Metformin + Esomeprazole for Pre-eclampsia

Overseen By Marwan Ma'ayeh, MD

Age: 18 - 65

Sex: Female

Trial Phase: Phase 1

Sponsor: Christiana Care Health Services

Must not be taking: Metformin, Esomeprazole, Glyburide, others

Disqualifiers: Diabetes, Metabolic acidosis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: Until delivery

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining metformin and esomeprazole (a medication commonly used to reduce stomach acid) can help women with pre-eclampsia safely extend their pregnancy. Pre-eclampsia is a pregnancy condition characterized by high blood pressure and potential organ damage. Previous studies showed that metformin alone might help prolong pregnancy, and researchers now aim to determine if adding esomeprazole improves outcomes. Women between 24 and 31 weeks pregnant with pre-eclampsia, who are managing their condition without needing immediate delivery, might be suitable candidates. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are already taking metformin or certain drugs that interact with it, like glyburide or furosemide.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that metformin is generally safe during pregnancy. It has been tested in pregnant women with diabetes, and these studies did not find a higher risk of pre-eclampsia, a type of high blood pressure during pregnancy. Specifically, one study found that extended-release metformin might help extend pregnancy in women with early pre-eclampsia.

Esomeprazole, a drug that reduces stomach acid, has also been used during pregnancy. Although it isn't directly linked to treating pre-eclampsia, it has been used safely in pregnant women.

Researchers are studying the combination of metformin and esomeprazole to see if it can better manage pre-eclampsia by targeting specific markers in the body. Early research on these drugs individually suggests they are well-tolerated, but current studies are examining their combined safety. Since this trial is in its early stages, the main focus is on safety, and participants will be closely monitored for any side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for pre-eclampsia, which typically involve blood pressure medications and close monitoring, the combination of metformin and esomeprazole offers a novel approach. Metformin, commonly used for diabetes, may help address insulin resistance, a factor thought to contribute to pre-eclampsia. Esomeprazole, a proton pump inhibitor, adds an anti-inflammatory component, potentially reducing oxidative stress, which is also linked to the condition. Researchers are excited because this combination targets underlying metabolic and inflammatory pathways, offering a potential new strategy to improve outcomes for pregnant women with pre-eclampsia.

What evidence suggests that this trial's treatments could be effective for pre-eclampsia?

This trial will evaluate the combination of metformin and esomeprazole for treating pre-eclampsia. Research has shown that using these drugs together might help treat pre-eclampsia. In a previous study, metformin reduced the risk of pre-eclampsia in obese women from 11% to 3%. Both metformin and esomeprazole reduce harmful substances from the placenta and improve blood vessel function. This combination might be more effective than using each drug alone. While these results are promising, further research is needed to confirm them. ^{2 3 5 6 7}

Who Is on the Research Team?

Matthew Hoffman, MD

Principal Investigator

ChristianaCare

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

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

I am a woman aged 18 or older.

I am advised to wait for natural labor without any medical reason for immediate delivery.

Exclusion Criteria

Maternal or fetal compromise that necessitated immediate delivery

Hypersensitivity to metformin or esomeprazole

Metabolic acidosis

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive combination metformin and esomeprazole until delivery

Until delivery

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Esomeprazole
• Metformin
• Placebo

Trial Overview 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.

How Is the Trial Designed?

Group I: combination metformin and esomeprazole Experimental Treatment 1 Intervention

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

Group II: expectant management Active Control 1 Intervention

Metformin is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Glucophage for:

• Type 2 diabetes

Approved in United States as Glucophage for:

• Type 2 diabetes

Approved in Canada as Glucophage for:

• Type 2 diabetes

Approved in Japan as Glucophage for:

• Type 2 diabetes

Approved in China as Glucophage for:

• Type 2 diabetes

Approved in Switzerland as Glucophage for:

• Type 2 diabetes

Who Is Running the Clinical Trial?

Christiana Care Health Services

Lead Sponsor

Trials

118

Recruited

204,000+

Published Research Related to This Trial

The PI2 Trial is a phase II clinical study involving 150 women with preterm pre-eclampsia, testing the efficacy of extended-release metformin compared to a placebo, with the primary goal of delaying delivery by at least 5 days.

Metformin is already known to be safe during pregnancy and may provide a new therapeutic option to manage preterm pre-eclampsia, potentially improving outcomes for both mothers and their babies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double blind, randomised, placebo-controlled trial to evaluate the efficacy of metformin to treat preterm pre-eclampsia (PI2 Trial): study protocol. Cluver, C., Walker, SP., Mol, BW., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5821305/

Combining metformin and esomeprazole is additive in ... One trial showed as a secondary outcome that the incidence of preeclampsia was reduced in obese women taking metformin from 11 to 3%, while a ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03717701?cond=%22Eclampsia%22&intr=%22Metformin%22&viewType=Table&rank=3

Metformin and Esomeprazole in Treatment of Early Onset ... Data collected at the beginning of a clinical study for all participants and for each arm or comparison group. These data include demographics, such as age, sex ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/29466360/

Combining metformin and esomeprazole is additive in ... The combination of metformin and esomeprazole may provide a more effective treatment or prevention for preeclampsia compared to either as single agents.

4. withpower.com withpower.com/trial/phase-1-eclampsia-3-2022-58e49

Metformin + Esomeprazole for Pre-eclampsia This follows evidence that both drugs may reduce harmful substances from the placenta and improve blood vessel function.

5. bpspubs.onlinelibrary.wiley.com bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/bcp.15416

Population pharmacokinetics of esomeprazole in patients with ... We used data from 10 pregnant participants with preterm preeclampsia, and. 49 non-pregnant participants to develop a population pharmacokinetic ...

6. trial.medpath.com trial.medpath.com/clinical-trial/35fcababb3baf108/use-metformin-esomeprazole-preterm-eclampsia

Metformin and Esomeprazole For Preterm Pre-eclampsia Investigators found that extended release metformin (3g daily) can prolong gestation in women with preterm pre-eclampsia. Combination metformin and esomeprazole ...

7. bmcmedicine.biomedcentral.com bmcmedicine.biomedcentral.com/articles/10.1186/s12916-024-03628-0

Metformin use and preeclampsia risk in women with diabetes Metformin in pregnancy was not associated with an altered risk of preeclampsia (RR 1.07 [95% CI 0.90–1.28]; aRR 1.00 [95% CI 0.72–1.39]; 9.1% vs ...