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

Type1 Diabetes Clinical Trial

— CRISTAL  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04520971
• Other study ID #: S64308
• Status: Completed
• Phase: N/A
• Start date: January 15, 2021
• Est. completion date: May 10, 2023

Study information

• Verified date: September 2023
• Source: Universitaire Ziekenhuizen KU Leuven
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 95
• Est. completion date: May 10, 2023
• Est. primary completion date: April 30, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type1 Diabetes

Intervention

Device:
• 780G
780G closed-loop insulin delivery system (Medtronic)
• standard of care
continue with standard of care treatment (pump without closed-loop or MDI)

Locations

Country	Name	City	State
Belgium	OLV Aalst-Asse	Aalst	Oost-Vlaanderen
Belgium	Imelda Bonheiden	Bonheiden
Belgium	AZ St Jan Brugge	Brugge
Belgium	UZ Brussel	Brussel
Belgium	UCLouvain	Brussels
Belgium	UZ Gent	Gent
Belgium	AZ Groeninge Kortrijk	Kortrijk
Belgium	UZ Leuven	Leuven
Belgium	AZ Roeselare	Roeselare
Belgium	AZ Nikolaas	Sint-Niklaas
Belgium	AZ Turnhout	Turnhout
Netherlands	Amsterdam UMC	Amsterdam

Sponsors (13)

Lead Sponsor	Collaborator
Universitaire Ziekenhuizen KU Leuven	Amsterdam UMC, AZ Delta, AZ Nikolaas, AZ Sint-Jan AV, AZ Turnhout, Cliniques universitaires Saint-Luc- Université Catholique de Louvain, General Hospital Groeninge, Imelda Hospital, Bonheiden, Onze Lieve Vrouw Hospital, Universitair Ziekenhuis Brussel, University Hospital, Antwerp, University Hospital, Ghent

Countries where clinical trial is conducted

Belgium,  Netherlands, 

References & Publications (2)

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 insuli — View 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. — View Citation

Outcome

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