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

Primary Purpose

Type1 Diabetes

Status
Completed
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
780G
standard of care
Sponsored by
Universitaire Ziekenhuizen KU Leuven
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Type1 Diabetes focused on measuring closed-loop insulin delivery

Eligibility Criteria

18 Years - 45 Years (Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • OLV Aalst-Asse
  • Imelda Bonheiden
  • AZ St Jan Brugge
  • UCLouvain
  • UZ Brussel
  • UZ Gent
  • AZ Groeninge Kortrijk
  • UZ Leuven
  • AZ Roeselare
  • AZ Nikolaas
  • AZ Turnhout
  • Amsterdam UMC

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

780G closed-loop

standard of care

Arm Description

780 closed-loop insulin delivery system

standard of care treatment (continue with current treatment of insulin pump without closed-loop or multiple daily insulin injections).

Outcomes

Primary Outcome Measures

time in range
time between 63-140mg/dl (pregnancy glycemic target range)

Secondary Outcome Measures

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

Full Information

First Posted
August 12, 2020
Last Updated
September 14, 2023
Sponsor
Universitaire Ziekenhuizen KU Leuven
Collaborators
University Hospital, Ghent, Universitair Ziekenhuis Brussel, University Hospital, Antwerp, Imelda Hospital, Bonheiden, AZ Sint-Jan AV, AZ Delta, Onze Lieve Vrouw Hospital, General Hospital Groeninge, AZ Nikolaas, AZ Turnhout, Cliniques universitaires Saint-Luc- Université Catholique de Louvain, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
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1. Study Identification

Unique Protocol Identification Number
NCT04520971
Brief Title
Closed-loop Insulin Delivery in Pregnant Women With Type 1 Diabetes
Acronym
CRISTAL
Official Title
Closed-loop Insulin Delivery in Pregnant Women With Type 1 Diabetes: a Randomized Controlled Trial: the CRISTAL Study
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Completed
Study Start Date
January 15, 2021 (Actual)
Primary Completion Date
April 30, 2023 (Actual)
Study Completion Date
May 10, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Universitaire Ziekenhuizen KU Leuven
Collaborators
University Hospital, Ghent, Universitair Ziekenhuis Brussel, University Hospital, Antwerp, Imelda Hospital, Bonheiden, AZ Sint-Jan AV, AZ Delta, Onze Lieve Vrouw Hospital, General Hospital Groeninge, AZ Nikolaas, AZ Turnhout, Cliniques universitaires Saint-Luc- Université Catholique de Louvain, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type1 Diabetes
Keywords
closed-loop insulin delivery

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
1/1 randomization to 780G or continue with standard of care
Masking
None (Open Label)
Allocation
Randomized
Enrollment
95 (Actual)

8. Arms, Groups, and Interventions

Arm Title
780G closed-loop
Arm Type
Experimental
Arm Description
780 closed-loop insulin delivery system
Arm Title
standard of care
Arm Type
Active Comparator
Arm Description
standard of care treatment (continue with current treatment of insulin pump without closed-loop or multiple daily insulin injections).
Intervention Type
Device
Intervention Name(s)
780G
Intervention Description
780G closed-loop insulin delivery system (Medtronic)
Intervention Type
Device
Intervention Name(s)
standard of care
Intervention Description
continue with standard of care treatment (pump without closed-loop or MDI)
Primary Outcome Measure Information:
Title
time in range
Description
time between 63-140mg/dl (pregnancy glycemic target range)
Time Frame
from 14 weeks to 36 weeks
Secondary Outcome Measure Information:
Title
time in range during the night
Description
time in range (63-140mg/dl) from midnight till 6am
Time Frame
from 14 weeks to 36 weeks
Title
time below low day and night
Description
time <63mg/dl day and night
Time Frame
from 14 weeks to 36 weeks
Title
overnight time low
Description
time <63mg/dl from midnight till 6am
Time Frame
from 14 weeks to 36 weeks
Title
time in range during the day
Description
time in range (63-140mg/dl) during the day
Time Frame
from 14 weeks to 36 weeks
Title
time in range early pregnancy
Description
time in range (63-140mg/dl) 9-12 weeks
Time Frame
from 9 weeks to 12 weeks
Title
time in range during each trimester
Description
time in range (63-140mg/dl) during each trimester
Time Frame
from 9 weeks to 36 weeks
Title
HbA1c during each trimester
Description
HbA1c (% and mmol/mol) during each trimester
Time Frame
from 9 weeks to 36 weeks
Title
mean glucose
Description
mean glucose based on CGM
Time Frame
from 14 weeks to 36 weeks
Title
time above target (140mg/dl)
Description
time >140mg/dl
Time Frame
from 14 weeks to 36 weeks
Title
time above target (180mg/dl)
Description
time >180mg/dl
Time Frame
from 14 weeks to 36 weeks
Title
time below target (50mg/dl)
Description
time <50mg/dl
Time Frame
from 14 weeks to 36 weeks
Title
time below target (54mg/dl)
Description
time <54mg/dl
Time Frame
from 14 weeks to 36 weeks
Title
duration of hypoglycemia
Description
low blood glucose index
Time Frame
from 14 weeks to 36 weeks
Title
time in nonpregnant target range
Description
time 70-180mg/dl
Time Frame
from 14 weeks to 36 weeks
Title
CGM compliance
Description
% of time use of CGM
Time Frame
from 14 weeks to 36 weeks
Title
insulin dose
Description
total insulin dose
Time Frame
from 14 weeks to 36 weeks
Title
glycemic variability
Description
standard deviation glucose values based on CGM
Time Frame
from 14 weeks to 36 weeks
Title
variation glucose values
Description
coefficient of variation based on CGM
Time Frame
from 14 weeks to 36 weeks
Title
MAGE
Description
mean amplitude of glucose variations based on CGM
Time Frame
from 14 weeks to 36 weeks
Title
nocturnal hypoglycemia
Description
glucose <50mg/dl from 23-07hour
Time Frame
from 9 weeks to 36 weeks
Title
severe hypoglycemia
Description
hypoglycemia requiring third-part assistance
Time Frame
from 9 weeks to 36 weeks
Title
rate of diabetic keto-acidosis
Description
metabolic keto-acidosis with decreased ph and/or decreased bicarbonate in blood
Time Frame
from 9 weeks to 36 weeks
Title
gestational duration
Description
duration of pregnancy (weeks)
Time Frame
delivery
Title
duration hospitalization delivery
Description
length of hospital stay (days)
Time Frame
delivery
Title
type of labor
Description
spontaneous, induced or cesarean section before labor
Time Frame
delivery
Title
type of delivery
Description
vaginal, forceps or vacuum, cesarean section during labor or planned cesarean section
Time Frame
delivery
Title
rate of preterm delivery
Description
delivery <37 weeks
Time Frame
delivery
Title
rate of gestational hypertension
Description
blood pressure of 140/90mmHg or higher starting after 20 weeks of gestation
Time Frame
from 20 weeks to delivery
Title
rate of worsening of chronic hypertension
Description
blood pressure of 140/90mmHg or higher start is present before 20 weeks of gestation
Time Frame
from 9 weeks to delivery
Title
rate of preeclampsia
Description
onset of new hypertension and proteinuria and/or end-organ dysfunction after 20 weeks of gestation
Time Frame
from 20 weeks to delivery
Title
rate of eclampsia
Description
generalized convulsions and/or coma
Time Frame
from 20 weeks to delivery
Title
rate of HELLP syndrome
Description
hemolysis, elevated liver enzymes and a low platelet count
Time Frame
from 20 weeks to delivery
Title
rate of IUGR
Description
intra-uterine growth restriction
Time Frame
from 20 weeks to delivery
Title
rate of fetal malformation
Description
congenital malformation
Time Frame
up to 24 weeks
Title
rate of miscarriage
Description
fetal loss <20 weeks gestations
Time Frame
<20 weeks
Title
rate of termination of pregnancy
Description
induced abortion
Time Frame
up to 24 weeks
Title
rate of stillbirth
Description
mors in utero >20 weeks
Time Frame
>20 weeks
Title
rate of neonatal death
Description
death <1 months after delivery
Time Frame
1 month after delivery
Title
sex of infant
Description
boy or girl
Time Frame
delivery
Title
birth weight
Description
birth weight (Kg and g)
Time Frame
delivery
Title
rate of shoulder dystocia
Description
one or both of a baby's shoulders get stuck inside the mother's pelvis during labor.
Time Frame
delivery
Title
rate of birth trauma
Description
fracture, damage to nerves...
Time Frame
delivery
Title
rate of respiratory distress
Description
respiratory failure or distress
Time Frame
delivery
Title
rate of hyperbilirubinaemia
Description
hyperbilirubinaemia with need of treatment with phototherapy
Time Frame
delivery
Title
rate of macrosomia
Description
birth weight >4Kg
Time Frame
delivery
Title
rate with high birth weight
Description
birth weight >4.5Kg
Time Frame
delivery
Title
rate of LGA infant (lage for gestational age)
Description
gestational age adjusted birth weight >90th percentile according to the standardized Flemish birth charts adjusted for parity and sex
Time Frame
delivery
Title
rate of SGA infant (small for gestational age)
Description
gestational age adjusted birth weight <10th percentile according to the standardized Flemish birth charts adjusted for parity and sex
Time Frame
delivery
Title
number with very large gestational age infants
Description
gestational age adjusted birth weight >97th percentile according to the standardized Flemish birth charts adjusted for parity and sex
Time Frame
delivery
Title
cord blood ph
Description
cord blood gas ph
Time Frame
delivery
Title
rate of neonatal hypoglycemia
Description
neonatal hypoglycemia requiring intravenous dextrose
Time Frame
up to 5 days after delivery
Title
rate of NICU admission
Description
Neonatal intensive care unit (NICU) admission defined as requiring a duration of at least 24 h
Time Frame
up to 30 days after delivery
Title
duration NICU admission
Description
duration of NICU admission (days or weeks)
Time Frame
up to 30 days after delivery
Title
rate of fetal hyperinsulinemia
Description
cord blood c-peptide
Time Frame
delivery
Title
skinfolds newborn
Description
sum of skinfolds (triceps, scapula and flank)
Time Frame
up to 3 days after delivery
Title
neonatal fat mass
Description
fat mass calculated by the formula of Catalano
Time Frame
up to 3 days after delivery
Title
number with composite neonatal outcome
Description
pregnancy loss (miscarriage, still birth or neonatal death), LGA, respiratory distress syndrome, birth trauma, shoulder dystocia, neonatal hypoglycemia and NICU admission
Time Frame
delivery

10. Eligibility

Sex
Female
Gender Based
Yes
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Katrien Benhalima, MD PhD
Organizational Affiliation
UZ Leuven
Official's Role
Principal Investigator
Facility Information:
Facility Name
OLV Aalst-Asse
City
Aalst
State/Province
Oost-Vlaanderen
ZIP/Postal Code
9300
Country
Belgium
Facility Name
Imelda Bonheiden
City
Bonheiden
ZIP/Postal Code
2820
Country
Belgium
Facility Name
AZ St Jan Brugge
City
Brugge
ZIP/Postal Code
8000
Country
Belgium
Facility Name
UCLouvain
City
Brussels
Country
Belgium
Facility Name
UZ Brussel
City
Brussel
ZIP/Postal Code
1090
Country
Belgium
Facility Name
UZ Gent
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
AZ Groeninge Kortrijk
City
Kortrijk
ZIP/Postal Code
8510
Country
Belgium
Facility Name
UZ Leuven
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
AZ Roeselare
City
Roeselare
ZIP/Postal Code
8800
Country
Belgium
Facility Name
AZ Nikolaas
City
Sint-Niklaas
ZIP/Postal Code
9100
Country
Belgium
Facility Name
AZ Turnhout
City
Turnhout
Country
Belgium
Facility Name
Amsterdam UMC
City
Amsterdam
Country
Netherlands

12. IPD Sharing Statement

Learn more about this trial

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

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