Clinical trial NCT06490874: Continuous Glucose Monitoring (CGM) Substudy of the DECIDE RCT
Official title: Continuous Glucose Monitoring Among Individuals With Gestational Diabetes Treated With Metformin Versus Insulin: Protocol for a Nested Prospective Cohort in the DECIDE RCT (DECIDE CGM)
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Gestational Diabetes Mellitus
Pregnancy, High Risk
Keywords: Insulin
Pregnancy
Glycemic control
Metformin
Gestational diabetes
Diabetes
Adverse pregnancy outcomes
Continuous glucose monitoring
Lead sponsor: Ohio State University
Sponsor class: OTHER
Collaborators: name: The George Washington University Biostatistics Center
name: DexCom, Inc.
First posted: 2024-07-08
Enrollment: 300
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: A subset of 300 individuals (150 metformin, 150 insulin) will be consecutively enrolled in participating sites to this substudy from the 1,572 individuals from the parent DECIDE trial (NCT06445946).

Brief summary: This is a nested multicenter prospective cohort conducted concurrently and in conjunction with the DECIDE two-arm, pragmatic non-inferiority comparative effectiveness Randomized Controlled Trial (RCT) (NCT06445946) of metformin versus insulin among individuals with Gestational diabetes mellitus (GDM) requiring pharmacotherapy for glycemic control. Continuous Glucose Monitoring (CGM)-derived glycemic metric in pregnancy and postpartum will be compared between individuals randomized to metformin versus insulin. In addition, the association between CGM metrics and adverse pregnancy outcomes will be examined. Finally, whether CGM metrics can accurately identify diabetes postpartum compared with an oral glucose tolerance test and hemoglobin A1c will be determined. A total of 300 (150 metformin, 150 insulin) pregnant individuals will be recruited with GDM who require pharmacotherapy to use a blinded CGM device (Dexcom, Inc, San Diego, CA) at two pregnancy (medication randomization, late third trimester) and three postpartum timepoints (delivery, \~6 weeks, and \~2 years).

Detailed description: Gestational diabetes mellitus (GDM) is the most frequent metabolic complication of pregnancy, and affects nearly 1 in 10 pregnant individuals in the U.S. annually. GDM increases the risks of both adverse pregnancy and postpartum outcomes for the affected individual and exposed offspring. Following a diagnosis of GDM, individuals are instructed to achieve glycemic control to decrease the risk of adverse pregnancy outcomes through monitoring of blood glucose, dietary modifications, and increased physical activity. However, \>1 in 4 individuals with GDM will not achieve targeted glycemic control with diet and behavior changes alone, and require pharmacotherapy.

This is a multicenter prospective observational cohort nested in the DECIDE randomized controlled trial (NCT06445946). DECIDE is a two-arm, pragmatic non-inferiority comparative effectiveness RCT of metformin versus insulin to prevent adverse pregnancy outcomes and to confirm postpartum safety among individuals with GDM who require pharmacotherapy to achieve glycemic control. This trial will determine whether metformin is not inferior to insulin in reducing adverse pregnancy outcomes and is comparably safe for exposed pregnant individuals and their children. This substudy will be conducted concurrently and in conjunction with the parent study. A subset of 300 individuals (150 metformin, 150 insulin) will be enrolled in this substudy from the 1,572 individuals from the parent trial.

Primary aim:

To compare CGM-derived glycemic profiles (primary outcome: time in range of 63 to 140 mg/dL; secondary outcomes (mean glucose, coefficient of variation, and percentage of time below the target glucose range or above the target glucose range) in pregnancy between individuals with GDM randomized to metformin versus insulin.

Secondary aims:

To examine the association between CGM metrics and adverse pregnancy outcomes (large-for-gestational-age at birth, neonatal hypoglycemia, and hyperbilirubinemia, hypertensive disorder of pregnancy, preterm birth \<37 weeks, NICU admission, neonatal mechanical ventilation, neonatal oxygen support, neonatal respiratory distress syndrome).

To examine whether CGM metrics can identify diabetes and postpartum cardiometabolic outcomes (prediabetes, type 2 diabetes, impaired glucose tolerance, impaired fasting glucose, hypertension, obesity, and cholesterol abnormalities) compared with an oral glucose tolerance test or hemoglobin A1c.

Eligibility criteria: Inclusion Criteria:

* Singleton gestation. Twin reduction to singleton, either spontaneously or therapeutically, is eligible if it occurred before 14 weeks gestational age.
* Age \>18 years
* Gestational age at randomization between 200/7 - 316/7 weeks based on project gestational age.
* GDM diagnosis between 200/7 - 316/7 weeks based on project gestational age.
* Requires medication for glucose control defined as ≥30% elevated glucose values (either fasting or postprandial or both) in the week prior to randomization per determination of the provider or documented in the medical record.
* Patient willingness and ability to attend 2-year follow-up visit.
* Patient willingness to wear and return a blinded CGM device. It is possible that some enrolled individuals may choose to use a separate CGM device for glucose monitoring as part of clinical care.

Exclusion Criteria:

* Renal disease (serum creatinine \>1.3 mg/dL) due to the potential impact of metformin on renal function.
* Major structural malformation of the fetus.
* Known fetal aneuploidy based on invasive testing or positive for aneuploidy on cell-free fetal DNA screening.
* Contraindication to metformin or insulin, including: history of lactic acidosis, intractable nausea and vomiting, prior documented allergy and/or anaphylaxis.
* Pregestational diabetes documented in the medical record, GDM diagnosis \<20 weeks, or prior A1c\>6.5%
* Fasting hyperglycemia \>115 mg/dl for ≥50% of fasting glucose values in the past week (due to the high risk of metformin failure with fasting hyperglycemia).
* Enrolled in a trial that influences primary study outcomes of the parent DECIDE trial (composite neonatal outcome at delivery or childhood body mass index at 2 years).
* Prenatal care or delivery planned at a location where access to the complete electronic medical record will not be available to research staff.
* Language barrier (appropriate translation resources unavailable at the site).
* Participation in this trial in a previous pregnancy. Patients who were screened in a previous pregnancy, but not randomized, may be included.
* In addition, individuals who report a prior allergy or sensitivity to CGM will also be excluded.

Primary outcomes:
measure: Time in range (TIR)
timeFrame: From medication randomization till late third trimester, up to 14 weeks
Secondary outcomes:
measure: Coefficient of variation (CV)
timeFrame: From medication randomization till 2 years postpartum, up to 40 months.
measure: Time below range (TBR)
timeFrame: From medication randomization till 2 years postpartum, up to 40 months.
measure: Time above range (TAR)
timeFrame: From medication randomization till 2 years postpartum, up to 40 months.
measure: Large-for-gestational-age at birth
timeFrame: At delivery
measure: Hypoglycemia
timeFrame: <24 hours after birth
measure: Hyperbilirubinemia
timeFrame: Within one week after birth
measure: Hypertensive disorder of pregnancy
timeFrame: Randomization to delivery
measure: Preterm birth
timeFrame: At birth
measure: Requiring mechanical ventilation
timeFrame: <72 hours after birth
measure: NICU admission
timeFrame: Birth to infant date of delivery discharge (length of NICU admission will vary for each infant )
measure: Oxygen support
timeFrame: <72 hours after birth
measure: Respiratory distress syndrome
timeFrame: Anytime during the first 72 hours after birth
measure: Treatment supplementation
timeFrame: From randomization to delivery
measure: Type 2 diabetes (T2D)
timeFrame: From delivery to 2 years postpartum
measure: Prediabetes
timeFrame: From delivery to 2 years postpartum
measure: Impaired glucose tolerance (IGT)
timeFrame: From delivery to 2 years postpartum
measure: Impaired fasting glucose (IFG)
timeFrame: From delivery to 2 years postpartum.
measure: Obesity overall and by class
timeFrame: 2 years postpartum
measure: Hypertension
timeFrame: 2 years postpartum
measure: Cholesterol
timeFrame: 2 years postpartum
measure: Mean glucose
timeFrame: From medication randomization till 2 years postpartum, up to 40 months.
Other outcomes:
Locations:
city: Tuscaloosa
country: United States
facility: University of Alabama
state: Alabama
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center OB/GYN Maternal and Fetal Medicine
state: Ohio
city: Dayton
country: United States
facility: Premier Health - Miami Valley Hospital
state: Ohio
Study officials:
affiliation: Ohio State University
name: Kartik Venkatesh, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ohio State University
name: Donna Gregory, RNC, BSN
role: STUDY_DIRECTOR
References: