will use SAPT during labor and delivery&#xD;
      until 3-7 days post-partum, when a study clinician will put them back into auto mode (HCL&#xD;
      therapy), if it is safe to do so. The final study visit will take place 4-6 weeks post-partum&#xD;
      where the physical exam will be done, HbA1c obtained, device downloads obtained, and final&#xD;
      questionnaires submitted (as above plus a post-partum survey). Medical records of the labor&#xD;
      and delivery admission will be obtained.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">March 21, 2019</start_date>
  <completion_date type="Anticipated">June 1, 2022</completion_date>
  <primary_completion_date type="Anticipated">March 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Randomized clinical trial</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>Biostatistician is blinded to intervention assignment</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Number of episodes of severe hypoglycemia</measure>
    <time_frame>through study completion, an average of 9 months</time_frame>
    <description>Safety of HCL therapy compared to SAPT in women with T1D throughout gestation and the early post-partum period assessed through the number of episodes of severe hypoglycemia requiring 3rd party assistance</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time spent with glucose &lt;54 mg/dL</measure>
    <time_frame>through study completion, an average of 9 months</time_frame>
    <description>Safety of HCL therapy compared to SAPT in women with T1D throughout gestation and the early post-partum period assessed through continuous glucose monitor time spent with glucose &lt;54 mg/dL</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Indices of glucose control: time spent in glucose ranges by continuous glucose monitoring</measure>
    <time_frame>through study completion, an average of 9 months</time_frame>
    <description>Indices of glucose control are time spent in the glucose target ranges &lt;54 mg/dL and &lt;63 mg/dL (hypoglycemia), 63-140 mg/dL (time in range), and &gt;140 mg/dL and &gt;180 mg/dL (hyperglycemia) of HCL compared to SAPT in women with T1D throughout gestation and the first 4-6 weeks post-partum</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Fear of hypoglycemia score</measure>
    <time_frame>through study completion, an average of 9 months</time_frame>
    <description>Fear of hypoglycemia is assessed as behavior, worry, and total scores of fear of hypoglycemia determined by the Hypoglycemia Fear Survey of HCL compared to SAPT in women with T1D throughout gestation and the first 4-6 weeks post-partum. Higher scores indicate more fear.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of episodes of diabetic ketoacidosis</measure>
    <time_frame>through study completionthrough study completion, an average of 9 months</time_frame>
    <description>Secondary safety assessed through the number of episodes of diabetic ketoacidosis of HCL therapy compared to SAPT in women with T1D throughout gestation and the early post-partum period</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of adverse skin reactions</measure>
    <time_frame>through study completion, an average of 9 months</time_frame>
    <description>Secondary safety assessed through the number of adverse skin reactions of HCL therapy compared to SAPT in women with T1D throughout gestation and the early post-partum period</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary indices of glucose control: mean glucose ± standard deviation</measure>
    <time_frame>through study completion, an average of 9 months</time_frame>
    <description>Secondary outcomes of indices of glycemic variability by continuous glucose monitoring as mean glucose ± standard deviation in pregnant women with T1D using HCL or SAPT therapy throughout pregnancy and early post-partum</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary indices of glucose control: J-index</measure>
    <time_frame>through study completion, an average of 9 months</time_frame>
    <description>Secondary outcomes of indices of glycemic variability by continuous glucose monitoring as J index in pregnant women with T1D using HCL or SAPT therapy throughout pregnancy and early post-partum</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary indices of glucose control: High Blood Glucose Index (HBGI)</measure>
    <time_frame>through study completion, an average of 9 months</time_frame>
    <description>Secondary outcomes of indices of glycemic variability by continuous glucose monitoring as High Blood Glucose Index (HBGI) in pregnant women with T1D using HCL or SAPT therapy throughout pregnancy and early post-partum</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary indices of glucose control: Low Blood Glucose Index (LBGI)</measure>
    <time_frame>through study completion, an average of 9 months</time_frame>
    <description>Secondary outcomes of indices of glycemic variability by continuous glucose monitoring as Low Blood Glucose Index (LBGI) in pregnant women with T1D using HCL or SAPT therapy throughout pregnancy and early post-partum</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary indices of glucose control: duration of hypoglycemic episodes</measure>
    <time_frame>through study completion, an average of 9 months</time_frame>
    <description>Secondary outcomes of indices of glycemic variability by continuous glucose monitoring as duration of hypoglycemic episodes in pregnant women with T1D using HCL or SAPT therapy throughout pregnancy and early post-partum</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary indices of glucose control: Mean Amplitude of Glycemic Excursions (MAGE)</measure>
    <time_frame>through study completion, an average of 9 months</time_frame>
    <description>Secondary outcomes of indices of glycemic variability by continuous glucose monitoring as Mean Amplitude of Glycemic Excursions (MAGE) in pregnant women with T1D using HCL or SAPT therapy throughout pregnancy and early post-partum</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary indices of glucose control: Continuous Overall Net Glycemic Action (CONGAn)</measure>
    <time_frame>through study completion, an average of 9 months</time_frame>
    <description>Secondary outcomes of indices of glycemic variability by continuous glucose monitoring as Continuous Overall Net Glycemic Action (CONGAn) in pregnant women with T1D using HCL or SAPT therapy throughout pregnancy and early post-partum</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Medical Outcomes Study (MOS) Short-Form 36 score</measure>
    <time_frame>through study completion, an average of 9 months</time_frame>
    <description>Quality of life as measured by scores from the MOS Short-Form 36 (quality of life) of HCL and SAPT arms in pregnant women with T1D. The SF-36 has eight scaled scores; the scores are weighted sums of the questions in each section. Scores range from 0 - 100 Lower scores = more disability, higher scores = less disability Sections: Vitality, Physical functioning, Bodily pain, General health perceptions, Physical role functioning, Emotional role functioning, Social role functioning, Mental health</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>INSPIRE questionnaire score</measure>
    <time_frame>through study completion, an average of 9 months</time_frame>
    <description>Quality of life as measured by scores from the INSPIRE questionnaire of HCL in pregnant women with T1D</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Insulin Delivery Satisfaction Survey (IDSS) score</measure>
    <time_frame>through study completion, an average of 9 months</time_frame>
    <description>Device acceptability as measured by scores from the Insulin Delivery Satisfaction Survey of HCL and SAPT arms in pregnant women with T1D. The IDSS scale has a total score and 3 subscales: effective, burdensome, and inconvenient</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Glucose Monitoring Satisfaction Survey (GMSS) score</measure>
    <time_frame>through study completion, an average of 9 months</time_frame>
    <description>Device acceptability as measured by scores from the Glucose Monitoring Satisfaction Survey questionnaires of HCL compared to SAPT in pregnancy women with T1D. The GMSS has a total score and 4 subscales: openness, emotional burden, behavioral burden, and trust</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maternal outcomes: rate of preeclampsia/eclampsia</measure>
    <time_frame>through study completion, an average of 9 months</time_frame>
    <description>Maternal outcomes includes preeclampsia/eclampsia in pregnant women with T1D using HCL therapy compared to those using SAPT throughout gestation and in the early post-partum period</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maternal outcomes: rate of cesarean delivery</measure>
    <time_frame>through study completion, an average of 9 months</time_frame>
    <description>Maternal outcomes includes cesarean delivery in pregnant women with T1D using HCL therapy compared to those using SAPT throughout gestation and in the early post-partum period</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maternal outcomes: average gestational weight gain</measure>
    <time_frame>through study completion, an average of 9 months</time_frame>
    <description>Maternal outcomes includes gestational weight gain in pregnant women with T1D using HCL therapy compared to those using SAPT throughout gestation and in the early post-partum period</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fetal outcomes: rate of fetal loss (miscarriage or stillbirth)</measure>
    <time_frame>through study completion, an average of 9 months</time_frame>
    <description>Fetal outcomes includes fetal loss (miscarriage or stillbirth) in pregnant women with T1D using HCL therapy compared to those using SAPT throughout gestation and in the early post-partum period</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fetal outcomes: rate of large-for-gestational age infants</measure>
    <time_frame>through study completion, an average of 9 months</time_frame>
    <description>Fetal outcomes includes large-for-gestational age in pregnant women with T1D using HCL therapy compared to those using SAPT throughout gestation and in the early post-partum period</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fetal outcomes: rate of neonatal hypoglycemia</measure>
    <time_frame>through study completion, an average of 9 months</time_frame>
    <description>Fetal outcomes includes neonatal hypoglycemia in pregnant women with T1D using HCL therapy compared to those using SAPT throughout gestation and in the early post-partum period</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">47</enrollment>
  <condition>Type 1 Diabetes Mellitus</condition>
  <condition>Pregnancy in Diabetes</condition>
  <arm_group>
    <arm_group_label>Sensor-augmented pump therapy (SAPT)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Pregnant women with T1D with use an insulin pump and a continuous glucose monitor but there will be no automated insulin adjustments made by the system.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Hybrid closed-loop therapy (HCL)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Pregnant women with T1D with use an insulin pump and a continuous glucose monitor with automated insulin adjustments made by the system, but continued meal boluses from the women.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Hybrid closed-loop therapy</intervention_name>
    <description>Hybrid closed-loop therapy with a proportional integral derivative (PID) algorithm</description>
    <arm_group_label>Hybrid closed-loop therapy (HCL)</arm_group_label>
    <other_name>artificial pancreas therapy</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Sensor-augmented pump therapy</intervention_name>
    <description>Insulin pump + non-communicating CGM</description>
    <arm_group_label>Sensor-augmented pump therapy (SAPT)</arm_group_label>
    <other_name>SAPT</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  women with T1D,&#xD;
&#xD;
          -  pregnant within the first 11 weeks of gestation,&#xD;
&#xD;
          -  18 years of age or older,&#xD;
&#xD;
          -  diabetes duration &gt;1 year,&#xD;
&#xD;
          -  using MDI (multiple daily injections) or CSII (continuous subcutaneous insulin&#xD;
             infusion) therapy,&#xD;
&#xD;
          -  willingness to routinely check at least 3-7 blood glucose measurements per day,&#xD;
&#xD;
          -  ability and willingness to receive routine and specialty obstetric care throughout the&#xD;
             course of the study,&#xD;
&#xD;
          -  ability and willingness to adhere to the protocol including scheduled study visits for&#xD;
             the duration of the pregnancy and early post-partum period,&#xD;
&#xD;
          -  A1C 5.5 - 9%,&#xD;
&#xD;
          -  willing to participate in the run-in phase and full study (if eligible), and&#xD;
&#xD;
          -  able to speak, read, and write English&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  women with T2D, gestational diabetes, or other type of diabetes (e.g., MODY), - -&#xD;
&#xD;
          -  pregnancy beyond gestational week 11 or higher,&#xD;
&#xD;
          -  age &lt;18 years,&#xD;
&#xD;
          -  T1D duration &lt;1 year,&#xD;
&#xD;
          -  screening A1C &lt;5.5% or &gt;9%,&#xD;
&#xD;
          -  use of basal insulin alone,&#xD;
&#xD;
          -  use of bolus insulin alone,&#xD;
&#xD;
          -  extensive skin changes/diseases that inhibit wearing an infusion set, insulin pod, or&#xD;
             sensor on normal skin,&#xD;
&#xD;
          -  known severe allergic reaction to device adhesives within the last 3 months,&#xD;
&#xD;
          -  unwillingness to use an insulin pump with tubing,&#xD;
&#xD;
          -  unwillingness to be randomized to study group,&#xD;
&#xD;
          -  unwillingness to switch from MDI to CSII and CGM (continuous glucose monitor) use (if&#xD;
             applicable),&#xD;
&#xD;
          -  unwillingness to switch from MDI or to change from current insulin pump to HCL system&#xD;
             (if applicable),&#xD;
&#xD;
          -  severe hypoglycemic episode requiring the assistance of a 3rd party within the last 6&#xD;
             months,&#xD;
&#xD;
          -  non-compliance with run-in phase,&#xD;
&#xD;
          -  inadequate access to a phone and computer (for downloading devices and web-based&#xD;
             communications),&#xD;
&#xD;
          -  intention to move out of state within the next year, and&#xD;
&#xD;
          -  any other condition determined by the PI which could make the subject unsuitable for&#xD;
             the trial or impairs the validity of the informed consent&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sarit Polsky, MD, MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>Regents of the University of Colorado</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Colorado</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ohio State University Wexner Medical Center</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>December 5, 2018</study_first_submitted>
  <study_first_submitted_qc>December 10, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 12, 2018</study_first_posted>
  <last_update_submitted>October 11, 2021</last_update_submitted>
  <last_update_submitted_qc>October 11, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 13, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>type 1 diabetes mellitus</keyword>
  <keyword>pregnancy</keyword>
  <keyword>hybrid closed-loop therapy</keyword>
  <keyword>artificial pancreas therapy</keyword>
  <keyword>sensor-augmented pump therapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pregnancy in Diabetics</mesh_term>
    <mesh_term>Diabetes Mellitus</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 1</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pancrelipase</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>August 9, 2023</submitted>
    <returned>September 1, 2023</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/NCT03774186
org study id: 18-1798
nct id: NCT03774186
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
In pregnancies associated with diabetes, lowering glucose to the recommended targets to
      prevent adverse health outcomes often leads to significant hypoglycemia. Hybrid closed-loop
      (HCL) therapy, automated insulin delivery using an insulin pump getting feedback from a
      continuous glucose monitor (CGM), may improve outcomes. This exploratory, novel pilot
      feasibility randomized clinical trial will evaluate pregnant women with type 1 diabetes (T1D)
      on HCL therapy or Sensor-Augmented Pump Therapy (SAPT, non-communicating pump and CGM) from
      the 2nd trimester, throughout pregnancy, and 4-6 weeks post-partum. Comparisons will be made
      on safety (Specific Aim [SA] 1), indices of glycemic variability and fear of hypoglycemia (SA
      2), and quality of life and device satisfaction (SA 3) between groups. Exploratory SA 4 will
      compare maternal and fetal outcomes between groups. Safety data will include episodes of
      severe hypoglycemia requiring 3rd party assistance, diabetic ketoacidosis, and skin
      reactions. Glycemic control will be measured by CGM time spent in glucose ranges (<63,
      63-140, >140 mg/dL) and other measures of glycemic variability. Subjects will fill out
      surveys (Fear of Hypoglycemia, a quality of life survey, and 2 questionnaires about device
      satisfaction) at baseline, throughout gestation, and early post-partum. Data on maternal and
      fetal outcomes will be collected. Findings will reveal the safety profile and glucose control
      with a novel therapy for pregnant women with type 1 diabetes.
This is a two-center, prospective, 'open-label', single-blind, investigator-initiated
      randomized controlled pilot study evaluating hybrid closed-loop (HCL) insulin delivery among
      pregnant women with T1D compared with sensor-augmented pump therapy (SAPT) throughout most of
      gestation and the first 6 weeks of the post-partum period at the Barbara Davis Center for
      Diabetes and Ohio State University.

      Up to 37 women will be enrolled at ≤11 weeks gestation, sign informed consent, and begin a
      run-in phase. At baseline, the investigators will obtain data about demographics, health
      history, pregnancy history, and medication use. The investigators will conduct a physical
      exam, download diabetes devices already in use by subjects, obtain blood and urine tests, and
      administer validated questionnaires (Hypoglycemia Fear Survey, MOS Short-Form 36 [SF-26],
      INSPIRE Questionnaire, Insulin Delivery Satisfaction Survey [IDSS], and Glucose Monitoring
      Satisfaction Survey [GMSS]). During run-in, women will wear a CGM, fill out log sheets
      (glucose levels, insulin doses, carbohydrate intake, exercise), upload the CGM, and be in
      contact with research staff. Eligible subjects will then be trained on study devices for SAPT
      therapy. At the start of the 2nd trimester, women will be randomized to SAPT or HCL therapy.

      During pregnancy, women will be seen at each institution monthly for vital signs, HbA1c
      measurements, device downloads, pump adjustments, medication use, reporting of adverse events
      and device-related deficiencies, and once a trimester the investigators will additionally
      obtain serum and urine measurements, specimens for the repository of biological specimens,
      and ask subjects to fill out questionnaires (Hypoglycemia Fear Survey, SF-35, IDSS, GMSS).
      Weekly remote contact will be obtained for pump adjustments and reporting of adverse events
      and device-related deficiencies. Women on HCL therapy will use SAPT during labor and delivery
      until 3-7 days post-partum, when a study clinician will put them back into auto mode (HCL
      therapy), if it is safe to do so. The final study visit will take place 4-6 weeks post-partum
      where the physical exam will be done, HbA1c obtained, device downloads obtained, and final
      questionnaires submitted (as above plus a post-partum survey). Medical records of the labor
      and delivery admission will be obtained.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomized clinical trial
primary purpose: Treatment
masking: Single (Outcomes Assessor)
masking description: Biostatistician is blinded to intervention assignment
measure: Number of episodes of severe hypoglycemia
time frame: through study completion, an average of 9 months
description: Safety of HCL therapy compared to SAPT in women with T1D throughout gestation and the early post-partum period assessed through the number of episodes of severe hypoglycemia requiring 3rd party assistance
measure: Time spent with glucose <54 mg/dL
time frame: through study completion, an average of 9 months
description: Safety of HCL therapy compared to SAPT in women with T1D throughout gestation and the early post-partum period assessed through continuous glucose monitor time spent with glucose <54 mg/dL
measure: Indices of glucose control: time spent in glucose ranges by continuous glucose monitoring
time frame: through study completion, an average of 9 months
description: Indices of glucose control are time spent in the glucose target ranges <54 mg/dL and <63 mg/dL (hypoglycemia), 63-140 mg/dL (time in range), and >140 mg/dL and >180 mg/dL (hyperglycemia) of HCL compared to SAPT in women with T1D throughout gestation and the first 4-6 weeks post-partum
measure: Fear of hypoglycemia score
time frame: through study completion, an average of 9 months
description: Fear of hypoglycemia is assessed as behavior, worry, and total scores of fear of hypoglycemia determined by the Hypoglycemia Fear Survey of HCL compared to SAPT in women with T1D throughout gestation and the first 4-6 weeks post-partum. Higher scores indicate more fear.
measure: Number of episodes of diabetic ketoacidosis
time frame: through study completionthrough study completion, an average of 9 months
description: Secondary safety assessed through the number of episodes of diabetic ketoacidosis of HCL therapy compared to SAPT in women with T1D throughout gestation and the early post-partum period
measure: Number of adverse skin reactions
time frame: through study completion, an average of 9 months
description: Secondary safety assessed through the number of adverse skin reactions of HCL therapy compared to SAPT in women with T1D throughout gestation and the early post-partum period
measure: Secondary indices of glucose control: mean glucose ± standard deviation
time frame: through study completion, an average of 9 months
description: Secondary outcomes of indices of glycemic variability by continuous glucose monitoring as mean glucose ± standard deviation in pregnant women with T1D using HCL or SAPT therapy throughout pregnancy and early post-partum
measure: Secondary indices of glucose control: J-index
time frame: through study completion, an average of 9 months
description: Secondary outcomes of indices of glycemic variability by continuous glucose monitoring as J index in pregnant women with T1D using HCL or SAPT therapy throughout pregnancy and early post-partum
measure: Secondary indices of glucose control: High Blood Glucose Index (HBGI)
time frame: through study completion, an average of 9 months
description: Secondary outcomes of indices of glycemic variability by continuous glucose monitoring as High Blood Glucose Index (HBGI) in pregnant women with T1D using HCL or SAPT therapy throughout pregnancy and early post-partum
measure: Secondary indices of glucose control: Low Blood Glucose Index (LBGI)
time frame: through study completion, an average of 9 months
description: Secondary outcomes of indices of glycemic variability by continuous glucose monitoring as Low Blood Glucose Index (LBGI) in pregnant women with T1D using HCL or SAPT therapy throughout pregnancy and early post-partum
measure: Secondary indices of glucose control: duration of hypoglycemic episodes
time frame: through study completion, an average of 9 months
description: Secondary outcomes of indices of glycemic variability by continuous glucose monitoring as duration of hypoglycemic episodes in pregnant women with T1D using HCL or SAPT therapy throughout pregnancy and early post-partum
measure: Secondary indices of glucose control: Mean Amplitude of Glycemic Excursions (MAGE)
time frame: through study completion, an average of 9 months
description: Secondary outcomes of indices of glycemic variability by continuous glucose monitoring as Mean Amplitude of Glycemic Excursions (MAGE) in pregnant women with T1D using HCL or SAPT therapy throughout pregnancy and early post-partum
measure: Secondary indices of glucose control: Continuous Overall Net Glycemic Action (CONGAn)
time frame: through study completion, an average of 9 months
description: Secondary outcomes of indices of glycemic variability by continuous glucose monitoring as Continuous Overall Net Glycemic Action (CONGAn) in pregnant women with T1D using HCL or SAPT therapy throughout pregnancy and early post-partum
measure: Medical Outcomes Study (MOS) Short-Form 36 score
time frame: through study completion, an average of 9 months
description: Quality of life as measured by scores from the MOS Short-Form 36 (quality of life) of HCL and SAPT arms in pregnant women with T1D. The SF-36 has eight scaled scores; the scores are weighted sums of the questions in each section. Scores range from 0 - 100 Lower scores = more disability, higher scores = less disability Sections: Vitality, Physical functioning, Bodily pain, General health perceptions, Physical role functioning, Emotional role functioning, Social role functioning, Mental health
measure: INSPIRE questionnaire score
time frame: through study completion, an average of 9 months
description: Quality of life as measured by scores from the INSPIRE questionnaire of HCL in pregnant women with T1D
measure: Insulin Delivery Satisfaction Survey (IDSS) score
time frame: through study completion, an average of 9 months
description: Device acceptability as measured by scores from the Insulin Delivery Satisfaction Survey of HCL and SAPT arms in pregnant women with T1D. The IDSS scale has a total score and 3 subscales: effective, burdensome, and inconvenient
measure: Glucose Monitoring Satisfaction Survey (GMSS) score
time frame: through study completion, an average of 9 months
description: Device acceptability as measured by scores from the Glucose Monitoring Satisfaction Survey questionnaires of HCL compared to SAPT in pregnancy women with T1D. The GMSS has a total score and 4 subscales: openness, emotional burden, behavioral burden, and trust
measure: Maternal outcomes: rate of preeclampsia/eclampsia
time frame: through study completion, an average of 9 months
description: Maternal outcomes includes preeclampsia/eclampsia in pregnant women with T1D using HCL therapy compared to those using SAPT throughout gestation and in the early post-partum period
measure: Maternal outcomes: rate of cesarean delivery
time frame: through study completion, an average of 9 months
description: Maternal outcomes includes cesarean delivery in pregnant women with T1D using HCL therapy compared to those using SAPT throughout gestation and in the early post-partum period
measure: Maternal outcomes: average gestational weight gain
time frame: through study completion, an average of 9 months
description: Maternal outcomes includes gestational weight gain in pregnant women with T1D using HCL therapy compared to those using SAPT throughout gestation and in the early post-partum period
measure: Fetal outcomes: rate of fetal loss (miscarriage or stillbirth)
time frame: through study completion, an average of 9 months
description: Fetal outcomes includes fetal loss (miscarriage or stillbirth) in pregnant women with T1D using HCL therapy compared to those using SAPT throughout gestation and in the early post-partum period
measure: Fetal outcomes: rate of large-for-gestational age infants
time frame: through study completion, an average of 9 months
description: Fetal outcomes includes large-for-gestational age in pregnant women with T1D using HCL therapy compared to those using SAPT throughout gestation and in the early post-partum period
measure: Fetal outcomes: rate of neonatal hypoglycemia
time frame: through study completion, an average of 9 months
description: Fetal outcomes includes neonatal hypoglycemia in pregnant women with T1D using HCL therapy compared to those using SAPT throughout gestation and in the early post-partum period
arm group label: Sensor-augmented pump therapy (SAPT)
arm group type: Active Comparator
description: Pregnant women with T1D with use an insulin pump and a continuous glucose monitor but there will be no automated insulin adjustments made by the system.
arm group label: Hybrid closed-loop therapy (HCL)
arm group type: Experimental
description: Pregnant women with T1D with use an insulin pump and a continuous glucose monitor with automated insulin adjustments made by the system, but continued meal boluses from the women.
intervention type: Device
intervention name: Hybrid closed-loop therapy
description: Hybrid closed-loop therapy with a proportional integral derivative (PID) algorithm
arm group label: Hybrid closed-loop therapy (HCL)
other name: artificial pancreas therapy
intervention type: Device
intervention name: Sensor-augmented pump therapy
description: Insulin pump + non-communicating CGM
arm group label: Sensor-augmented pump therapy (SAPT)
other name: SAPT
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: No
last name: Sarit Polsky, MD, MPH
role: Principal Investigator
affiliation: Regents of the University of Colorado
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Pregnancy in Diabetics
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 1
mesh term: Pancrelipase
sharing ipd: No
submitted: August 9, 2023
returned: September 1, 2023