Pregnancy Intervention With a Closed-Loop System (PICLS) Study
Condition: Type 1 Diabetes Mellitus; Pregnancy in Diabetes
MeSH terms: Pregnancy in Diabetics; Diabetes Mellitus; Diabetes Mellitus, Type 1
Study type: Interventional

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Hybrid closed-loop therapy; Sensor-augmented pump therapy
Intervention type(s): Device; Device
Intervention description(s): Hybrid closed-loop therapy with a proportional integral derivative (PID) algorithm; Insulin pump + non-communicating CGM
Other intervention name(s): artificial pancreas therapy; SAPT
Intervention MeSH terms: Pancrelipase
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Randomized clinical trial
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: type 1 diabetes mellitus; pregnancy; hybrid closed-loop therapy; artificial pancreas therapy; sensor-augmented pump therapy