Metformin to Prevent Preterm Birth in Twin Pregnancy

Preterm Birth Clinical Trial

— TwinMet  

Official title:

A Randomized Double Blinded Controlled Trial of Using Metformin to Prevent Preterm Birth in Twin Pregnancy

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05412056
• Other study ID #: UW 20-315
• Status: Not yet recruiting
• Phase: Phase 2/Phase 3
• Start date: June 2022
• Est. completion date: June 2025

Study information

• Verified date: June 2022
• Source: The University of Hong Kong
• Contact: Mimi Tin-yan Seto, MRCOG
• Phone: (852)22554647
• Email: mimiseto[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 790
• Est. completion date: June 2025
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Drug Effect
• Metformin
• Obstetric Labor, Premature
• Pregnancy Complications
• Pregnancy Preterm
• Premature Birth
• Premature Obstetric Labor
• Preterm Birth
• Twin; Complicating Pregnancy

Intervention

Drug:
• Metformin
as in arm/group description
• Placebo oral tablet
as in arm/group description

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
The University of Hong Kong

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Preterm birth	Number of participants with preterm birth	before 34+0 gestational weeks
Secondary	Preterm birth	Number of participants with preterm birth	before 32+0 weeks
Secondary	Preterm birth	Number of participants with preterm birth	before 28+0 weeks