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)
试验速览
- 阶段
- 不适用
- 状态
- 撤回
- 入组人数
- 300
- 试验地点
- 4
- 主要终点
- Time in range (TIR)
研究概览
简要总结
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).
详细描述
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:
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
结局指标
主要结局
Time in range (TIR)
时间窗: From medication randomization till late third trimester, up to 14 weeks
Percent of time CGM readings are within the pregnancy target glucose range of 63 to 140 mg/dL. This outcome will be assessed as a continuous measure in increments of 1%.
次要结局
- Preterm birth(At birth)
- Oxygen support(<72 hours after birth)
- Hyperbilirubinemia(Within one week after birth)
- NICU admission(Birth to infant date of delivery discharge (length of NICU admission will vary for each infant ))
- Time below range (TBR)(From medication randomization till 2 years postpartum, up to 40 months.)
- Coefficient of variation (CV)(From medication randomization till 2 years postpartum, up to 40 months.)
- Time above range (TAR)(From medication randomization till 2 years postpartum, up to 40 months.)
- Large-for-gestational-age at birth(At delivery)
- Hypoglycemia(<24 hours after birth)
- Hypertensive disorder of pregnancy(Randomization to delivery)
- Requiring mechanical ventilation(<72 hours after birth)
- Prediabetes(From delivery to 2 years postpartum)
- Impaired fasting glucose (IFG)(From delivery to 2 years postpartum.)
- Hypertension(2 years postpartum)
- Respiratory distress syndrome(Anytime during the first 72 hours after birth)
- Type 2 diabetes (T2D)(From delivery to 2 years postpartum)
- Treatment supplementation(From randomization to delivery)
- Impaired glucose tolerance (IGT)(From delivery to 2 years postpartum)
- Obesity overall and by class(2 years postpartum)
- Cholesterol(2 years postpartum)
- Mean glucose(From medication randomization till 2 years postpartum, up to 40 months.)
研究者
Kartik K Venkatesh
Associate Professor
Ohio State University