Clinical trial NCT04520971: Closed-loop Insulin Delivery in Pregnant Women With Type 1 Diabetes
Official title: Closed-loop Insulin Delivery in Pregnant Women With Type 1 Diabetes: a Randomized Controlled Trial: the CRISTAL Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type1 Diabetes
Keywords: closed-loop insulin delivery
Lead sponsor: Universitaire Ziekenhuizen KU Leuven
Sponsor class: OTHER
Collaborators: name: University Hospital, Ghent
name: Universitair Ziekenhuis Brussel
name: University Hospital, Antwerp
name: Imelda Hospital, Bonheiden
name: AZ Sint-Jan AV
name: AZ Delta
name: Onze Lieve Vrouw Hospital
name: General Hospital Groeninge
name: AZ Nikolaas
name: AZ Turnhout
name: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
name: Amsterdam UMC
First posted: 2020-08-20
Enrollment: 95
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 1/1 randomization to 780G or continue with standard of care
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: time in range
timeFrame: from 14 weeks to 36 weeks
Secondary outcomes:
measure: time in range during the night
timeFrame: from 14 weeks to 36 weeks
measure: time below low day and night
timeFrame: from 14 weeks to 36 weeks
measure: overnight time low
timeFrame: from 14 weeks to 36 weeks
measure: time in range during the day
timeFrame: from 14 weeks to 36 weeks
measure: time in range early pregnancy
timeFrame: from 9 weeks to 12 weeks
measure: time in range during each trimester
timeFrame: from 9 weeks to 36 weeks
measure: HbA1c during each trimester
timeFrame: from 9 weeks to 36 weeks
measure: mean glucose
timeFrame: from 14 weeks to 36 weeks
measure: time above target (140mg/dl)
timeFrame: from 14 weeks to 36 weeks
measure: time above target (180mg/dl)
timeFrame: from 14 weeks to 36 weeks
measure: time below target (50mg/dl)
timeFrame: from 14 weeks to 36 weeks
measure: time below target (54mg/dl)
timeFrame: from 14 weeks to 36 weeks
measure: duration of hypoglycemia
timeFrame: from 14 weeks to 36 weeks
measure: time in nonpregnant target range
timeFrame: from 14 weeks to 36 weeks
measure: CGM compliance
timeFrame: from 14 weeks to 36 weeks
measure: insulin dose
timeFrame: from 14 weeks to 36 weeks
measure: glycemic variability
timeFrame: from 14 weeks to 36 weeks
measure: variation glucose values
timeFrame: from 14 weeks to 36 weeks
measure: MAGE (mean amplitude of glycemic excursions)
timeFrame: from 14 weeks to 36 weeks
measure: nocturnal hypoglycemia
timeFrame: from 9 weeks to 36 weeks
measure: severe hypoglycemia
timeFrame: from 9 weeks to 36 weeks
measure: rate of diabetic keto-acidosis
timeFrame: from 9 weeks to 36 weeks
measure: gestational duration
timeFrame: delivery
measure: duration hospitalization delivery
timeFrame: delivery
measure: type of labor
timeFrame: delivery
measure: type of delivery
timeFrame: delivery
measure: rate of preterm delivery
timeFrame: delivery
measure: rate of gestational hypertension
timeFrame: from 20 weeks to delivery
measure: rate of worsening of chronic hypertension
timeFrame: from 9 weeks to delivery
measure: rate of preeclampsia
timeFrame: from 20 weeks to delivery
measure: rate of eclampsia
timeFrame: from 20 weeks to delivery
measure: rate of HELLP syndrome
timeFrame: from 20 weeks to delivery
measure: rate of IUGR (intra-uterine growth restriction)
timeFrame: from 20 weeks to delivery
measure: rate of fetal malformation
timeFrame: up to 24 weeks
measure: rate of miscarriage
timeFrame: <20 weeks
measure: rate of termination of pregnancy
timeFrame: up to 24 weeks
measure: rate of stillbirth
timeFrame: >20 weeks
measure: rate of neonatal death
timeFrame: 1 month after delivery
measure: sex of infant
timeFrame: delivery
measure: birth weight
timeFrame: delivery
measure: rate of shoulder dystocia
timeFrame: delivery
measure: rate of birth trauma
timeFrame: delivery
measure: rate of respiratory distress
timeFrame: delivery
measure: rate of hyperbilirubinaemia
timeFrame: delivery
measure: rate of macrosomia
timeFrame: delivery
measure: rate with high birth weight
timeFrame: delivery
measure: rate of LGA infant (large for gestational age)
timeFrame: delivery
measure: rate of SGA infant (small for gestational age)
timeFrame: delivery
measure: number with very large gestational age infants
timeFrame: delivery
measure: cord blood ph
timeFrame: delivery
measure: rate of neonatal hypoglycemia
timeFrame: up to 5 days after delivery
measure: rate of NICU admission
timeFrame: up to 30 days after delivery
measure: duration NICU admission
timeFrame: up to 30 days after delivery
measure: rate of fetal hyperinsulinemia
timeFrame: delivery
measure: skinfolds newborn
timeFrame: up to 3 days after delivery
measure: neonatal fat mass
timeFrame: up to 3 days after delivery
measure: number with composite neonatal outcome
timeFrame: delivery
Other outcomes:
Locations:
city: Aalst
country: Belgium
facility: OLV Aalst-Asse
state: Oost-Vlaanderen
city: Bonheiden
country: Belgium
facility: Imelda Bonheiden
city: Brugge
country: Belgium
facility: AZ St Jan Brugge
city: Brussels
country: Belgium
facility: UCLouvain
city: Brussel
country: Belgium
facility: UZ Brussel
city: Gent
country: Belgium
facility: UZ Gent
city: Kortrijk
country: Belgium
facility: AZ Groeninge Kortrijk
city: Leuven
country: Belgium
facility: UZ Leuven
city: Roeselare
country: Belgium
facility: AZ Roeselare
city: Sint-Niklaas
country: Belgium
facility: AZ Nikolaas
city: Turnhout
country: Belgium
facility: AZ Turnhout
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC
Study officials:
affiliation: UZ Leuven
name: Katrien Benhalima, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Beunen K, Van Wilder N, Ballaux D, Vanhaverbeke G, Taes Y, Aers XP, Nobels F, Marlier J, Lee D, Cuypers J, Preumont V, Siegelaar SE, Painter RC, Laenen A, Gillard P, Mathieu C, Benhalima K. Closed-loop insulin delivery in pregnant women with type 1 diabetes (CRISTAL): a multicentre randomized controlled trial - study protocol. BMC Pregnancy Childbirth. 2023 Mar 16;23(1):180. doi: 10.1186/s12884-023-05481-0.
citation: Benhalima K, Beunen K, Van Wilder N, Ballaux D, Vanhaverbeke G, Taes Y, Aers XP, Nobels F, Marlier J, Lee D, Cuypers J, Preumont V, Siegelaar SE, Painter RC, Laenen A, Gillard P, Mathieu C. Comparing advanced hybrid closed loop therapy and standard insulin therapy in pregnant women with type 1 diabetes (CRISTAL): a parallel-group, open-label, randomised controlled trial. Lancet Diabetes Endocrinol. 2024 Jun;12(6):390-403. doi: 10.1016/S2213-8587(24)00089-5. Epub 2024 Apr 30.