Metformin for Preeclampsia Prevention in Pregnant Women With Type 1 Diabetes Mellitus

Although major advancements have been made in improving glycemic management in type 1 diabetes mellitus (DM), women entering pregnancy with type 1 DM continue to be at dramatically increased risk for adverse maternal and neonatal outcomes, including hypertensive disorders of pregnancy (HDP). At present, there is a lack of effective preventive interventions for HDP, which are associated with significant maternal and neonatal morbidity and mortality. Clinical and in vitro data have shown promise for metformin in prevention of HDP in non-diabetic women. Metformin has a reassuring fetal safety profile and has been well studied in type 1 DM outside of pregnancy. The hypothesis to be tested in this application is that compared to usual care, daily oral metformin therapy initiated prior to 20 weeks' gestation in women with type 1 DM reduces the frequency of HDP.

Study Overview

• Status: Recruiting
• Conditions: Diabetes Mellitus, Type 1; Pregnancy in Diabetes
• Intervention / Treatment: Drug: Metformin

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Maisa N Feghali, MD; Phone Number: 4126471000; Email: feghalim@upmc.edu

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Recruiting
      • Magee Womens Hospital of UPMC
      • Principal Investigator: Maisa Feghali, MD
      • Contact: Maisa Feghali, MD; Phone Number: 412-647-1000; Email: feghalim@upmc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Pregnant women 18-50 years
• 12 0/7 and 19 6/7 weeks of gestation
• Diagnosed with type 1 DM prior to pregnancy.

Exclusion Criteria:

• Known allergy or adverse reaction to metformin
• Multiple gestation
• Abnormal obstetrical ultrasound suspicious for major congenital abnormality, known or suspected fetal aneuploidy
• Medical comorbidities that increase risk for metformin use: renal insufficiency (creatinine > 1.1 mg/dL), proteinuria (P:C >0.3 or 24-hour urine protein > 300 mg), active liver disease (acute hepatitis, chronic active hepatitis, persistently abnormal liver enzymes 3x above normal), inflammatory bowel disease (Crohn's and Ulcerative colitis), major hematologic disorder (including alloimmune and isoimmune thrombocytopenia).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Usual care
Experimental: Metformin	Drug: Metformin; Participants randomized to metformin will receive metformin in addition to standard treatment of diabetes during pregnancy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Rate of hypertensive disorders of pregnancy	Delivery/End of pregnancy

Secondary Outcome Measures

Outcome Measure	Time Frame
Home glucose levels throughout pregnancy	Weekly, throughout pregnancy from enrollment to delivery
Birthweight	Delivery/End of pregnancy
Neonatal morbidity	Delivery/End of pregnancy

Other Outcome Measures

Outcome Measure	Time Frame
Gestational weight gain	At time of prenatal visits, throughout pregnancy from enrollment to delivery
Umbilical cord c-peptide	Delivery/End of pregnancy
Umbilical cord glucose	Delivery/End of pregnancy
Neonatal body composition	Delivery/End of pregnancy

Collaborators and Investigators

• Sponsor: Maisa N. Feghali, MD
• Investigators: Principal Investigator: Maisa N Feghali, MD, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): July 8, 2019
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: June 15, 2018
• First Submitted That Met QC Criteria: June 26, 2018
• First Posted (Actual): June 27, 2018

Study Record Updates

• Last Update Posted (Actual): October 12, 2023
• Last Update Submitted That Met QC Criteria: October 11, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Pregnancy Complications; Hypertension, Pregnancy-Induced; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Pre-Eclampsia; Pregnancy in Diabetics; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: PRO18050459

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No