Hyperemesis Gravidarum Risk Reduction With Metformin
ConditionHyperemesis Gravidarum
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexFemale
Age18-49
SponsorUniversity of Southern California
About this trial
The goal of this clinical trial is to evaluate whether daily oral metformin extended-release (metformin-XR), taken prior to and in early 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 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 an 8-week titration period and continued through early pregnancy (or for up to 12 months after reaching maintenance dose 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, no study drug) 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
Eligibility criteria
This trial accepts healthy volunteersQualifiers
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.
Disqualifiers
Allergic or adverse reaction to metformin-XR
Thalassemia
Cirrhosis and/or hepatic impairment
Decompensated heart failure
Trial design
Design model
Parallel
Treatments tested in this trial
Metformin Extended Release Oral Tablet
DrugParticipants in the Treatment Arm will receive oral extended-release metformin (metformin-XR) once daily with an evening meal starting prior to conception. Daily dosing will begin at 500 mg and increase gradually over an 8-week period (+500 mg every 2 weeks, as tolerated, with increases, holds, or reductions based on symptom severity) to a maximum dose of 2,000 mg. Treatment at highest tolerated dose will continue until 2 weeks after positive pregnancy test or 12 months after cessation of birth control/contraceptive device. 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. Postpartum surveys include a metformin treatment \& HG outcomes survey (REDCap) and additional measures (PES, MAPP-QOL, EPDS, PSAS, and ASQ-3).
Treatment groups
224 Participants
are divided into 2 treatment groupsGroup A: Treatment ArmExperimental treatment 1 intervention
Group B: Survey/Comparator ArmNo intervention 0 interventions
Trial outcomes
Primary outcomes
1
Adherence to Escalating Doses of Metformin-XR
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.
Time frame
Baseline to 8 weeks after treatment initiation2
Tolerability and Safety of Metformin-XR
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.
Time frame
Baseline 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)3
Hyperemesis Gravidarum (HG) Recurrence and Severity
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.
Time frame
From confirmed pregnancy through 12 weeks of gestation4
Pregnancy & Neonatal Outcomes: Incidence of Pregnancy Complications
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.
Time frame
From confirmed pregnancy through deliverySponsors and contacts
Click on the lead sponsor to view all of their trials.
University of Southern California
Lead sponsor
The Morning Sickness & HG Clinic
Collaborator
Source ClinicalTrials.gov