search
Back to results

Metformin to Prevent Preterm Birth in Twin Pregnancy (TwinMet)

Primary Purpose

Preterm Birth, Premature Obstetric Labor, Twin; Complicating Pregnancy

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Metformin
Placebo oral tablet
Sponsored by
The University of Hong Kong
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Preterm Birth

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • All women age ≥ 18 years old
  • Viable twin pregnancy with dichorionic diamnioticity or monochorionic diamnioticity
  • Gestational age less than 20 completed weeks

Exclusion Criteria:

  • High order multiple pregnancy such as triplets or higher order multiple pregnancy with fetal reduction to twin pregnancy
  • Monochorionic monoamniotic twin pregnancy
  • Twin pregnancy with silent miscarriage of one twin
  • Excessive vaginal bleeding
  • Presence of congenital anomaly
  • Rupture of membranes
  • Congenital uterine anomaly
  • Unwillingness or inability to comply with study procedures
  • Known paternal or maternal abnormal karyotype
  • Known renal, liver, or heart failure
  • Pre-existing type 1 or 2 diabetes
  • Treatment with metformin at the time of screening
  • Allergic to metformin

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Active Comparator

    Placebo Comparator

    Arm Label

    Metformin

    Placebo

    Arm Description

    Metformin will be prescribed before 20 weeks to 33+6 weeks, started at a daily dose of 500mg in the first week, and the daily dose is increased by 500mg per week to a maximum of 2000mg in week 4 (1000mg twice per day). Women will be asked to take the maximum tolerated dose if they experience side effects from the medication.

    Placebo will be prescribed before 20 weeks to 33+6 weeks, started at a daily dose of 1 tablet in the first week, and the daily dose is increased by 1 tablet per week to a maximum of 4 tablets in week 4 (2 tablets twice per day). Women will be asked to take the maximum tolerated dose if they experience side effects from the medication.

    Outcomes

    Primary Outcome Measures

    Preterm birth
    Number of participants with preterm birth

    Secondary Outcome Measures

    Preterm birth
    Number of participants with preterm birth
    Preterm birth
    Number of participants with preterm birth

    Full Information

    First Posted
    June 6, 2022
    Last Updated
    June 17, 2022
    Sponsor
    The University of Hong Kong
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT05412056
    Brief Title
    Metformin to Prevent Preterm Birth in Twin Pregnancy
    Acronym
    TwinMet
    Official Title
    A Randomized Double Blinded Controlled Trial of Using Metformin to Prevent Preterm Birth in Twin Pregnancy
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    June 2022
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    June 2022 (Anticipated)
    Primary Completion Date
    June 2025 (Anticipated)
    Study Completion Date
    June 2025 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    The University of Hong Kong

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    No

    5. Study Description

    Brief Summary
    Preterm birth (PTB) is a major challenge to perinatal health. It accounts for 75% of perinatal deaths and more than 50% of long-term neurological disabilities. Neonates born preterm are also at risk of significant comorbidities, for example respiratory distress syndrome, chronic lung disease, retinopathy of prematurity, necrotizing enterocolitis, intraventricular haemorrhage and sepsis in the short term, as well as cerebral palsy, motor and sensory impairment, learning difficulties, and increased risk of chronic disease in long run. Twin pregnancy is associated with a higher risk of PTB when compared to singleton pregnancy. The National Vital Statistics reveals the PTB rate is 8.2% and 60.3% in singleton and twin pregnancy respectively in 2018. The mechanism of PTB in twin pregnancy is not completely understood and may be different from that of singleton pregnancy. At present, there are no good strategies to prevent PTB in twin pregnancy. In singleton pregnancy, metformin has been used for the treatment of gestational diabetes in pregnant women with obesity/ overweight or polycystic ovarian syndrome (PCOS). The rate of PTB of pregnant women with PCOS is significantly lower after using metformin. A decreasing trend of PTB is also noted after metformin use in obese pregnant women without PCOS. There is no study to investigate the effect of metformin in twin pregnancy. Premature uterine and amnion stretching in twin pregnancy can trigger preterm labour by increased prostaglandin synthesis and interleukin-1, activation of activator protein-1, expression of connexin-43 and stimulation of stretch dependent focal adhesion signaling. Inflammation is another risk factor for PTB. Metformin is an anti-inflammatory agent which can suppress inflammatory cytokines production and downregulate AMP-activated protein kinase medicated connexin-43 and nuclear factor κB activation. Anti-inflammatory actions of metformin can also reduce production of nitric oxide, prostaglandin E2 and pro-inflammatory cytokines through inhibition of NFκB activation in macrophages. Another possible mechanism to prevent PTB is the inhibition of mammalian target of rapamycin complex 1,which has a role in the timing of birth, by AMP-activated protein kinase. Therefore, metformin can be potentially used to prevent PTB in twin pregnancy. However, its effect in twin pregnancy has not been studied. The objective of the study is to determine if the use of metformin in twin pregnancy can prevent PTB.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Preterm Birth, Premature Obstetric Labor, Twin; Complicating Pregnancy, Pregnancy Complications, Pregnancy Preterm, Metformin, Drug Effect

    7. Study Design

    Primary Purpose
    Prevention
    Study Phase
    Phase 2, Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    790 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Metformin
    Arm Type
    Active Comparator
    Arm Description
    Metformin will be prescribed before 20 weeks to 33+6 weeks, started at a daily dose of 500mg in the first week, and the daily dose is increased by 500mg per week to a maximum of 2000mg in week 4 (1000mg twice per day). Women will be asked to take the maximum tolerated dose if they experience side effects from the medication.
    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    Placebo will be prescribed before 20 weeks to 33+6 weeks, started at a daily dose of 1 tablet in the first week, and the daily dose is increased by 1 tablet per week to a maximum of 4 tablets in week 4 (2 tablets twice per day). Women will be asked to take the maximum tolerated dose if they experience side effects from the medication.
    Intervention Type
    Drug
    Intervention Name(s)
    Metformin
    Intervention Description
    as in arm/group description
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo oral tablet
    Intervention Description
    as in arm/group description
    Primary Outcome Measure Information:
    Title
    Preterm birth
    Description
    Number of participants with preterm birth
    Time Frame
    before 34+0 gestational weeks
    Secondary Outcome Measure Information:
    Title
    Preterm birth
    Description
    Number of participants with preterm birth
    Time Frame
    before 32+0 weeks
    Title
    Preterm birth
    Description
    Number of participants with preterm birth
    Time Frame
    before 28+0 weeks

    10. Eligibility

    Sex
    Female
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: All women age ≥ 18 years old Viable twin pregnancy with dichorionic diamnioticity or monochorionic diamnioticity Gestational age less than 20 completed weeks Exclusion Criteria: High order multiple pregnancy such as triplets or higher order multiple pregnancy with fetal reduction to twin pregnancy Monochorionic monoamniotic twin pregnancy Twin pregnancy with silent miscarriage of one twin Excessive vaginal bleeding Presence of congenital anomaly Rupture of membranes Congenital uterine anomaly Unwillingness or inability to comply with study procedures Known paternal or maternal abnormal karyotype Known renal, liver, or heart failure Pre-existing type 1 or 2 diabetes Treatment with metformin at the time of screening Allergic to metformin
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Mimi Tin-yan Seto, MRCOG
    Phone
    (852)22554647
    Email
    mimiseto@gmail.com

    12. IPD Sharing Statement

    Learn more about this trial

    Metformin to Prevent Preterm Birth in Twin Pregnancy

    We'll reach out to this number within 24 hrs