Clinical trial NCT01788527: Continuous Glucose Monitoring in Women With Type 1 Diabetes in Pregnancy Trial
Official title: Continuous Glucose Monitoring in Women With Type 1 Diabetes in Pregnancy Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type 1 Diabetics Who Are Pregnant or Planning Pregnancy
Keywords: Diabetes
Type 1
CGM
Continuous Glucose Monitor
HGM
HbA1c
Lead sponsor: Mount Sinai Hospital, Canada
Sponsor class: OTHER
Collaborators: name: Sunnybrook Research Institute
name: Jaeb Center for Health Research
name: Cambridge University Hospitals NHS Foundation Trust
name: University of Cambridge
First posted: 2013-02-11
Enrollment: 325
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of the study is to determine if RT CGM (Real Time-Continuous Glucose Monitoring) can improve glycemic control in women with T1D who are pregnant or planning pregnancy.

Detailed description: In women with diabetes, hyperglycemia is associated with increased rates of numerous maternal and fetal adverse outcomes. Mothers are at increased risk of preeclampsia, polyhydramnios, and caesarean sections. Infants of mothers with diabetes have increased rates of congenital anomalies, premature delivery, macrosomia, stillbirth and NICU admissions. Macrosomia itself is associated with numerous adverse fetal outcomes including shoulder dystocia, birth injury, neonatal hypoglycemia, hyperbilirubinemia, respiratory distress syndrome and NICU admissions, asphyxia and death. Postprandial blood sugars in particular have been associated with increased macrosomia rates.

Numerous studies have shown that pregnancy outcomes can be reduced with improved glycemic control. In particular, pre-pregnancy care has been shown to assist women improve glucose control during the crucial period of organogenesis, and is associated with reduced rates of adverse pregnancy outcome including major congenital malformation, stillbirth and neonatal death.

Technological advances aimed at reducing glycemic excursions and improving glucose control in patients with diabetes include the continuous glucose monitoring (CGM) system. We hypothesize that real-time CGM will assist women with type 1 diabetes to improve their glycemic control before and during pregnancy.

Eligibility criteria: Inclusion Criteria:

* Clinical diagnosis of type 1 diabetes and using daily insulin therapy for at least one year
* Age 18-40 years
* Insulin regimen involves either the use of an insulin pump or multiple daily injections of insulin (at least 3 shots per day). Subjects using premixed fixed doses of insulin at the time of enrolment will not be eligible. Insulin regimen must be stable for at least 4 weeks (i.e. on multiple insulin injections or on insulin pump) prior to randomization.
* No expectation that subject will be moving out of the area of the clinical center during the next year, unless the move will be to an area served by another study center
* Informed Consent Form signed by the subject

In addition, specific eligibility criteria apply to the respective groups:

Pre-pregnancy Group:

* Patients who are planning pregnancy and wish to optimise glycemic control before conception

Pregnancy Group:

* Pregnancy gestation ≤13 weeks, 6 days at time of randomization
* Live singleton fetus
* Dating ultrasound (US) done to confirm gestational age, viability and rule out multiples. Gestational age will be based on the last menstrual period (LMP) provided there is a ≤5 day discrepancy with US dates in the first trimester and ≤10 day discrepancy with US dates in the second trimester. If the dates from LMP are outside these limits, the US dates will be used as the best estimate of gestational age.

Exclusion Criteria:

* Type 2 diabetes
* Gestational diabetes
* Previous participation in the study
* Estimated GFR \<60 ml/min/1.73
* The presence of a significant medical disorder or use of a medication such as oral glucocorticoids that in the judgment of the investigator will affect the wearing of the sensors or the completion of any aspect of the protocol.

If the investigator is uncertain whether the patient would be eligible; i.e. if the medical disorder would constitute an exclusion, the Steering Committee will be asked to make the decision.

* Inpatient psychiatric treatment in the past 6 months
* Subjects using premixed fixed doses of insulin at the time of enrolment

In addition, specific exclusion criteria apply to the respective groups:

Pre-pregnancy Group:

* HbA1c \<7.0% or \>10.0%

Pregnancy Group:

* HbA1c \<6.5% or \>10.0%
* Known current higher order pregnancies (twins, triplets, etc.) These women will be excluded as they have a higher rate of adverse outcomes and could lead to inequalities if they are unequally distributed between the groups.
* Known potentially major fetal anomaly (as per EUROCAT criteria).

Primary outcomes:
measure: Glycemic Control in pre-pregnant group
timeFrame: 24 weeks or at conception
measure: Glycemic Control in pregnant group
timeFrame: 34 weeks gestation
Secondary outcomes:
measure: Time in target in pre-pregnant group
timeFrame: 12 and 24 weeks after randomization
measure: HbA1c and time in target, in pre-pregnant group who became pregnant within 24 weeks from randomization
timeFrame: 24 weeks and 34 weeks gestation
measure: Time in target in pregnant group
timeFrame: Randomization, 24 weeks and 34 weeks gestation
measure: HbA1c measurement in pregnant group
timeFrame: 24 weeks and 34 weeks gestation
measure: Hypertension in pregnant group
timeFrame: Up to 42 weeks gestation
measure: Caesarean sections in pregnant group
timeFrame: At delivery
measure: Gestational weight gain in pregnant group
timeFrame: Up to 34 weeks gestation
measure: AUC
timeFrame: At delivery
measure: Incidence of Clinical events
timeFrame: Up to 42 weeks gestation
measure: Glucose variability
timeFrame: Up to delivery
measure: Hospital stay
timeFrame: Admission until hospital discharge
measure: Infant Outcomes
timeFrame: At birth of infant
measure: Infant Outcomes
timeFrame: =<28 days of life
measure: Infant Outcomes
timeFrame: At birth
measure: Infant Outcomes
timeFrame: Until hospital discharge
measure: Infant outcomes
timeFrame: Until hospital discharge
measure: Infant outcomes
timeFrame: Until hospital discharge
measure: Infant Outcomes
timeFrame: Within first 7 days of life
measure: Infant Outcomes
timeFrame: Within first 7 days of life
measure: Infant Outcomes
timeFrame: Until hospital discharge
measure: Infant Outcomes
timeFrame: At birth
measure: Infant Outcomes
timeFrame: At birth
measure: Infant Outcomes
timeFrame: Within first 7 days of life or until hospital discharge (whichever is last)
measure: Infant Outcomes
timeFrame: Within first 3 days of life
measure: Infant Outcomes
timeFrame: Within first 3 days of life
measure: Infant Outcomes
timeFrame: Until hospital discharge
measure: Insulin requirements
timeFrame: Pre-pregnant (randomization, 12 weeks, 24 weeks); Pregnant (randomization, 24 weeks and 34 weeks gestation)
measure: Questionnaires
timeFrame: Baseline and 24 weeks or at confirmed pregnancy (pre-pregnant); Baseline and 34 weeks (pregnant)
measure: Study Contacts
timeFrame: Up to delivery
Other outcomes:
Locations:
city: Santa Barbara
country: United States
facility: Sansum Diabetes Research Institute
state: California
city: Calgary
country: Canada
facility: Alberta Health Services - Calgary Zone
state: Alberta
city: Halifax
country: Canada
facility: IWK Health Centre
state: Nova Scotia
city: Hamilton
country: Canada
facility: McMaster University
state: Ontario
city: Kingston
country: Canada
facility: Kingston General Hospital
state: Ontario
city: London
country: Canada
facility: St Joseph's Health Care
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
city: Montreal
country: Canada
facility: St-Luc Hospital- Centre hospitalier de L'Universite de Montreal
state: Quebec
city: Quebec City
country: Canada
facility: Chuq-Chul
state: Quebec
city: Saskatoon
country: Canada
facility: Royal University Saskatoon
state: Saskatchewan
city: Galway
country: Ireland
facility: Galway University Hospital
city: Milan
country: Italy
facility: Niguarda Ca' Granda Hospital
city: Barcelona
country: Spain
facility: Hospital De La Santa Creu I Sant Pau
city: Aberdeen
country: United Kingdom
facility: University of Aberdeen
state: Scotland
city: Edinburgh
country: United Kingdom
facility: Royal Infirmary of Edinburgh
state: Scotland
city: Glasgow
country: United Kingdom
facility: Glasgow Royal Infirmary
state: Scotland
city: Dudley
country: United Kingdom
facility: Russells Hall Hospital
state: West Midlands
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
city: Ipswich
country: United Kingdom
facility: Ipswich Hospital NHS Trust
city: Leeds
country: United Kingdom
facility: St James University Hospital
city: London
country: United Kingdom
facility: Guys & St. Thomas'
city: London
country: United Kingdom
facility: Kings College Hospital
city: Manchester
country: United Kingdom
facility: Manchester University Hospital NHS Trust
city: Middlesbrough
country: United Kingdom
facility: South Tees Hospital NHS Trust
city: Newcastle
country: United Kingdom
facility: Royal Victoria Infirmary
city: Norwich
country: United Kingdom
facility: Norfolk and Norwich University Hospital
city: Nottingham
country: United Kingdom
facility: Queen's Medical Centre
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospitals
city: Southampton
country: United Kingdom
facility: Princess Anne Hospital
Study officials:
affiliation: MOUNT SINAI HOSPITAL
name: Denice Feig, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Cambridge University Hospital NHS Foundation Trust and University of Cambridge
name: Helen Murphy, MB BCh BAO FRACP MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ahmed RJ, Gafni A, Hutton EK, Hu ZJ, Sanchez JJ, Murphy HR, Feig DS; CONCEPTT Collaborative Group. The cost implications of continuous glucose monitoring in pregnant women with type 1 diabetes in 3 Canadian provinces: a posthoc cost analysis of the CONCEPTT trial. CMAJ Open. 2021 Jun 4;9(2):E627-E634. doi: 10.9778/cmajo.20200128. Print 2021 Apr-Jun.
citation: Tundidor D, Meek CL, Yamamoto J, Martinez-Bru C, Gich I, Feig DS, Murphy HR, Corcoy R; CONCEPTT Collaborative Group. Continuous Glucose Monitoring Time-in-Range and HbA1c Targets in Pregnant Women with Type 1 Diabetes. Diabetes Technol Ther. 2021 Oct;23(10):710-714. doi: 10.1089/dia.2021.0073. Epub 2021 May 25.
citation: Meek CL, Corcoy R, Asztalos E, Kusinski LC, Lopez E, Feig DS, Murphy HR; CONCEPTT collaborative group. Which growth standards should be used to identify large- and small-for-gestational age infants of mothers with type 1 diabetes? A pre-specified analysis of the CONCEPTT trial. BMC Pregnancy Childbirth. 2021 Jan 29;21(1):96. doi: 10.1186/s12884-021-03554-6.
citation: Meek CL, Tundidor D, Feig DS, Yamamoto JM, Scott EM, Ma DD, Halperin JA, Murphy HR, Corcoy R; CONCEPTT Collaborative Group. Novel Biochemical Markers of Glycemia to Predict Pregnancy Outcomes in Women With Type 1 Diabetes. Diabetes Care. 2021 Mar;44(3):681-689. doi: 10.2337/dc20-2360. Epub 2021 Jan 25.
citation: Neoh SL, Yamamoto JM, Feig DS, Murphy HR; CONCEPTT Collaborative Group. Dietary Patterns of Insulin Pump and Multiple Daily Injection Users During Type 1 Diabetes Pregnancy. Diabetes Care. 2020 Jan;43(1):e5-e7. doi: 10.2337/dc19-1908. Epub 2019 Nov 6. No abstract available.
citation: Feig DS, Donovan LE, Corcoy R, Murphy KE, Amiel SA, Hunt KF, Asztalos E, Barrett JFR, Sanchez JJ, de Leiva A, Hod M, Jovanovic L, Keely E, McManus R, Hutton EK, Meek CL, Stewart ZA, Wysocki T, O'Brien R, Ruedy K, Kollman C, Tomlinson G, Murphy HR; CONCEPTT Collaborative Group. Continuous glucose monitoring in pregnant women with type 1 diabetes (CONCEPTT): a multicentre international randomised controlled trial. Lancet. 2017 Nov 25;390(10110):2347-2359. doi: 10.1016/S0140-6736(17)32400-5. Epub 2017 Sep 15.
citation: Feig DS, Asztalos E, Corcoy R, De Leiva A, Donovan L, Hod M, Jovanovic L, Keely E, Kollman C, McManus R, Murphy K, Ruedy K, Sanchez JJ, Tomlinson G, Murphy HR; CONCEPTT Collaborative Group. CONCEPTT: Continuous Glucose Monitoring in Women with Type 1 Diabetes in Pregnancy Trial: A multi-center, multi-national, randomized controlled trial - Study protocol. BMC Pregnancy Childbirth. 2016 Jul 18;16(1):167. doi: 10.1186/s12884-016-0961-5.