What is the mechanism of action of this treatment?

Extended-release metformin, a common treatment for preterm birth, works by reducing the secretion of soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin from the placenta and endothelium. These factors are known to cause endothelial dysfunction, which is a key issue in preterm pre-eclampsia. By improving endothelial function, metformin helps to manage pre-eclampsia and can prolong gestation, thereby reducing the risk of preterm birth. This mechanism is crucial for preterm birth patients as it directly targets the underlying causes of pre-eclampsia, improving pregnancy outcomes.

What side effects are associated with this type of intervention?

Extended-release metformin, used in the treatment of preterm birth, commonly causes gastrointestinal side effects such as nausea, vomiting, diarrhea, and abdominal discomfort. There are also potential long-term concerns, including an increased risk of offspring being overweight. Other treatments for preterm birth may have similar gastrointestinal side effects and can also include risks related to metabolic and cardiovascular health.

What prior FDA approvals exist?

The FDA has approved several treatments for preterm birth, including progesterone supplements and corticosteroids. Progesterone, such as hydroxyprogesterone caproate, helps reduce the risk of preterm birth in women with a history of spontaneous preterm birth. Corticosteroids like betamethasone are used to accelerate fetal lung maturity when preterm birth is imminent. While these treatments do not specifically target placental and endothelial secretion of sFlt-1 and soluble endoglin, they play crucial roles in managing preterm birth risks. Extended-release metformin, currently under study, shows promise by addressing endothelial dysfunction, a different mechanism from the existing FDA-approved treatments.

What other types of research exist?

A promising novel alternative to extended-release metformin for preterm birth patients is the combination of metformin and esomeprazole. This combination has shown potential in reducing placental and endothelial secretion of sFlt-1 and soluble endoglin, and in reducing endothelial dysfunction.

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Metformin + Esomeprazole for Pre-eclampsia

Phase 1

Waitlist Available

Led By Matthew Hoffman, MD, MPH

Research Sponsored by Christiana Care Health Services

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Women with pre-eclampsia superimposed on chronic hypertension

Individuals presenting with pre-eclampsia between 24+0 and 31+6 weeks of gestation, with a single viable fetus and no major anomalies

Must not have

Diabetes or gestational diabetes currently on metformin therapy

Contraindications to metformin, esomeprazole

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tested a slow-releasing form of the medication metformin on pregnant women with early pre-eclampsia. The goal was to see if it could help prolong their pregnancies. The treatment works by lowering harmful substances that can cause blood vessel problems. Results showed that metformin could indeed help extend pregnancy duration in these women. Metformin has been studied for its potential to reduce the risk of pre-eclampsia and has shown promise in both preclinical and clinical studies.

Who is the study for?

This trial is for women over 18 with preterm pre-eclampsia between 24 and almost 32 weeks of pregnancy, carrying a single baby without major anomalies. It's not for those likely to deliver within 48 hours, with immediate delivery needs due to maternal or fetal issues, diabetes on metformin therapy, contraindications to the drugs being tested, certain kidney function levels, using interacting medications, multiple pregnancies, metabolic acidosis or allergies to the drugs.

What is being tested?

The study tests if Esomeprazole (20mg) combined with extended release Metformin can help prolong pregnancy in women with preterm pre-eclampsia. This follows evidence that both drugs may reduce harmful substances from the placenta and improve blood vessel function.

What are the potential side effects?

Potential side effects include digestive issues like nausea and diarrhea from Metformin; Esomeprazole might cause headaches or stomach pain. Both could potentially affect liver enzymes or vitamin B12 levels.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am a woman with worsening high blood pressure during pregnancy.

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I have pre-eclampsia and am between 24 and 32 weeks pregnant with one healthy baby.

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I have been diagnosed with preeclampsia.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I am currently taking metformin for my diabetes.

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I cannot take metformin or esomeprazole due to health reasons.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: combination metformin and esomeprazoleExperimental Treatment1 Intervention

Combination 2 g of oral extended release metformin, in divided doses and Esomeprazole 20mg daily until delivery.

Group II: expectant managementActive Control1 Intervention

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Esomeprazole 20mg

2022

Completed Phase 4

~990

0 / 5Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Extended-release metformin, a common treatment for preterm birth, works by reducing the secretion of soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin from the placenta and endothelium. These factors are known to cause endothelial dysfunction, which is a key issue in preterm pre-eclampsia. By improving endothelial function, metformin helps to manage pre-eclampsia and can prolong gestation, thereby reducing the risk of preterm birth. This mechanism is crucial for preterm birth patients as it directly targets the underlying causes of pre-eclampsia, improving pregnancy outcomes.

Loss of Akt increases soluble endoglin release from endothelial cells but not placenta.Heparin promotes soluble VEGF receptor expression in human placental villi to impair endothelial VEGF signaling.