NCT07129473

Hyperemesis Gravidarum Risk Reduction With Metformin

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 224 (estimated)
• Sponsor: University of Southern California · Academic / Other
• Sex: Female
• Age: 18 Years – 49 Years
• Healthy volunteers: Accepted

Summary

The goal of this clinical trial is to evaluate whether daily oral metformin extended-release (metformin-XR), taken prior to pregnancy, can reduce the risk and severity of Hyperemesis Gravidarum (HG)-a severe nausea and vomiting condition in pregnancy-in individuals aged 18-49 who have experienced HG in a previous pregnancy and are trying to conceive. Researchers also aim to better understand which individuals may respond well-or poorly-to metformin based on biological and clinical characteristics. The main questions this study aims to answer are: 1. Is metformin-XR acceptable and well-tolerated when taken by non-pregnant individuals who have had HG in a previous pregnancy and are currently trying to conceive? 2. How safe and tolerable is metformin-XR when taken at increasing doses over 8 weeks and continued through early pregnancy (or for up to 12 months if pregnancy does not occur)? 3. Among those who become pregnant during the study, does pre-pregnancy metformin-XR use reduce the risk of HG coming back and lower the severity of nausea and vomiting symptoms? 4. How does pre-pregnancy metformin-XR use affect pregnancy outcomes, postpartum health, and newborn health and development? 5. Are there specific genetic, biomarker, demographic, or clinical features that predict whether someone is likely to benefit from metformin-XR or experience side effects that lead them to stop taking it? Researchers will compare a metformin treatment group to a survey-only group (comparator) to see if metformin-XR is associated with improved outcomes, including reduced HG recurrence and better maternal and neonatal health indicators. Participants will: Complete online questionnaires before pregnancy, during early pregnancy, and postpartum (Treatment group only) Take daily metformin-XR and attend three brief study visits (Treatment group only) Undergo blood draws at specified timepoints to assess safety and biological response

Conditions

• Hyperemesis Gravidarum

Interventions

Type	Name	Description
DRUG	Metformin Extended Release Oral Tablet	Participants in the Treatment Arm will receive oral extended-release metformin (metformin-XR) 1x daily with an evening meal starting prior to conception. Daily dosing will begin at 500 mg and increase gradually over an 8 week period (+500mg every 2 weeks, as tolerated) to a maximum tolerated dose of up to 2,000 mg. Treatment at highest tolerated dose will continue until either 2 weeks after a positive pregnancy test or 12 months from treatment start, whichever comes first. Participants will attend 3 clinic visits and provide blood samples at baseline, after dose escalation, and during early pregnancy to assess biomarker levels and genetic characteristics. Daily dosing, adherence, and side effects are recorded via MyCap; clinical visits include vital signs, PUQE-24/HELP scores, and blood draws (CBC, creatinine, genotyping, biomarker levels). Postpartum surveys include a metformin treatment \& HG outcomes survey (REDCap) and additional measures (PES, MAPP-QOL, EPDS, PSAS, and ASQ-3).

Timeline

• Start date: 2026-01-01
• Primary completion: 2030-01-01
• Completion: 2031-01-01
• First posted: 2025-08-19
• Last updated: 2025-12-11

Regulatory

• FDA-regulated drug study