Effect of Metformin on Healthy Live Birth in Women With Prediabetes

NCT06064669 | Recruiting DMC

• 1 other identifier: MELT-PreDM
• Study Type: interventional
• Target: 988
• Locations: 1 country
• Sites: 1

Brief Summary

To evaluate the efficacy and safety of metformin pretreatment on reproductive outcomes in infertile women with prediabetes.

Conditions

Metformin; Prediabetes; In-Vitro Fertilization

Outcome Measures

Primary Outcomes (1)

• healthy live birth

  defined as a singleton live birth at ≥37 weeks, with infant birth weight between 2500 and 4000g and without a major congenital anomaly.

  From the date of randomization until delivery after the first embryo transfer, up to 16 months

Secondary Outcomes (25)

• Change in BMI

  From the date of randomization until the establishment of clinical pregnancy after the first embryo transfer, up to 26 weeks

• Change in fasting glucose level

  From the date of randomization until the establishment of clinical pregnancy after the first embryo transfer, up to 26 weeks

• Change in fasting insulin level

  From the date of randomization until the establishment of clinical pregnancy after the first embryo transfer, up to 26 weeks

• Change in 2-h levels of glucose after 75-g OGTT

  From the date of randomization until the establishment of clinical pregnancy after the first embryo transfer, up to 26 weeks

• Change in 2-h levels of insulin after 75-g OGTT

  From the date of randomization until the establishment of clinical pregnancy after the first embryo transfer, up to 26 weeks

Study Arms (4)

Metformin-Metformin Group

EXPERIMENTAL

Metformin pretreatment before ovarian stimulation till oocyte retrieval and cryopreservation of all embryos, and followed by metformin pretreatment before endometrial preparation for frozen embryo transfer and till the establishment of clinical pregnancy (7-8 weeks gestation) after the first frozen embryo transfer.

Drug: Metformin pretreatment before ovarian stimulation; Drug: Metformin pretreatment before endometrial preparation for frozen embryo transfer

Metformin-Placebo Group

EXPERIMENTAL

Metformin pretreatment before ovarian stimulation till oocyte retrieval and cryopreservation of all embryos, and followed by placebo pretreatment before endometrial preparation for frozen embryo transfer and till the establishment of clinical pregnancy (7-8 weeks gestation) after the first frozen embryo transfer.

Drug: Metformin pretreatment before ovarian stimulation; Drug: Placebo pretreatment before endometrial preparation for frozen embryo transfer

Placebo-Metformin Group

EXPERIMENTAL

Placebo pretreatment before ovarian stimulation till oocyte retrieval and cryopreservation of all embryos, and followed by metformin pretreatment before endometrial preparation for frozen embryo transfer and till the establishment of clinical pregnancy (7-8 weeks gestation) after the first frozen embryo transfer.

Drug: Placebo pretreatment before ovarian stimulation; Drug: Metformin pretreatment before endometrial preparation for frozen embryo transfer

Placebo-Placebo Group

EXPERIMENTAL

Placebo pretreatment before ovarian stimulation till oocyte retrieval and cryopreservation of all embryos, and followed by placebo pretreatment before endometrial preparation for frozen embryo transfer and till the establishment of clinical pregnancy (7-8 weeks gestation) after the first frozen embryo transfer.

Drug: Placebo pretreatment before ovarian stimulation; Drug: Placebo pretreatment before endometrial preparation for frozen embryo transfer

Interventions

Metformin pretreatment before ovarian stimulation DRUG

The enrolled patients will be prescribed metformin 850mg twice daily for at least 4 weeks prior to ovarian stimulation till oocyte retrieval.

Also known as: Metformin before ovarian stimulation

Metformin-Metformin Group; Metformin-Placebo Group

Placebo pretreatment before ovarian stimulation DRUG

The enrolled patients will be prescribed placebo 850mg twice daily for at least 4 weeks prior to ovarian stimulation till oocyte retrieval.

Also known as: Placebo before ovarian stimulation

Placebo-Metformin Group; Placebo-Placebo Group

Metformin pretreatment before endometrial preparation for frozen embryo transfer DRUG

After oocyte retrieval, the enrolled patients will be prescribed metformin 850mg twice daily for at least 4 weeks before endometrial preparation for frozen embryo transfer and till the establishment of clinical pregnancy (7-8 weeks gestation) after the first frozen embryo transfer.

Also known as: Metformin before endometrial preparation

Metformin-Metformin Group; Placebo-Metformin Group

Placebo pretreatment before endometrial preparation for frozen embryo transfer DRUG

After oocyte retrieval, the enrolled patients will be prescribed placebo 850mg twice daily for at least 4 weeks before endometrial preparation for frozen embryo transfer and till the establishment of clinical pregnancy (7-8 weeks gestation) after the first frozen embryo transfer.

Also known as: Placebo before endometrial preparation

Metformin-Placebo Group; Placebo-Placebo Group

Eligibility Criteria

• Age: 20 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Women who are diagnosed with prediabetes by ADA criteria, including either IFG, IGT, or HbA1C 5.7-6.4%.
• Women aged 20-40 years.
• Women who plan to undergo a new cycle of IVF, ICSI, or PGT-A.

You may not qualify if:

• Women who are diagnosed with diabetes according to the ADA criteria11,12, which is meeting one of the following criteria: fasting plasma glucose ≥7.0mmol/L, 2-h plasma glucose during 75-g OGTT ≥11.1mmol/L, HbA1c≥6.5%, or a random plasma glucose≥11.1mmol/L.
• Women who are taking medicine that interfere with glucose metabolism, such as metformin, oral anti-diabetic agents (sulfonylureas, glinides, thiazolidinediones, α-glycosidase inhibitors, GLP-1 receptor agonist, etc.), weight loss drugs (i.e.orlistat, etc.), glucocorticoids, and growth hormones within 2 months before enrollment.
• Women with un-corrected hyperthyroidism or hypothyroidism.
• Women with congenital or acquired abnormal uterine cavity including septate uterus, unicornous uterus, uterus duplex, and intrauterine adhesions.
• Women with a diagnosis of adenomyosis.
• Women with untreated hydrosalpinx.
• Women who plan to undergo PGT-SR or PGT-M.
• Women with major medical comorbidities, such as known liver disease, known renal disease, or known significant anemia.

Sponsors & Collaborators

• Shandong University: lead
• Ren Ji Hospital of Shanghai Jiao Tong University: collaborator
• Women's Hospital of Zhejiang University: collaborator
• Shengjing Hospital: collaborator
• Nanjing Medical University: collaborator
• General Hospital of Ningxia Medical University: collaborator
• West China Second University Hospital: collaborator
• Maternal and Child Health Hospital of Henan Province: collaborator
• Qingdao women's and children's Hospital: collaborator

Study Sites (1)

Shandong University

Jinan, Shandong, China

RECRUITING

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MeSH Terms

Conditions

Prediabetic State

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Zi-Jiang Chen, Professor

  Shandong University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zi-Jiang Chen, Professor

CONTACT

+0086 531 85651190; chenzijiang@vip.163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Academician

Study Record Dates

• First Submitted: September 19, 2023
• First Posted: October 3, 2023
• Study Start: February 22, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: May 29, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: 6 months after publication
• Access Criteria: The data of this study are available on request from the corresponding author

Locations

CN (1)