Clinical trial NCT04523363: Metformin Versus Standard of Care Treatment in Pregnant Women With Prediabetes
Official title: Metformin Versus Standard of Care Treatment in Pregnant Women With Prediabetes: A Randomized Trial
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Prediabetes; Complicating Pregnancy
Keywords: maternal outcomes
neonatal outcomes
metformin
prediabetes
pregnancy
Lead sponsor: University of Massachusetts, Worcester
Sponsor class: OTHER
First posted: 2020-08-21
Enrollment: 0
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a prospective, single center, randomized study evaluating metformin in the treatment of pregnant women with prediabetes on maternal and neonatal outcomes.
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess if metformin reduces adverse outcomes associated with prediabetes in pregnancy. Our hypothesis is that pregnant women with prediabetes who are treated with metformin will show a greater reduction in large for gestational age infants at birth compared to women treated with the standard of care.

Detailed description: Women in pregnancy are routinely screened for diabetes in the first trimester and those who fall into the prediabetes category by hemoglobin A1c level of 5.7 to 6.4%, fasting plasma glucose of greater than or equal to 100 to 125, or oral glucose tolerance test of greater than or equal to 140 to less than 200 before 14 weeks gestation will be approached for consent in our randomized trial.

Once consent is obtained, the subjects will be randomized 1:1 into two parallel groups, the metformin treatment group and the standard of care treatment group (routine prenatal care). A random number generator will allocate the participants to the study groups.

Women taking metformin will continue twice daily dosing for the duration of their pregnancy after randomization. Those in the standard of care group will receive routine prenatal care. Both groups will undergo routine gestational diabetes testing by 28 weeks. Obstetric, maternal, and neonatal outcomes will then be assessed of both groups until the 6 week postpartum visit.

Eligibility criteria: Inclusion Criteria:

* Pregnant women with hemoglobin A1c of 5.7 to 6.4%, fasting plasma glucose of greater than or equal to 100 to 125, or oral glucose tolerance test of greater than or equal to 140 to less than 200 before 14 weeks gestation
* Pregnancy and delivery care obtained at University of Massachusetts (UMass) Memorial Medical Center
* Patients able to provide written informed consent

Exclusion Criteria:

* Pre-existing diabetes diagnosis as assessed at visit in the first trimester by history or by laboratory evaluation as listed above
* Presence of contra-indication to metformin (liver, renal, or heart failure) or sensitivity to metformin
* Participants who are under the age of 18
* Multiple Pregnancy
* Patients already taking metformin for other indications
* Fetal defect noted on early dating ultrasound
* Miscarriage before randomization

Primary outcomes:
measure: Birth Weight
timeFrame: At Birth
Secondary outcomes:
measure: Number of Participants needing Cesarean Section
timeFrame: At Delivery
measure: Number of Participants with Postpartum Hemorrhage
timeFrame: At Delivery
measure: Number of Participants with Development of Pregnancy Induced Hypertension
timeFrame: Through study completion, starting at 14 weeks until delivery
measure: Development of Gestational Diabetes
timeFrame: Assessed at 28 weeks of pregnancy
measure: Maternal Weight Gain in Pregnancy
timeFrame: At enrollment and last prenatal visit, starting at 14 weeks until delivery
measure: Pregnancy Outcome
timeFrame: Through study completion, starting at 14 weeks until delivery
measure: Number of Participants with Preterm birth
timeFrame: At delivery
measure: Neonatal Intensive Care Unit Admission
timeFrame: At delivery and within first 2 days of life
measure: Apgar Score at Birth
timeFrame: At delivery
measure: Number of Participants with Neonatal Birth Trauma
timeFrame: At Delivery
measure: Number of Participants with Shoulder Dystocia
timeFrame: At Delivery
measure: Number of Participants with Neonatal Hypoglycemia
timeFrame: Within first 2 days of life
measure: Number of Participants with Neonatal Respiratory Distress
timeFrame: At Delivery
measure: Number of Participants with Neonatal Hyperbilirubinemia
timeFrame: Within first 2 days of life
measure: Number of Participants requiring Neonatal Intubation
timeFrame: At Delivery
measure: Neonatal Cooling
timeFrame: Within first 2 days of life
measure: Umbilical Cord Blood Level of C-peptide
timeFrame: At Birth
measure: Umbilical Cord Blood Level of Leptin
timeFrame: At Birth
measure: Umbilical Cord Blood Level of Insulin
timeFrame: At Birth
measure: Placental Pathology
timeFrame: At Birth
Other outcomes:
Locations:
city: Worcester
country: United States
facility: University of Massachusetts Memorial Medical Center
state: Massachusetts
Study officials:
affiliation: UMass Memorial Health
name: Gianna L Wilkie, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Peterson C, Grosse SD, Li R, Sharma AJ, Razzaghi H, Herman WH, Gilboa SM. Preventable health and cost burden of adverse birth outcomes associated with pregestational diabetes in the United States. Am J Obstet Gynecol. 2015 Jan;212(1):74.e1-9. doi: 10.1016/j.ajog.2014.09.009. Epub 2014 Oct 28.
citation: Lawrence JM, Contreras R, Chen W, Sacks DA. Trends in the prevalence of preexisting diabetes and gestational diabetes mellitus among a racially/ethnically diverse population of pregnant women, 1999-2005. Diabetes Care. 2008 May;31(5):899-904. doi: 10.2337/dc07-2345. Epub 2008 Jan 25.
citation: Temple R, Murphy H. Type 2 diabetes in pregnancy - An increasing problem. Best Pract Res Clin Endocrinol Metab. 2010 Aug;24(4):591-603. doi: 10.1016/j.beem.2010.05.011.
citation: Lee AM, Fermin CR, Filipp SL, Gurka MJ, DeBoer MD. Examining trends in prediabetes and its relationship with the metabolic syndrome in US adolescents, 1999-2014. Acta Diabetol. 2017 Apr;54(4):373-381. doi: 10.1007/s00592-016-0958-6. Epub 2017 Jan 9.
citation: Chen L, Pocobelli G, Yu O, Shortreed SM, Osmundson SS, Fuller S, Wartko PD, Mcculloch D, Warwick S, Newton KM, Dublin S. Early Pregnancy Hemoglobin A1C and Pregnancy Outcomes: A Population-Based Study. Am J Perinatol. 2019 Aug;36(10):1045-1053. doi: 10.1055/s-0038-1675619. Epub 2018 Nov 30.
citation: Professional Practice Committee for the Standards of Medical Care in Diabetes-2016. Diabetes Care. 2016 Jan;39 Suppl 1:S107-8. doi: 10.2337/dc16-S018. No abstract available.