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Metformin for Hyperemesis Gravidarum Risk Reduction

This study is investigating if a daily oral medication called metformin extended-release (metformin-XR) can reduce the risk and severity of Hyperemesis Gravidarum (HG), which is severe nausea and vomiting during pregnancy. You might be able to join if you are a woman between 18 and 49 years old, have experienced HG in a previous pregnancy (meaning you needed IV fluids), and are currently trying to get pregnant. The researchers want to see if metformin-XR is safe and well-tolerated, and if it helps prevent HG from returning. They will measure how well you stick to the medication, any side effects, and if HG recurs and how severe it is during your pregnancy.

Study design
This is an interventional study planning to enroll 224 participants. Participants in the treatment arm will receive metformin-XR.
What's involved
You would take metformin-XR daily, starting before conception and gradually increasing the dose over 8 weeks. You would also use birth control until you reach your maintenance dose of metformin-XR.
Compensation
Not stated in the trial record.
Follow-up
Your adherence, tolerability, and safety will be measured from the start of treatment up to 12 months, or 2 weeks after confirmed pregnancy. HG recurrence and severity will be measured from confirmed pregnancy through 12 weeks of gestation.

AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.

NCT07129473

Hyperemesis Gravidarum Risk Reduction With Metformin

Recruiting
PHASE1Ages 18–49InterventionalPrevention
University of Southern California
~224 participants
Updated 2026-07-22 on ClinicalTrials.gov
What's tested:Metformin Extended Release Oral Tablet

At a glance

Recruiting sites
1 of 2 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Adherence to Escalating Doses of Metformin-XR
Measured over Baseline to 8 weeks after treatment initiation
+13 more outcomes measured

Conditions

Hyperemesis Gravidarum

Explore related trials

Hyperemesis Gravidarum

Where it's being run

2 sites across 2 states
Alabama1
California1

Study leadership

  • Marlena Fejzo, PhD · PRINCIPAL_INVESTIGATOR · University of Southern California

Who to contact

Marlena Fejzo, PhD
[email protected]
310-383-3581
Email the study team

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Do you actually qualify for this trial?

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Eligibility criteria

Inclusion

Ages 18-49
HG in prior pregnancy (clinical criteria: intravenous (IV) fluid treatment)
Trying to conceive
Treatment Arm: willing to refrain from trying to conceive during their metformin dose titration period and before 2 weeks at maximum tolerated dose (up to 8 weeks total). Will use birth control or contraceptive device until maintenance dose.
Under care of a personal OB/GYN or willing to establish care with a personal OB/GYN before study start
Ownership of a personal scale (or willingness to obtain one for study use)
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 to mildly decreased creatinine levels (estimated GFR \> 60 mL/min/1.73m²)
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.
English speaking
Regular cycles

Exclusion

Allergic or adverse reaction to metformin-XR
Thalassemia
Cirrhosis and/or hepatic impairment
Decompensated heart failure
Daily/regular use of medications/substances (tobacco, cyclobenzaprine, cannabis, escitalopram, sertraline, other SSRIs, Lasix)
Treatment Arm: Use of insulin, sulfonylureas, meglitinides, or other blood sugar altering medication
Assisted Reproductive Technology
Excess alcohol consumption (\> 7 standard drinks per week on average)
Pregnant
Not trying to conceive
Treatment Arm: Residing outside California/Alabama
Treatment Arm: abnormal blood panel (CBC) (e.g., white count or platelets not within the normal range)
Treatment Arm: abnormal creatinine levels (estimated GFR \< 60 mL/min/1.73m² excluded from the study, signs of kidney disease)
Treatment Arm: current metformin use
Survey/Comparator Arm: current metformin use or plans to take metformin prior to pregnancy
Any medical/surgical condition that the investigator feels would compromise the participant's participation in the study
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.
Not english speaking
Irregular cycles
Not willing to refrain from trying to conceive/use birth control or contraceptive device until maintenance dose.

What this trial measures

  • Adherence to Escalating Doses of Metformin-XRBaseline 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-XRBaseline through treatment completion (up to 12 months after maintenance dose following cessation of birth control/contraceptive device 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.

  • Hyperemesis Gravidarum (HG) Recurrence and SeverityFrom 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.

  • Pregnancy & Neonatal Outcomes: Incidence of Pregnancy ComplicationsFrom confirmed pregnancy through delivery

    Proportion of participants who experience predefined pregnancy complications (e.g., gestational diabetes, preeclampsia, gestational hypertension). Data will be abstracted from medical records and study surveys.

  • Pregnancy & Neonatal Outcomes: Delivery CharacteristicsAt delivery

    Proportion of participants with a favorable delivery outcome, defined as live birth at ≥37 weeks gestation. Delivery outcome will be abstracted from medical records and study surveys.

  • Pregnancy & Neonatal Outcomes: Assessment of Peripartum EventsFrom confirmed pregnancy to 6 months postpartum

    Peripartum events will be evaluated using the validated Peripartum Events Scale (PES). PES score will be evaluated via medical record abstraction. The lowest possible PES score is zero, with higher scores corresponding to more stressful labor and delivery experiences.

  • Pregnancy & Neonatal Outcomes: Maternal Postpartum DepressionFrom birth to 6 months postpartum

    Maternal mental health will be assessed using the Edinburgh Postnatal Depression Scale (EPDS). The EPDS range is 0-30, with higher scores corresponding to more severe depressive symptoms.

  • Pregnancy & Neonatal Outcomes: Maternal Postpartum AnxietyFrom birth to 6 months postpartum

    Maternal mental health will be assessed using the Postpartum-Specific Anxiety Scale (PSAS). The PSAS range is 51-204, with higher scores corresponding to greater postpartum-specific anxiety.

  • Pregnancy & Neonatal Outcomes: Maternal Postpartum Quality of LifeFrom birth to 6 months postpartum

    Maternal postpartum quality of life will be assessed using the validated Maternal Postpartum Quality of Life (MAPP-QOL) Questionnaire. The MAPP-QOL possible total score range is 38-228, with higher scores corresponding to better quality of life.

  • Pregnancy & Neonatal Outcomes: Neonatal Health StatusAt delivery

    Proportion of neonates who experience an adverse neonatal outcome, defined as the presence of at least one predefined adverse neonatal event, including but not limited to low birth weight (\<2500 grams), preterm birth (\<37 weeks gestation), admission to a neonatal intensive care unit (NICU), or low 5-minute Apgar score (\<7). Data will be obtained from medical record abstraction and study surveys.

  • Pregnancy & Neonatal Outcomes: Child Developmental StatusFrom birth to 6 months postpartum (with optional follow up until the end of the 5-year study period)

    Child development will be assessed before 6 months postpartum using the validated Ages and Stages Questionnaires, Third Edition (ASQ-3). Optionally, every 6 months up to year 5 (study completion), participants will have the opportunity to complete an additional ASQ-3 assessment corresponding to their child's age to report long-term child outcomes.

  • Indicators of Metformin Response: Genetic FactorsOnce at baseline

    Genotyping of variants associated with HG risk (e.g., rs1058587/GDF15, rs9312688/IGFBP7, rs12790159/PGR, and rs10948901/GFRAL) to explore their association with metformin response and pregnancy outcomes.

  • Indicators of Metformin Response: Circulating Biomarker LevelsOnce 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 biomarker (e.g., GDF15, IGFBP7) concentrations at three timepoints in the Treatment Arm (baseline, after dose escalation, and during early pregnancy) to explore the role of each as a predictive biomarker for HG and metformin response.

  • Indicators of Metformin Response: Demographic CharacteristicsAt baseline

    Demographic information will be collected via initial study survey and qualitatively analyzed for associations with HG and metformin response.