Hyperemesis Gravidarum Risk Reduction With Metformin

Not Applicable

Not yet recruiting

• Conditions: Hyperemesis Gravidarum
• Interventions: Drug: Metformin Extended Release Oral Tablet

• Registration Number: NCT07129473
• Lead Sponsor: University of Southern California

Brief 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.

The main questions it aims to answer are:

Is metformin-XR acceptable and well-tolerated when taken by non-pregnant individuals trying to conceive?

Does pre-pregnancy metformin-XR use reduce HG recurrence and symptom severity in a subsequent pregnancy?

Researchers will compare a metformin treatment group to a survey-only comparator group to see if metformin-XR is associated with improved outcomes, including lower recurrence of HG and better maternal and neonatal health indicators.

Participants will:

Complete online questionnaires before and during early pregnancy

(Treatment group only) Take daily metformin-XR and attend three brief study visits

(Treatment group only) Undergo blood draws for GDF15 and safety labs at specified timepoints

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-08
• Study First Submitted: 2025-08-07
• Study First Submitted QC: 2025-08-13
• Last Update Submitted: 2025-08-13
• Study First Posted: 2025-08-19
• Last Update Posted: 2025-08-19
• Study Start: 2025-10-01
• Primary Completion: 2029-10
• Study Completion: 2030-10-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Female
• Target Recruitment: 224

Inclusion Criteria

• Ages 18-49
• HG in prior pregnancy (clinical criteria: intravenous (IV) fluid treatment)
• Trying to conceive
• Willing to participate in a trial that includes daily use of an oral agent prior to pregnancy
• Treatment Arm: residing in California/Alabama
• Treatment Arm: normal blood panel (CBC) (e.g., white count, hemoglobin, platelets all within the normal range)
• Treatment Arm: normal creatinine levels (GFR < 45)
• Survey/Comparator Arm: not currently taking metformin and do not plan to take metformin prior to pregnancy
• Able and willing to provide written informed consent prior to initiation of any study procedures.
• Demonstrates understanding of the study objectives, requirements, potential risks, and willingness to comply with study procedures and follow-up.

Exclusion Criteria

• Allergic or adverse reaction to metformin-XR
• Chronic diseases/conditions
• Daily medications/substances (tobacco, cyclobenzaprine, cannabis, escitalopram, sertraline, other Selective Serotonin Reuptake Inhibitors (SSRIs))
• Assisted Reproductive Technology
• Pregnant
• Not trying to conceive
• Pre-existing kidney dysfunction
• Treatment Arm: Residing outside California/Alabama
• Anemia
• Treatment Arm: abnormal blood panel (CBC) (e.g., white count, hemoglobin, or platelets not within the normal range)
• Treatment Arm: abnormal creatinine levels (GFR > 45 excluded from the study, signs of kidney disease)
• Survey/Comparator Arm: current metformin use or plans to take metformin prior to pregnancy
• Not able and willing to provide written informed consent prior to initiation of any study procedures.
• Does not demonstrate understanding of the study objectives, requirements, potential risks, and willingness to comply with study procedures and follow-up.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment Arm	Metformin Extended Release Oral Tablet	Treatment Arm (N=112): * Individuals with a prior HG pregnancy with intravenous (IV) fluid treatment and current pregnancy intent * Residing in California or Alabama * Daily metformin-XR, escalated from 500 mg to 2000 mg as tolerated * Continue treatment until either 2 weeks post-pregnancy confirmation or up to 12 months

Primary Outcome Measures

Name	Time	Method
Adherence to escalating doses of metformin-XR	Baseline to 8 weeks after treatment initiation	Proportion of participants in the Treatment Arm who reach and maintain each target dose level during the 8-week dose-escalation period, as recorded via MyCap survey entries.
Tolerability and safety of metformin-XR	Baseline through treatment completion (up to 12 months after treatment initiation or 2 weeks after confirmed pregnancy, whichever comes first)	Number and severity of treatment-related adverse events and dose-limiting toxicities experienced by participants during the 8-week dose-escalation period and maintenance phase. Safety assessed by participant report, clinical evaluations, and laboratory results.

Secondary Outcome Measures

Name	Time	Method
Hyperemesis gravidarum (HG) recurrence and severity	From confirmed pregnancy through 12 weeks of gestation	Incidence and severity of HG in subsequent pregnancy, assessed using validated tools (Pregnancy-Unique Quantification of Emesis (PUQE-24), HyperEmesis Level Prediction (HELP)Score) and pregnancy experience survey responses.
Circulating GDF15 levels	Once at baseline, once when participant reaches highest tolerated metformin dose (up to week 8), and once at pregnancy confirmation in participants who conceive	Measurement of GDF15 concentrations at three timepoints in the Treatment Arm (baseline, after dose escalation, and during early pregnancy) to explore its role as a predictive biomarker for HG.
Maternal and neonatal outcomes	From confirmed pregnancy through delivery	Assessment of maternal weight gain, pregnancy complications, delivery outcomes, and neonatal health indicators via surveys and medical record abstraction.