Continuous Glucose Monitoring in Women With Type 1 Diabetes in Pregnancy Trial (CONCEPTT)

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.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetics Who Are Pregnant or Planning Pregnancy
• Intervention / Treatment: Device: CGM

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.

• Study Type: Interventional
• Enrollment (Actual): 325
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2T 5C7
      • Alberta Health Services - Calgary Zone
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3K 6R8
      • IWK Health Centre
  • Ontario
    • Hamilton, Ontario, Canada, L9H 1V1
      • McMaster University
    • Kingston, Ontario, Canada, K7L 2V7
      • Kingston General Hospital
    • London, Ontario, Canada, N6A 4V2
      • St Joseph's Health Care
    • Ottawa, Ontario, Canada, K1H 7W9
      • The Ottawa Hospital
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre
    • Toronto, Ontario, Canada, M5G 1X5
      • Mount Sinai Hospital
  • Quebec
    • Montreal, Quebec, Canada, H2X 3J4
      • St-Luc Hospital- Centre hospitalier de L'Universite de Montreal
    • Quebec City, Quebec, Canada, G1V 4G2
      • Chuq-Chul
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 0W8
      • Royal University Saskatoon
• Ireland
  • Galway, Ireland
    • Galway University Hospital
• Italy
  • Milan, Italy, 20162
    • Niguarda Ca' Granda Hospital
• Spain
  • Barcelona, Spain, 08025
    • Hospital de la Santa Creu i Sant Pau
• United Kingdom
  • Cambridge, United Kingdom
    • Addenbrooke's Hospital
  • Ipswich, United Kingdom, IP4 5PD
    • Ipswich Hospital NHS Trust
  • Leeds, United Kingdom, LS9 7TF
    • St James University Hospital
  • London, United Kingdom
    • Kings College Hospital
  • London, United Kingdom
    • Guys & St. Thomas'
  • Manchester, United Kingdom, M139WL
    • Manchester University Hospital NHS Trust
  • Middlesbrough, United Kingdom, TS4 3BW
    • South Tees Hospital NHS Trust
  • Newcastle, United Kingdom, NE1 4EP
    • Royal Victoria Infirmary
  • Norwich, United Kingdom, NR4 7UY
    • Norfolk and Norwich University Hospital
  • Nottingham, United Kingdom, NG72UH
    • Queen's Medical Centre
  • Sheffield, United Kingdom, S10 2RX
    • Sheffield Teaching Hospitals
  • Southampton, United Kingdom, SO16 6YD
    • Princess Anne Hospital
  • Scotland
    • Aberdeen, Scotland, United Kingdom, AB25 2ZP
      • University of Aberdeen
    • Edinburgh, Scotland, United Kingdom, EH16 4TJ
      • Royal Infirmary of Edinburgh
    • Glasgow, Scotland, United Kingdom, G31 2ER
      • Glasgow Royal Infirmary
  • West Midlands
    • Dudley, West Midlands, United Kingdom, DY1 2HQ
      • Russells Hall Hospital
• United States
  • California
    • Santa Barbara, California, United States, 93105
      • Sansum Diabetes Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CGM; Continuous Glucose Monitoring	Device: CGM; Real Time Continuous Glucose Monitoring
No Intervention: HGM; Standard of care, Home Glucose Monitoring

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glycemic Control in pre-pregnant group	Glycemic control as measured by HbA1c at 24 weeks or at conception. If the patient becomes pregnant, than a HbA1c will be measured post-confirmation of a positive pregnancy test and will contribute to the primary outcome.	24 weeks or at conception
Glycemic Control in pregnant group	Glycemic control as measured by HbA1c at 34 weeks gestation. In women who do not progress to 34 weeks gestation, the latest measured HbA1c will be used to contribute to the primary outcome.	34 weeks gestation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time in target in pre-pregnant group	Time in target at 12 and 24 weeks after randomization	12 and 24 weeks after randomization
HbA1c and time in target, in pre-pregnant group who became pregnant within 24 weeks from randomization	HbA1c and Time in target at post-confirmation of a positive pregnancy test, 24 weeks and 34 weeks gestation for those who start pre-pregnant and become pregnant	24 weeks and 34 weeks gestation
Time in target in pregnant group	Time in target at randomization, 24 weeks and 34 weeks gestation	Randomization, 24 weeks and 34 weeks gestation
HbA1c measurement in pregnant group	HbA1c at randomization, 24 weeks and 34 weeks gestation	24 weeks and 34 weeks gestation
Hypertension in pregnant group	Incidence of worsening chronic hypertension, gestational hypertension, preeclampsia; total and individual measures	Up to 42 weeks gestation
Caesarean sections in pregnant group	Caesarean section: primary and total	At delivery
Gestational weight gain in pregnant group	Entry to 34 weeks gestation; 16 weeks to 34 weeks gestation	Up to 34 weeks gestation
AUC	Area under the curve for blood sugars (a) >7.8 mmol/l or 140 mg/dl (b)>6.7 mmol/l or 120 mg/dl (c) <3.5 mmol/L or <63 mg/dl (d) <2.8 mmol/L or <50 mg/dl	At delivery
Incidence of Clinical events	Episodes of 'severe hypoglycemia' requiring assistance; mild-moderate episodes of hypoglycemia <3.5 (mild) and <2.8 (moderate) from CGM data defined as AUC <3.5 or AUC less than or equal to 2.8 for 20 minutes duration; nocturnal hypoglycemia (NH) defined as CGM glucose <3.5 (mild) and <2.8 (moderate) between the hours of 23.00-07.00	Up to 42 weeks gestation
Glucose variability	Mean amplitude of glycemic excursions (MAGE); Coefficient of Variation (CV); Standard deviation (SD) of CGM measurements; mean absolute rate of change of CGM based on one week of sensor values	Up to delivery
Hospital stay	Length of hospital stay	Admission until hospital discharge
Infant Outcomes	Infant birthweight >90th centile using customized growth curves; infant birthweight <10th centile using customized growth curves; infant birthweight >=4kg	At birth of infant
Infant Outcomes	Pregnancy loss (Miscarriage, stillbirth, neonatal death)	=<28 days of life
Infant Outcomes	Preterm delivery (<37 weeks and early preterm <34 weeks)	At birth
Infant Outcomes	Birth injury	Until hospital discharge
Infant outcomes	Shoulder dystocia	Until hospital discharge
Infant outcomes	Neonatal hypoglycemia with intravenous dextrose	Until hospital discharge
Infant Outcomes	Hyperbilirubinemia	Within first 7 days of life
Infant Outcomes	Respiratory Distress Syndrome (RDS)	Within first 7 days of life
Infant Outcomes	NICU admission > 24 hrs	Until hospital discharge
Infant Outcomes	Cord blood gas pH <7.0	At birth
Infant Outcomes	Hyperinsulinemia (using Cord C-peptide)	At birth
Infant Outcomes	Composite fetal outcome: pregnancy loss:miscarriage, stillbirth, neonatal death (death<=28 days of life), birth injury, neonatal hypoglycemia, hyperbilirubinemia, respiratory distress syndrome requiring therapy, NICU admission >24 hours	Within first 7 days of life or until hospital discharge (whichever is last)
Infant Outcomes	Sum of skinfolds >90th percentile for gestational age	Within first 3 days of life
Infant Outcomes	Other anthropometric measures	Within first 3 days of life
Infant Outcomes	Length of hospital stay	Until hospital discharge
Insulin requirements	Units per kg per day	Pre-pregnant (randomization, 12 weeks, 24 weeks); Pregnant (randomization, 24 weeks and 34 weeks gestation)
Questionnaires	BGMSRQ, HFS, PAID, SF12, CGM-SAT; NWTSQ	Baseline and 24 weeks or at confirmed pregnancy (pre-pregnant); Baseline and 34 weeks (pregnant)
Study Contacts	Scheduled and unscheduled visits	Up to delivery

Collaborators and Investigators

• Sponsor: Mount Sinai Hospital, Canada
• Collaborators: Cambridge University Hospitals NHS Foundation Trust; University of Cambridge; Jaeb Center for Health Research; Sunnybrook Research Institute
• Investigators: Principal Investigator: Denice Feig, MD, Mount Sinai Hospital; Principal Investigator: Helen Murphy, MB BCh BAO FRACP MD, Cambridge University Hospital NHS Foundation Trust and University of Cambridge

Publications and helpful links

General Publications

• 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.
• 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.
• Meek CL, Corcoy R, Asztalos E, Kusinski LC, López 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.
• 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.
• 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.
• 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. Erratum In: Lancet. 2017 Nov 25;390(10110):2346.
• 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. Erratum In: BMC Pregnancy Childbirth. 2016;16:249.

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: December 19, 2012
• First Submitted That Met QC Criteria: February 7, 2013
• First Posted (Estimate): February 11, 2013

Study Record Updates

• Last Update Posted (Actual): July 19, 2017
• Last Update Submitted That Met QC Criteria: July 14, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: Diabetes; HbA1c; CGM; Continuous Glucose Monitor; Type 1; HGM
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Pregnancy Complications; Diabetes, Gestational; Pregnancy in Diabetics
• Other Study ID Numbers: 12-0037-A