Comparison of the Therapeutic Effects of VR and VR + Metformin in the Treatment of Cesarean Section Scar Defect

Study Overview
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Brief Summary
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Cesarean section scar defect (CSD) is a novel recognized cause of postmenstrual abnormal uterine bleeding in women. No clinical guidelines have been issued for the management of CSD. The investigators have previously demonstrated that vaginal repair of CSD was an relative effective treatment of CSD. However, only 28.2% of the CSD patients normalized to less than 7 days of menstruation, whereas 51.2% of women had 7 to 10 days of menstruation at 6 months post vaginal repair. The previous research suggested that the occurrence of CSD may be related to the aging phenotype of the myometrium. Metformin, as a classic diabetes treatment drug, has an important position in anti-aging therapy. Therefore, the randomized study was designed to evaluate whether the application of metformin in combination with vaginal repair could achieve better clinical effects than those achieved by vaginal CSD repair alone.

Detailed Description
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The previous research suggested that the occurrence of cesarean section scar defect (CSD) may be related to the aging phenotype of the myometrium. The aging of the myometrium in some cesarean section patients reduces the proliferation and repair of smooth muscle cells and endometrial cells to a certain extent. The prognosis of vaginal repair is poor and the repair of the endometrium during menstruation is not good. Metformin, as a classic diabetes treatment drug, has an important position in anti-aging therapy. Its research and application range is the widest, and significant results have been achieved in a number of clinical trials. At the same time, its side effects are less than other anti-aging drugs, and the patient adaptability is better. It maybe the best choice for the treatment of anti-aging diseases. Therefore, the randomized study was designed to evaluate whether the application of metformin in combination with vaginal repair could achieve better clinical effects than those achieved by vaginal CSD repair alone.

Official Title
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Comparison of the Therapeutic Effects of Vaginal Repair and Vaginal Repair + Metformin in the Treatment of Cesarean Section Scar Defect

Conditions
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Defect

Intervention / Treatment
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* Drug: Metformin Hydrochloride Sustained-release Tablets
* Procedure: Vaginal repair


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients are younger than 40 and over the age of 18. Clearly diagnosed with CSD. Experiencing clinical features of abnormal uterine bleeding, prolonged menstrual flow (the duration of menstruation is more than 10 days). The thickness of the remaining muscular layer of CSD was less than 3 mm. Normal range of blood sugar and insulin No serious medical problems (important viscera function in the normal range). No uterine fibroids, endometriosis, adenomyosis No malignant tumors. Sign the informed consent. Exclusion Criteria: Over the age of 40 or younger than 18; Indefinite diagnosis. Malignant tumors. With severe medical problems (severe liver disease, kidney disease, respiratory diseases, heart disease or uncontrolled diabetes, epilepsy, etc., dysfunction of important organs). Contraindications to metformin (baseline creatinine >124μmol/L, hypersensitivity to metformin, or a metabolic acidosis), use of drugs that might interact with metformin (glyburide, furosemide, or cationic drugs) Pregnant. Mental diseases. Unwilling to comply with the research plan.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: vaginal repair + metformin<br>CSD patients were treated with vaginal repair of CSD in combination with metformin (Boke, 500 mg, Wanhui Shuanghe, Beijing, China) as an oral medicine (abbreviated as VR + metformin). In the group of VR + metformin, the patients start oral metformin from one month before the operation to 6 months after the operation. The dose is 500mg twice a day. The detailed procedure of VR has been described in investigators' previous study. | Drug: Metformin Hydrochloride Sustained-release Tablets<br>* drug<br>* Other names: Boke;Procedure: Vaginal repair<br>* The procedure of vaginal repair of CSD was shown as following. The bladder was dissected away carefully from the uterus toward the abdominal cavity until the peritoneum was reached. The CSD tissue was cut to the normal healthy muscle after the abdominal cavity had been entered, and the lower uterine segments had been completely exposed. A double layer of 1-0 absorbable interrupted sutures was used to close the incisions.<br>|
| Active Comparator: vaginal repair<br>The procedure of vaginal repair of CSD was shown as following. The bladder was dissected away carefully from the uterus toward the abdominal cavity until the peritoneum was reached. The CSD tissue was cut to the normal healthy muscle after the abdominal cavity had been entered, and the lower uterine segments had been completely exposed. A double layer of 1-0 absorbable interrupted sutures was used to close the incisions. | Procedure: Vaginal repair<br>* The procedure of vaginal repair of CSD was shown as following. The bladder was dissected away carefully from the uterus toward the abdominal cavity until the peritoneum was reached. The CSD tissue was cut to the normal healthy muscle after the abdominal cavity had been entered, and the lower uterine segments had been completely exposed. A double layer of 1-0 absorbable interrupted sutures was used to close the incisions.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| thickness of the remaining muscular layer (TRM) (mm) | The thickness of the remaining muscular layer is measured by magnetic resonance imaging (MRI) | 12 weeks after vaginal repair of CSD | 
| Duration of menstruation (day) | Duration of menstruation (day) | 12 weeks after vaginal repair of CSD | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| thickness of the remaining muscular layer (TRM) (mm) | The thickness of the remaining muscular layer is measured by MRI | 24 weeks after vaginal repair of CSD | 
| Duration of menstruation (day) | Duration of menstruation (day) | 24 weeks after vaginal repair of CSD | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metformin, cesarean section scar defect