Pregnancy Intervention With a Closed-Loop System (PICLS) Study
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Enrollment
- 24
- Locations
- 2
- Primary Endpoint
- Number of Episodes of Severe Hypoglycemia
Study Overview
Brief 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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Single (Outcomes Assessor)
Masking Description
Biostatistician is blinded to intervention assignment
Eligibility Criteria
- Ages
- 18 Years to 45 Years (Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •women with T1D,
- •pregnant within the first 11 weeks of gestation,
- •18 years of age or older,
- •diabetes duration >1 year,
- •using MDI (multiple daily injections) or CSII (continuous subcutaneous insulin infusion) therapy,
- •willingness to routinely check at least 3-7 blood glucose measurements per day,
- •ability and willingness to receive routine and specialty obstetric care throughout the course of the study,
- •ability and willingness to adhere to the protocol including scheduled study visits for the duration of the pregnancy and early post-partum period,
- •A1C 5.5 - 9%,
- •willing to participate in the run-in phase and full study (if eligible), and
- •able to speak, read, and write English
Exclusion Criteria
- •women with T2D, gestational diabetes, or other type of diabetes (e.g., MODY), - -
- •pregnancy beyond gestational week 11 or higher,
- •age <18 years,
- •T1D duration <1 year,
- •screening A1C <5.5% or >9%,
- •use of basal insulin alone,
- •use of bolus insulin alone,
- •extensive skin changes/diseases that inhibit wearing an infusion set, insulin pod, or sensor on normal skin,
- •known severe allergic reaction to device adhesives within the last 3 months,
- •unwillingness to use an insulin pump with tubing,
- •unwillingness to be randomized to study group,
- •unwillingness to switch from MDI to CSII and CGM (continuous glucose monitor) use (if applicable),
- •unwillingness to switch from MDI or to change from current insulin pump to HCL system (if applicable),
- •severe hypoglycemic episode requiring the assistance of a 3rd party within the last 6 months,
- •non-compliance with run-in phase,
- •inadequate access to a phone and computer (for downloading devices and web-based communications),
- •intention to move out of state within the next year, and
- •any other condition determined by the PI which could make the subject unsuitable for the trial or impairs the validity of the informed consent
Arms & Interventions
Sensor-augmented pump therapy (SAPT)
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.
Intervention: Sensor-augmented pump therapy (Device)
Hybrid closed-loop therapy (HCL)
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: Hybrid closed-loop therapy (Device)
Outcomes
Primary Outcomes
Number of Episodes of Severe Hypoglycemia
Time Frame: through study completion, an average of 9 months
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
Time Spent With Glucose <54 mg/dL
Time Frame: Through study completion, an average of 9 months
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
Fear of Hypoglycemia Score
Time Frame: Through study completion, an average of 9 months
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. Score Explanation: Change(s) in behavior and/or concerns of diabetics as detected by the hypoglycemia fear questionnaire. Behavior sub-scale score ranges from 10-50, with higher scores indicating more behavioral changes in the participant's daily routine to avoid low blood sugar. Worry sub-scale score ranges from 17-85, with higher scores indicating more worry or concerns because of low blood sugar. Total score ranges from 27-135, with higher scores for both sub-scales indicating more fear and a worse outcome. Subscales are added for the total scale score. Time Points: Baseline: 9 weeks gestation or earlier Visit 7: 18-20 weeks gestation Visit 10: 30-32 weeks gestation Visit 16: 4-6 weeks after delivery
Indices of Glucose Control: Time Spent in Glucose Ranges by Continuous Glucose Monitoring
Time Frame: Through study completion, an average of 9 months
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
Secondary Outcomes
- Secondary Indices of Glucose Control: J-index(through study completion, an average of 9 months)
- Secondary Indices of Glucose Control: Continuous Overall Net Glycemic Action (CONGAn)(through study completion, an average of 9 months)
- INSPIRE Questionnaire Score(through study completion, an average of 9 months)
- Number of Adverse Skin Reactions(through study completion, an average of 9 months)
- Secondary Indices of Glucose Control: High Blood Glucose Index (HBGI)(through study completion, an average of 9 months)
- Insulin Delivery Satisfaction Survey (IDSS) Score(through study completion, an average of 9 months)
- Number of Episodes of Diabetic Ketoacidosis(Through study completion, an average of 9 months)
- Secondary Indices of Glucose Control: Mean Glucose ± Standard Deviation(through study completion, an average of 9 months)
- Secondary Indices of Glucose Control: Mean Amplitude of Glycemic Excursions (MAGE)(through study completion, an average of 9 months)
- Maternal Outcomes: Average Gestational Weight Gain(through study completion, an average of 9 months)
- Secondary Indices of Glucose Control: Low Blood Glucose Index (LBGI)(through study completion, an average of 9 months)
- Glucose Monitoring Satisfaction Survey (GMSS) Score(through study completion, an average of 9 months)
- Medical Outcomes Study (MOS) Short-Form 36 Score(through study completion, an average of 9 months)
- Maternal Outcomes: Number of Participants With Cesarean Delivery(through study completion, an average of 9 months)
- Fetal Outcomes: Number of Participants With a Fetal Loss (Miscarriage or Stillbirth)(through study completion, an average of 9 months)
- Fetal Outcomes: Number of Participants With Neonatal Hypoglycemia Infants(through study completion, an average of 9 months)
- Maternal Outcomes: Number of Participants With Preeclampsia/Eclampsia(through study completion, an average of 9 months)
- Fetal Outcomes: Number of Infants With Large-for-gestational Age Outcome(through study completion, an average of 9 months)