Closed-loop Insulin Delivery in Pregnant Women With Type 1 Diabetes

Study Overview
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Brief Summary
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Multi-centric open-label randomized controlled trial (RCT) with 11 Belgian centers and one Dutch center in pregnant women with type 1 diabetes to assess safety, efficacy, feasibility and cost-effectiveness of 780 MiniMed Medtronic hybrid closed-loop insulin system (intervention group) compared to standard of care therapy (control group).

Detailed Description
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Women will be recruited with a singleton pregnancy up to 12 weeks gestation. Participants will be randomized 1/1 to 780 pump or standard of care (continue with current treatment of insulin pump without closed-loop or multiple daily insulin injections). Participants will be stratified according to study center, baseline Hba1c, and method of insulin delivery (pump or injections). Participants will be followed-up till delivery. To account for differences in the type of continuous glucose monitoring (CGM) used between the intervention group and the control group, the same CGM system as in the 780 insulin pump group (Guardian™ Sensor 3 and once available the Guardian 4 sensor) will be used in a blinded manner in the control group to collect CGM data during at least four different time points in pregnancy: at 14-17 weeks, 20-23 weeks, 26-29 weeks and 33-36 weeks.

Official Title
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Closed-loop Insulin Delivery in Pregnant Women With Type 1 Diabetes: a Randomized Controlled Trial: the CRISTAL Study

Conditions
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Type1 Diabetes

Intervention / Treatment
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* Device: 780G
* Device: standard of care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women with type 1 diabetes (T1DM), diagnosed with T1DM at least 1 year before pregnancy Age 18-45 years A singleton pregnancy confirmed by b-HCG in blood and/or ultrasound-confirmed gestational age up to 11 weeks and 6 days. Treated with intensive insulin treatment (either MDI or insulin pump). A closed-loop system can only be used in manual mode. Have a booking HbA1c (measurement taken at the first antenatal clinic visit after confirmed pregnancy) level ≤10%. Participants need to speak and understand Flemish, French or English and have e-mail access. Exclusion Criteria: The use of a closed-loop insulin delivery system in auto mode. A twin (multiple) pregnancy A physical or psychological disease likely to interfere with the conduct of the study (based on the evaluation by the treating physician) Medications known to interfere with glucose metabolism An insulin dose of ≥1.5 units/kg Known allergy to adhesives due to infusion set and/or CGM

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 1/1 randomization to 780G or continue with standard of care
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 780G closed-loop<br>780 closed-loop insulin delivery system | Device: 780G<br>* 780G closed-loop insulin delivery system (Medtronic)<br>|
| Active Comparator: standard of care<br>standard of care treatment (continue with current treatment of insulin pump without closed-loop or multiple daily insulin injections). | Device: standard of care<br>* continue with standard of care treatment (pump without closed-loop or MDI)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| time in range | time between 63-140mg/dl (pregnancy glycemic target range) | from 14 weeks to 36 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| time in range during the night | time in range (63-140mg/dl) from midnight till 6am | from 14 weeks to 36 weeks | 
| time below low day and night | time <63mg/dl day and night | from 14 weeks to 36 weeks | 
| overnight time low | time <63mg/dl from midnight till 6am | from 14 weeks to 36 weeks | 
| time in range during the day | time in range (63-140mg/dl) during the day | from 14 weeks to 36 weeks | 
| time in range early pregnancy | time in range (63-140mg/dl) 9-12 weeks | from 9 weeks to 12 weeks | 
| time in range during each trimester | time in range (63-140mg/dl) during each trimester | from 9 weeks to 36 weeks | 
| HbA1c during each trimester | HbA1c (% and mmol/mol) during each trimester | from 9 weeks to 36 weeks | 
| mean glucose | mean glucose based on CGM | from 14 weeks to 36 weeks | 
| time above target (140mg/dl) | time >140mg/dl | from 14 weeks to 36 weeks | 
| time above target (180mg/dl) | time >180mg/dl | from 14 weeks to 36 weeks | 
| time below target (50mg/dl) | time <50mg/dl | from 14 weeks to 36 weeks | 
| time below target (54mg/dl) | time <54mg/dl | from 14 weeks to 36 weeks | 
| duration of hypoglycemia | low blood glucose index | from 14 weeks to 36 weeks | 
| time in nonpregnant target range | time 70-180mg/dl | from 14 weeks to 36 weeks | 
| CGM compliance | % of time use of CGM | from 14 weeks to 36 weeks | 
| insulin dose | total insulin dose | from 14 weeks to 36 weeks | 
| glycemic variability | standard deviation glucose values based on CGM | from 14 weeks to 36 weeks | 
| variation glucose values | coefficient of variation based on CGM | from 14 weeks to 36 weeks | 
| MAGE | mean amplitude of glucose variations based on CGM | from 14 weeks to 36 weeks | 
| nocturnal hypoglycemia | glucose <50mg/dl from 23-07hour | from 9 weeks to 36 weeks | 
| severe hypoglycemia | hypoglycemia requiring third-part assistance | from 9 weeks to 36 weeks | 
| rate of diabetic keto-acidosis | metabolic keto-acidosis with decreased ph and/or decreased bicarbonate in blood | from 9 weeks to 36 weeks | 
| gestational duration | duration of pregnancy (weeks) | delivery | 
| duration hospitalization delivery | length of hospital stay (days) | delivery | 
| type of labor | spontaneous, induced or cesarean section before labor | delivery | 
| type of delivery | vaginal, forceps or vacuum, cesarean section during labor or planned cesarean section | delivery | 
| rate of preterm delivery | delivery <37 weeks | delivery | 
| rate of gestational hypertension | blood pressure of 140/90mmHg or higher starting after 20 weeks of gestation | from 20 weeks to delivery | 
| rate of worsening of chronic hypertension | blood pressure of 140/90mmHg or higher start is present before 20 weeks of gestation | from 9 weeks to delivery | 
| rate of preeclampsia | onset of new hypertension and proteinuria and/or end-organ dysfunction after 20 weeks of gestation | from 20 weeks to delivery | 
| rate of eclampsia | generalized convulsions and/or coma | from 20 weeks to delivery | 
| rate of HELLP syndrome | hemolysis, elevated liver enzymes and a low platelet count | from 20 weeks to delivery | 
| rate of IUGR | intra-uterine growth restriction | from 20 weeks to delivery | 
| rate of fetal malformation | congenital malformation | up to 24 weeks | 
| rate of miscarriage | fetal loss <20 weeks gestations | <20 weeks | 
| rate of termination of pregnancy | induced abortion | up to 24 weeks | 
| rate of stillbirth | mors in utero >20 weeks | >20 weeks | 
| rate of neonatal death | death <1 months after delivery | 1 month after delivery | 
| sex of infant | boy or girl | delivery | 
| birth weight | birth weight (Kg and g) | delivery | 
| rate of shoulder dystocia | one or both of a baby's shoulders get stuck inside the mother's pelvis during labor. | delivery | 
| rate of birth trauma | fracture, damage to nerves... | delivery | 
| rate of respiratory distress | respiratory failure or distress | delivery | 
| rate of hyperbilirubinaemia | hyperbilirubinaemia with need of treatment with phototherapy | delivery | 
| rate of macrosomia | birth weight >4Kg | delivery | 
| rate with high birth weight | birth weight >4.5Kg | delivery | 
| rate of LGA infant (lage for gestational age) | gestational age adjusted birth weight >90th percentile according to the standardized Flemish birth charts adjusted for parity and sex | delivery | 
| rate of SGA infant (small for gestational age) | gestational age adjusted birth weight <10th percentile according to the standardized Flemish birth charts adjusted for parity and sex | delivery | 
| number with very large gestational age infants | gestational age adjusted birth weight >97th percentile according to the standardized Flemish birth charts adjusted for parity and sex | delivery | 
| cord blood ph | cord blood gas ph | delivery | 
| rate of neonatal hypoglycemia | neonatal hypoglycemia requiring intravenous dextrose | up to 5 days after delivery | 
| rate of NICU admission | Neonatal intensive care unit (NICU) admission defined as requiring a duration of at least 24 h | up to 30 days after delivery | 
| duration NICU admission | duration of NICU admission (days or weeks) | up to 30 days after delivery | 
| rate of fetal hyperinsulinemia | cord blood c-peptide | delivery | 
| skinfolds newborn | sum of skinfolds (triceps, scapula and flank) | up to 3 days after delivery | 
| neonatal fat mass | fat mass calculated by the formula of Catalano | up to 3 days after delivery | 
| number with composite neonatal outcome | pregnancy loss (miscarriage, still birth or neonatal death), LGA, respiratory distress syndrome, birth trauma, shoulder dystocia, neonatal hypoglycemia and NICU admission | delivery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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closed-loop insulin delivery