Hyperemesis Gravidarum Risk Reduction With Metformin

Обзор

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

Вмешательства

• Препарат Metformin Extended Release Oral Tablet
  Participants 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

Первичные конечные точки

• Adherence to Escalating Doses of Metformin-XR [Срок оценки: Baseline to 8 weeks after treatment initiation]
• Tolerability and Safety of Metformin-XR [Срок оценки: 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)]
• Hyperemesis Gravidarum (HG) Recurrence and Severity [Срок оценки: From confirmed pregnancy through 12 weeks of gestation]
• Pregnancy & Neonatal Outcomes: Incidence of Pregnancy Complications [Срок оценки: From confirmed pregnancy through delivery]
• Pregnancy & Neonatal Outcomes: Delivery Characteristics [Срок оценки: At delivery]
• Pregnancy & Neonatal Outcomes: Assessment of Peripartum Events [Срок оценки: From confirmed pregnancy to 6 months postpartum]
• Pregnancy & Neonatal Outcomes: Maternal Postpartum Depression [Срок оценки: From birth to 6 months postpartum]
• Pregnancy & Neonatal Outcomes: Maternal Postpartum Anxiety [Срок оценки: From birth to 6 months postpartum]
• Pregnancy & Neonatal Outcomes: Maternal Postpartum Quality of Life [Срок оценки: From birth to 6 months postpartum]
• Pregnancy & Neonatal Outcomes: Neonatal Health Status [Срок оценки: At delivery]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Профилактика

Центры проведения

США · 2 центра

• The Morning Sickness & HG Clinic — Birmingham
• University of Southern California - Keck School of Medicine — Los Angeles

Публикации

• Fejzo M, Rocha N, Cimino I, Lockhart SM, Petry CJ, Kay RG, Burling K, Barker P, George AL, Yasara N, Premawardhena A, Gong S, Cook E, Rimmington D, Rainbow K, Withers DJ, Cortessis V, Mullin PM, MacGibbon KW, Jin E, Kam A, Campbell A, Polasek O, Tzoneva G, Gribble FM, Yeo GSH, Lam BYH, Saudek V, Hughes IA, Ong KK, Perry JRB, Sutton Cole A, Baumgarten M, Welsh P, Sattar N, Smith GCS, Charnock-Jones PMID 38092039
• Sharma N, MacGibbon KW, Brecht-Doscher A, Cortessis VK, Fejzo MS. Prepregnancy metformin use associated with lower risk of severe nausea and vomiting of pregnancy and hyperemesis gravidarum. Am J Obstet Gynecol. 2025 Dec;233(6):649.e1-649.e14. doi: 10.1016/j.ajog.2025.06.055. Epub 2025 Jun 28. PMID 40588059

Идентификаторы

NCT: NCT07129473 · APP-25-03192

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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